Outcome of metastatic colorectal cancer: analysis of a consecutive series of 229 patients. The impact of a multidisciplinary approach.
New chemotherapy agents and integrated treatments have improved the prognosis of patients with metastatic colorectal cancer. From January 2000 to December 2002, 229 consecutive metastatic patients were prospectively followed and their outcomes were analyzed. They were divided initially into four treatment groups: A, palliative chemotherapy for extensive extrahepatic disease with or without hepatic disease (97 patients); B, palliative chemotherapy as in Group A for extensive hepatic disease unlikely to become resectable (36 patients); C, neoadjuvant chemotherapy for potentially resectable liver metastases if responsive to therapy (33 patients); D, immediate surgery for liver metastases (63 patients). The series was analyzed after a median follow-up of 22.6 months. The median progression-free survival was 9, 7.3, 11.5, and 26 months in Groups A, B, C, and D, respectively. The median overall survival was 20.1, 17.2, 24.8, and >48 months in Groups A, B, C, and D, respectively. The outcome was considered for the 69 patients with metastases confined to the liver (Groups B and C), who were treated initially with chemotherapy. Surgery was performed in 21 patients (5 from Group B, and 16 from Group C) and was R0 in 16. In resected patients, the median progression-free survival was 14.7 months and the median overall survival was 40.5 months. In unresected patients, the median progression-free survival was 7.6 months and the median overall survival was 17.5 months. Neoadjuvant therapy may prolong overall survival in a subset of patients with multiple hepatic metastases. The global impact on progression-free survival is low; less than one-half of the patients resected after chemotherapy are disease-free at three years. However, patients resected after chemotherapy obtained overall survival similar to that of primary surgery, suggesting a positive role for integrated approaches.


Induction of articular cartilage degradation by recombinant interleukin 1 alpha and 1 beta.
The purpose of this study was to compare the effects of human recombinant interleukin 1, alpha and beta, on articular cartilage. The effects of rIL-1 alpha and rIL-1 beta on proteoglycan degradation and synthesis following treatment of bovine articular cartilage in serum-free organ culture were quantified. Purified human IL-1 and both rIL-1 alpha and rIL-1 beta induced a two-fold or greater increase in glycosaminoglycan (GAG) release from cultured articular cartilage. Levels or rIL-1 alpha as low as 15 pM induced increased proteoglycan degradation whereas identical levels of rIL-1 beta did not. Killing of the cartilage cells abolished induced GAG release by all forms of IL-1. Analysis of proteoglycan size following IL-1 treatment showed limited degradation of material released into the culture medium or remaining within cartilage. Both forms of recombinant IL-1 inhibited GAG synthesis when continually present in the culture medium. Actinomycin D and cycloheximide inhibited IL-1 dependent cartilage destruction whereas indomethacin did not.


Sexually transmitted disease risk assessment used among low-risk populations in east central Africa: a review.
In sub-Saharan Africa where sexually transmitted diseases (STDs) are prevalent but health resources are scarce, algorithms that act as STD/HIV risk assessment (RA) tools for family planning (FP) and maternal/child health (MCH) clinic attenders may be useful. These RA algorithms generally comprise questions about a person's social, economic, demographic, behavioural and clinical background. The answers can be scored or scaled to indicate a higher probability of current STD/HIV infection and thus the need for testing or treatment. RA can be done alone, or can be combined with clinical examination where laboratory diagnosis is not feasible. But how accurate are RA tools? We reviewed six studies at African sites that examined the use of RA combined with a clinical algorithm for STD screening of clinic attendees. Researchers reported the standard measures of test accuracy: sensitivity (per cent of infected women found positive by the tool); specificity (per cent of uninfected women found negative by the tool), and positive predictive value (per cent of women found positive by the tool who are truly infected). Most algorithms had low sensitivity (< 50%) and low positive predictive value (< 20%). The addition of clinical examination, and of leucocyte esterase (LE) testing, improved accuracy. But algorithms that performed well in one site were less accurate at other sites. For illustrative purposes, we considered a hypothetical population of 1,000 women attending a FP clinic. With a prevalence of cervical gonorrhoea of five per cent, algorithm sensitivity of 40%, and algorithm specificity of 75%, the positive predictive value of the RA tool would be 7.7%. In other words, 20 (7.7%) women diagnosed as infected would actually have gonorrhoea, and 237 false positive women would be treated needlessly, with the attendant costs and risks. However, with a disease prevalence above 50%, as might prevail for vaginal infections, and the same sensitivity and specificity figures, the positive predictive value may reach 70-80%. Risk assessment appears to be a relatively easy way to integrate STD management into family planning and MCH practice. However, there is no evidence to show its effectiveness for screening low-risk populations. We urge improvement of these tools, including information on the behaviour of male partners, and addition of simple screening tests such as leucocyte esterase dipsticks.


Anisucoumaramide, a Bioactive Coumarin from Clausena anisum-olens.
A new coumarin, anisucoumaramide (1), and a new δ-truxinate derivative, anisumic acid (2), were isolated from Clausena anisum-olens. Their structures were elucidated from extensive NMR and MS data. The absolute configurations of the coumarins were assigned using the experimental and calculated electronic circular dichroism data. Anisucoumaramide (1) represents the first example of a naturally occurring coumarin of which the terpenoidal side chain does not comply with the biosynthesis isoprene rule due to the presence of an unprecedented acetamido motif directly connected with the terpenoidal side chain. The δ-truxinate derivative was isolated from Clausena species for the first time. Compound 1 showed high selectivity for the MAO-B isoenzyme and inhibitory activity in the nanomolar range. Putative biosynthesis pathways toward 1 and 2 are proposed.


Embedding of Genes Using Cancer Gene Expression Data: Biological Relevance and Potential Application on Biomarker Discovery.
Artificial neural networks (ANNs) have been utilized for classification and prediction task with remarkable accuracy. However, its implications for unsupervised data mining using molecular data is under-explored. We found that embedding can extract biologically relevant information from The Cancer Genome Atlas (TCGA) gene expression dataset by learning a vector representation through gene co-occurrence. Ground truth relationship, such as cancer types of the input sample and semantic meaning of genes, were showed to retain in the resulting entity matrices. We also demonstrated the interpretability and usage of these matrices in shortlisting candidates from a long gene list as in the case of immunotherapy response. 73 related genes are singled out while the relatedness of 55 genes with immune checkpoint proteins (PD-1, PD-L1, and CTLA-4) are supported by literature. 16 novel genes (ACAP1, C11orf45, CD79B, CFP, CLIC2, CMPK2, CXCR2P1, CYTIP, FER, MCTO1, MMP25, RASGEF1B, SLFN12, TBC1D10C, TRAF3IP3, TTC39B) related to immune checkpoint proteins were identified. Thus, this method is feasible to mine big volume of biological data, and embedding would be a valuable tool to discover novel knowledge from omics data. The resulting embedding matrices mined from TCGA gene expression data are interactively explorable online (http://bit.ly/tcga-embedding-cancer) and could serve as an informative reference for gene relatedness in the context of cancer and is readily applicable to biomarker discovery of any molecular targeted therapy.


Efficacy of laser in re-osseointegration of dental implants-a systematic review.
Despite their high success rates, peri-implantitis can affect the stability and function of dental implants. Various treatment modalities have been investigated for the treatment of peri-implantitis to achieve re-osseointegration. An electronic literature search was performed supplemented by a manual search to identify studies published until January 2022. Articles that evaluated re-osseointegration in peri-implantitis sites in animal models following laser therapy or antimicrobial photodynamic therapy (aPDT) were included. Case reports, case series, systematic reviews, and letters to the editor were excluded. Risk of bias and GRADE assessment were followed to evaluate the quality of the evidence. Six studies out of 26 articles identified on electronic search were included in this review. The studies included animal studies conducted on canine models. Four out of six studies reported a higher degree of re-osseointegration following treatment of implants with laser therapy. The findings suggest that laser decontamination shows potential in enhancing re-osseointegration, particularly with the Er: YAG laser, which effectively decontaminated implant surfaces. However, conflicting outcomes and limitations in the evidence quality warrant caution in drawing definitive conclusions. Based on the limited available evidence, laser therapy may show a higher degree of re-osseointegration of implants than mechanical debridement.


The clinical effectiveness of aspirin desensitization in chronic rhinosinusitis.
Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease characterized by chronic rhinosinusitis, nasal polyposis, asthma, and airway reactivity to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs). For patients who have inadequately controlled rhinosinusitis and/or asthma despite treatment with topical corticosteroids and leukotriene-modifying drugs, aspirin desensitization is an important therapeutic option. This review examines the evidence supporting the effectiveness of aspirin desensitization for the treatment of chronic rhinosinusitis in patients with AERD. Practical aspects of conducting safe aspirin desensitization procedures and optimizing therapeutic benefits are also reviewed. When conducted in accordance with current guidelines, aspirin desensitization is a safe procedure that allows patients with AERD who have an indication for aspirin or other NSAIDs to safely ingest these medications. There is now strong evidence that aspirin desensitization and daily aspirin therapy is effective for treatment of the chronic inflammatory disease of the upper airway and lower airways in AERD.


Soft neurological signs in childhood by measurement of arm movements using acceleration and angular velocity sensors.
Soft neurological signs (SNS) are evident in the motor performance of children and disappear as the child grows up. Therefore SNS are used as criteria for evaluating age-appropriate development of neurological function. The aim of this study was to quantify SNS during arm movement in childhood. In this study, we focused on pronation and supination, which are arm movements included in the SNS examination. Two hundred and twenty-three typically developing children aged 4-12 years (107 boys, 116 girls) and 18 adults aged 21-26 years (16 males, two females) participated in the experiment. To quantify SNS during pronation and supination, we calculated several evaluation index scores: bimanual symmetry, compliance, postural stability, motor speed and mirror movement. These index scores were evaluated using data obtained from sensors attached to the participants' hands and elbows. Each score increased as age increased. Results obtained using our system showed developmental changes that were consistent with criteria for SNS. We were able to successfully quantify SNS during pronation and supination. These results indicate that it may be possible to use our system as quantitative criteria for evaluating development of neurological function.


Mechanical Behavior of Elastic Self-Locking Nails for Intramedullary Fracture Fixation: A Numerical Analysis of Innovative Nail Designs.
Intramedullary nails constitute a viable alternative to extramedullary fixation devices; their use is growing in recent years, especially with reference to self-locking nails. Different designs are available, and it is not trivial to foresee the respective in vivo performances and to provide clinical indications in relation to the type of bone and fracture. In this work a numerical methodology was set up and validated in order to compare the mechanical behavior of two new nailing device concepts with one already used in clinic. In detail, three different nails were studied: (1) the Marchetti-Vicenzi's nail (MV1), (2) a revised concept of this device (MV2), and (3) a new Terzini-Putame's nail (TP) concept. Firstly, the mechanical behavior of the MV1 device was assessed through experimental loading tests employing a 3D-printed component aimed at reproducing the bone geometry inside which the device is implanted. In the next step, the respective numerical model was created, based on a multibody approach including flexible parts, and this model was validated against the previously obtained experimental results. Finally, numerical models of the MV2 and TP concepts were implemented and compared with the MV1 nail, focusing the attention on the response of all devices to compression, tension, bending, and torsion. A stability index (SI) was defined to quantify the mechanical stability provided to the nail-bone assembly by the elastic self-locking mechanism for the various loading conditions. In addition, results in terms of nail-bone assembly stiffness, computed from force/moment vs. displacement/rotation curves, were presented and discussed. Findings revealed that numerical models were able to provide good estimates of load vs. displacement curves. The TP nail concept proved to be able to generate a significantly higher SI (27 N for MV1 vs. 380 N for TP) and a greater stiffening action (up to a stiffness difference for bending load that ranges from 370 Nmm/° for MV1 to 1,532 Nmm/° for TP) than the other two devices which showed similar performances. On the whole, a demonstration was given of information which can be obtained from numerical simulations of expandable fixation devices.


Inhibition of enzymic incision of thymine dimers by covalently bound guanine adducts of 4-nitroquinoline-1-oxide in DNA.
The effects of the presence in DNA of covalently bound guanine adducts of the carcinogen 4-nitroquinoline-1-oxide on the pyrimidine dimer-DNA glycosylase, purified from bacteriophage T4-infected Escherichia coli, were investigated. E. coli DNA, labeled in thymine, photosensitized by silver nitrate, and irradiated by 254 nm monochromatic light, was the substrate. 4-Nitroquinoline-1-oxide was reduced to 4-hydroxyaminoquinoline-1-oxide and then reacted with irradiated DNA in the presence of seryl-AMP, yielding covalently bound adducts in DNA. These were assayed by high performance liquid chromatography. Enzyme activity was assayed by measuring release of labeled free thymine from directly photoreversed DNA after the reaction. Glycosylase activity was reduced against carcinogen-modified DNA, with the Vmax 38% of that against the control DNA; the Km was unaffected. Therefore, as with other modified purines, 4-nitroquinoline-1-oxide guanine modifications can reduce enzymic incision at thymine dimers. Left unrepaired, pyrimidine dimers are both mutagenic and carcinogenic. This is consistent with the possibility that interference with enzymic initiation of DNA excision repair of UV damage may be an indirect mechanism of mutagenesis by stable carcinogen-DNA adducts.


Examination of Psychosocial and Physiological Risk for Bulimic Symptoms in Youth With Type 1 Diabetes Transitioning to an Insulin Pump: A Pilot Study.
This study tested hypotheses drawn from a risk model positing that psychosocial risk plus disease-related and treatment factors contribute to bulimic symptoms in youth with type 1 diabetes (T1D) transitioning to an insulin pump. The goal of this study was to examine whether disease-related factors, particularly disease- and treatment-based disruption in hunger and satiety, contribute to report of bulimic symptoms in youth with T1D after accounting for psychosocial risk factors. 43 youth (ages 10-17, 54% female) with established T1D were recruited before transition from multiple daily injections to insulin-pump therapy from three tertiary pediatric diabetes centers. Participants completed measures of bulimic symptoms, depressive symptoms dietary restraint, and the Diabetes Treatment and Satiety Scale, a diabetes-specific questionnaire assessing hunger and satiety cues and eating behavior in response to blood glucose levels and treatment. Hierarchical multiple regression was used to assess contributions of psychosocial and disease-based risk to report of bulimic symptoms. After assessing the contributions of body mass index, body image dissatisfaction, and dietary restraint, a significant 2-way interaction emerged between depression and diabetes-related uncontrollable hunger related to bulimic symptoms (β = 1.82, p < .01). In addition to psychosocial risk, disease- and treatment-based hunger and satiety dysregulation appear to be important factors contributing to report of bulimic symptoms in youth with T1D. These preliminary findings have significant treatment implications for bulimic symptoms in youth with T1D.


Prospects of Indole derivatives as methyl transfer inhibitors: antimicrobial resistance managers.
It is prudent that novel classes of antibiotics be urgently developed to manage the WHO prioritized multi-drug resistant (MDR) pathogens posing an unprecedented medical crisis. Simultaneously, multiple essential proteins have to be targeted to prevent easy resistance development. An integration of structure-based virtual screening and ligand-based virtual screening was employed to explore the antimicrobial properties of indole derivatives from a compound database. Whole-genome sequences of the target pathogens were aligned exploiting DNA alignment potential of MAUVE to identify putative common lead target proteins. S-adenosyl methionine (SAM) biosynthesizing MetK was taken as the lead target and various literature searches revealed that SAM is a critical metabolite. Furthermore, SAM utilizing CobA involved in the B12 biosynthesis pathway, Dam in the regulation of replication and protein expression, and TrmD in methylation of tRNA were also taken as drug targets. The ligand library of 715 indole derivatives chosen based on kinase inhibition potential of indoles was created from which 102 were pursued based on ADME/T scores. Among these, 5 potential inhibitors of MetK in N. gonorrhoeae were further expanded to molecular docking studies in MetK proteins of all nine pathogens among which 3 derivatives exhibited inhibition potential. These 3 upon docking in other SAM utilizing enzymes, CobA, Dam, and TrmD gave 2 potential compounds with multiple targets. Further, docking with human MetK homolog also showed probable inhibitory effects however SAM requirements can be replenished from external sources since SAM transporters are present in humans. We believe these molecules 3-[(4-hydroxyphenyl)methyl]-6-(1H-indol-3-ylmethyl)piperazine-2,5-dione (ZINC04899565) and 1-[(3S)-3-[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyrrolidin-1-yl]ethanone (ZINC49171024) could be a starting point to help develop broad-spectrum antibiotics against infections caused by N. gonorrhoeae, A. baumannii, C. coli, K. pneumoniae, E. faecium, H. pylori, P. aeruginosa, S. aureus and S. typhi.


Assessment of the Correlation Between Systemic Conditions and Pulp Canal Calcification: A Case-Control Study.
Pulp canal calcification is a dental condition that is characterized by the deposition of mineralized tissue within the dental pulp space. While it is primarily a local phenomenon, recent studies have suggested a potential link between pulp calcification and systemic diseases. This study aimed to determine the correlation between certain systemic diseases, medications, and the presence of pulp canal calcification. Second, it aimed to estimate the prevalence of pulp calcification in the smoker population. A pair-matched case-control observational study was conducted from June 2022 to June 2023 at the Faculty of Dentistry, King Abdulaziz University. Digital periapical and bitewing radiographs were used for case-based sampling. Patients were categorized into two study groups: the cases group (n=100), consisting of patients with pulp canal calcification including either pulp stone, pulp canal obliteration, or both. Whereas the control group (n=100), consisted of patients without pulp canal calcification. Detailed medical histories were obtained to identify the presence of systemic diseases. Additionally, systemic medications and smoking status were documented. The participants were divided into two groups; cases (n=100), diagnosed with teeth calcifications and confirmed by radiographic examination, and controls (n=100), showing no evidence of teeth calcifications. Among the patients in the calcification group, 26% had a history of systemic disease compared to 17% in the control non-calcification group with no significant difference between both groups. No correlation between certain medications and pulp canal calcification. Smoking did not demonstrate a statistically significant association with teeth calcifications (p > 0.05). Pulp calcification on routine radiographic examination could indicate an underlying unnoticed systemic disorder that demands accurate referral and subsequent therapy.


Single amino acid substitution in homogentisate 1,2-dioxygenase is responsible for pigmentation in a subset of Burkholderia cepacia complex isolates.
The Burkholderia cepacia complex (Bcc) is a group of Gram-negative bacilli that are ubiquitous in the environment and have emerged over the past 30 years as opportunistic pathogens in immunocompromised populations, specifically individuals with cystic fibrosis (CF) and chronic granulomatous disease. This complex of at least 18 distinct species is phenotypically and genetically diverse. One phenotype observed in a subset of Burkholderia cenocepacia (a prominent Bcc pathogen) isolates is the ability to produce a melanin-like pigment. Melanins have antioxidant properties and have been shown to act as virulence factors allowing pathogens to resist killing by the host immune system. The melanin-like pigment expressed by B. cenocepacia is produced through tyrosine catabolism, specifically through the autoxidation and polymerization of homogentisate. Burkholderia cenocepacia J2315 is a CF clinical isolate that displays a pigmented phenotype when grown under normal laboratory conditions. We examined the amino acid sequences of critical enzymes in the melanin synthesis pathway in pigmented and non-pigmented Bcc isolates, and found that an amino acid substitution of glycine for arginine at amino acid 378 in homogentisate 1,2-dioxygenase correlated with pigment production; we identify this as one mechanism for expression of pigment in Bcc isolates.


An Improved Tat/Rev Induced Limiting Dilution Assay With Enhanced Sensitivity and Breadth of Detection.
Tat/Rev Induced Limiting Dilution Assay (TILDA) is instrumental in estimating the size of latent reservoirs of HIV-1. Here, we report an optimized TILDA containing a broader detection range compared to the reported methods and high sensitivity. Giving priority to sequence conservation, we positioned the two forward primers and the probe in exon-1 of HIV-1. The reverse primers are positioned in highly conserved regions of exon-7. The optimized TILDA detected eight molecular clones belonging to five major genetic subtypes of HIV-1 with a comparable detection sensitivity. Using the optimized assay, we show that only a minor proportion of CD4+ T cells of primary clinical samples can spontaneously generate multiply spliced viral transcripts. A significantly larger proportion of the cells produced viral transcripts following activation. The optimized TILDA is suitable to characterize HIV-1 latent reservoirs and the therapeutic strategies intended to target the reservoir size.


An immunocytochemical method for demonstrating estrogen receptor in human uterus using monoclonal antibodies to human estrophilin.
We have used monoclonal antiestrophilin antibodies to develop an improved immunocytochemical method for localizing estrogen receptors in tissue sections with an indirect immunoperoxidase technique. Rat monoclonal antibodies were raised against human estrogen receptor (estrophilin) protein derived from the cytosol of MCF-7 human breast cancer cells. These monoclonal antibodies have been shown to have extensive cross-reactivity with estrogen receptors from various primate and nonprimate tissues. We have used frozen sections of human proliferative phase endometrium and an indirect immunoperoxidase technique to establish conditions for demonstrating estrogen receptor antigenic determinants in frozen tissue sections. The method involves (a) brief fixation with formaldehyde-containing fixatives either prior to freezing or immediately after cutting cryostat sections, (b) bleaching the tissue of endogenous peroxidase activity, (c) application of primary antibody or control immunoglobulin, (d) application of an adsorbed bridging antibody (goat antirat IgG), and (e) application of rat peroxidase-antiperoxidase followed by diaminobenzidine. Specific nuclear staining for estrogen receptor antigenic determinants was observed in the vast majority of epithelial and stromal cells. No specific cytoplasmic staining was identified in cryostat sections of any of the 17 cases studied for this report.


MiR-3653 blocks autophagy to inhibit epithelial-mesenchymal transition in breast cancer cells by targeting the autophagy-regulatory genes ATG12 and AMBRA1.
Metastasis is the main cause of tumor-associated death and mainly responsible for treatment failure of breast cancer. Autophagy accelerates tumor metastasis. In our work, we aimed to investigate the possibility of microRNAs (miRNAs) which participate in the regulation of autophagy to inhibit tumor metastasis. MiRNA array and comprehensive analysis were performed to identify miRNAs which participated in the regulation of autophagy to inhibit tumor metastasis. The expression levels of miR-3653 in breast cancer tissues and cells were detected by quantitative real-time polymerase chain reaction. In vivo and in vitro assays were conducted to determine the function of miR-3653. The target genes of miR-3653 were detected by a dual luciferase reporter activity assay and Western blot. The relationship between miR-3653 and epithelial-mesenchymal transition (EMT) was assessed by Western blot. Student's t -test was used to analyze the difference between any two groups, and the difference among multiple groups was analyzed with one-way analysis of variance and a Bonferroni post hoc test. miR-3653 was downregulated in breast cancer cells with high metastatic ability, and high expression of miR-3653 blocked autophagic flux in breast cancer cells. Clinically, low expression of miR-3653 in breast cancer tissues (0.054 ± 0.013 vs . 0.131 ± 0.028, t = 2.475, P = 0.014) was positively correlated with lymph node metastasis (0.015 ± 0.004 vs . 0.078 ± 0.020, t = 2.319, P = 0.023) and poor prognosis ( P < 0.001). miR-3653 ameliorated the malignant phenotypes of breast cancer cells, including proliferation, migration (MDA-MB-231: 0.353 ± 0.013 vs . 1.000 ± 0.038, t = 16.290, P < 0.001; MDA-MB-468: 0.200 ± 0.014 vs . 1.000 ± 0.043, t = 17.530, P < 0.001), invasion (MDA-MB-231: 0.723 ± 0.056 vs . 1.000 ± 0.035, t = 4.223, P = 0.013; MDA-MB-468: 0.222 ± 0.016 vs . 1.000 ± 0.019, t = 31.050, P < 0.001), and colony formation (MDA-MB-231: 0.472 ± 0.022 vs . 1.000 ± 0.022, t = 16.620, P < 0.001; MDA-MB-468: 0.650 ± 0.040 vs . 1.000 ± 0.098, t = 3.297, P = 0.030). The autophagy-associated genes autophagy-related gene 12 ( ATG12 ) and activating molecule in beclin 1-regulated autophagy protein 1 ( AMBRA1 ) are target genes of miR-3653. Further studies showed that miR-3653 inhibited EMT by targeting ATG12 and AMBRA1 . Our findings suggested that miR-3653 inhibits the autophagy process by targeting ATG12 and AMBRA1 , thereby inhibiting EMT, and provided a new idea and target for the metastasis of breast cancer.


An analysis of MyoD-dependent transcription using CRISPR/Cas9 gene targeting in Xenopus tropicalis embryos.
Myogenic regulatory factors (MRFs) are known to have essential roles in both the establishment and differentiation of the skeletal muscle cell lineage. MyoD is expressed early in the Xenopus mesoderm where it is present and active several hours before the activation of muscle differentiation genes. Previous studies in cultured cells and in Xenopus laevis have identified sets of genes that require MyoD prior to differentiation of skeletal muscle. Here we report results from experiments using CRISPR/Cas9 to target the MyoD gene in the diploid frog Xenopus tropicalis, that are analysed by RNA-seq at gastrula stages. We further investigate our data using cluster analysis to compare developmental expression profiles with that of MyoD and α-cardiac actin, reference genes for skeletal muscle determination and differentiation. Our findings provide an assessment of using founder (F0) Xenopus embryos from CRISPR/Cas9 protocols for transcriptomic analyses and we conclude that although targeted F0 embryos are genetically mosaic for MyoD, there is significant disruption in the expression of a specific set of genes. We discuss candidate target genes in context of their role in the sub-programs of MyoD regulated transcription.


Cloning and characterization of a Neurospora crassa gene required for (1,3) beta-glucan synthase activity and cell wall formation.
The glucan synthase 1 gene (gs-1) is required for (1,3) beta-glucan synthase activity [E.C. 188.8.131.52; UDP glucose:1,3-beta-D-glucan 3-beta-D-glucosyltransferase] and for cell wall formation. The gs-1 gene was cloned by functional complementation of the cell-wall-less defect of the (1,3) beta-glucan synthase-deficient mutant, TM1, by using a genomic Neurospora crassa cosmid library. A 2568-nucleotide gs-1 cDNA sequence revealed a 532-amino acid open reading frame encoding a polypeptide of 59 kDa. The predicted gs-1 gene product has no obvious signal peptide cleavage sites or transmembrane domains. A gs-1 null mutant is defective for cell wall formation and (1,3) beta-glucan synthase activity. The predicted GS-1 protein is weakly homologous to a putative Saccharomyces cerevisiae transcriptional regulatory protein.


Antifouling activity of six nontoxic chemicals on spore attachment of Ulva fasciata.
Marine biofouling cause severe damage to all marine technologies. Indiscriminate use of toxic metallic antifouling (AF) chemicals (cuprous oxide and TBT) to control the biofouling in turn greatly affects the flora and fauna of the marine ecosystem. In search of environmentally safe and effective AF agents, six nontoxic AF candidates were studied against the spore attachment of Ulva fasciata. Spore attachment was inhibited at 100 microg of trans-cinnamic acid (TCA) and benzoic acid (BA). Sulfate-coumaric acid (SCA) had no significant effect on the spore attachment. The release rate of BA exhibited a constant release flow. Varied response of U. fasciata spores to AF chemicals and release rate to the surrounding medium are discussed.


Identification of benzenoid and quinonoid structures by through-space NMR shieldings (TSNMRS).
The spatial magnetic properties (through-space NMR shieldings (TSNMRS)) of benzenoid and quinonoid structures (hydroquinone/p-benzoquinone, p-phenylendiamine/p-phenylendiimine, pentacene, and N-containing heteropentacenes) have been calculated by the GIAO perturbation method employing the nucleus-independent chemical shift (NICS) concept of Paul von Rague Schleyer and visualized as isochemical shielding surfaces (ICSS) of various size and direction. The TSNMRS values, thus obtained, can be successfully employed to quantify and visualize the (anti)aromaticity of the compounds studied and to identify readily the existence of benzenoid and quinonoid structures, respectively. As an alternative, computed (as compared with experimental) (1)H chemical shifts can be employed.


Choosing continence products for children.
A wide variety of continence products are available, and the range is changing constantly. Selecting products for children with continence difficulties requires sound knowledge, thorough assessment, regular review, and involvement of the child and family. This article provides some guidance on the products available and how to make an informed choice.


Leaving distal colorectal hyperplastic polyps in place can be achieved with high accuracy by using narrow-band imaging: an observational study.
Accurate colonoscopic assessment of colorectal polyp histology could avoid resection of distal nonadenomatous polyps and reduce costs and risk. To assess the accuracy of predicting histology by using narrow-band imaging (NBI) in real time for distal colorectal polyps. Prospective observational study. University hospital and ambulatory surgery center. This study involved 225 consecutive adults undergoing elective screening or surveillance colonoscopy. We evaluated real-time histology of 235 distal (rectosigmoid) colorectal polyps from 31 patients by using high-definition colonoscopy and NBI without optical magnification. For each polyp, the endoscopist described size, Paris classification, and surface characteristics (vascular and pit pattern, color, pseudodepression). Before resection, histology was predicted, and a level of confidence (high or low) was assigned. Sensitivity and negative predictive value of high-confidence endoscopic predictions of adenomatous versus hyperplastic histology for polyps ≤ 5 mm. The accuracy of a high-confidence endoscopic prediction was 97.7%, sensitivity for adenomatous histology 93.9%, specificity 98.4%, negative predictive value 97.9%, and positive predictive value 75.6%. The performance characteristics for predicting diminutive distal polyps (≤ 5 mm) with high confidence were sensitivity 96.0%, specificity 99.4%, negative predictive value 99.4%, and positive predictive value 96.0%. Single-center study with a single endoscopist. NBI without optical magnification is sufficiently accurate to allow distal hyperplastic polyps to be left in place without resection and small, distal adenomas to be discarded without pathologic assessment. These findings validate NBI criteria based on color, vessels, and pit characteristics for predicting real-time colorectal polyp histology.


Blood haemoglobin concentrations are higher in smokers and heavy alcohol consumers than in non-smokers and abstainers: should we adjust the reference range?
The blood haemoglobin concentration is one of the most frequently used laboratory parameters in clinical practice. There is evidence that haemoglobin levels are influenced by tobacco smoking. The objective of this study was to evaluate the impact of smoking and alcohol consumption on haemoglobin concentrations in apparently healthy subjects living at sea level. A retrospective, epidemiological cohort study was performed in 1984. Participants were 1,503 men and 1,437 non-pregnant women evenly distributed in age cohorts of 30, 40, 50, and 60 years. Information of smoking habits and alcohol consumption were obtained by a questionnaire. Haemoglobin was measured in the fasting state on Coulter-S. Men displayed no difference in mean haemoglobin levels in the four age groups. In women, mean haemoglobin increased gradually with age (p = 0.001). Fifty-nine percent of men and 50% of women were daily smokers. Female smokers displayed a significant positive correlation between number of cigarettes/day and haemoglobin concentrations (r = 0.12, p = 0.002). Heavy smokers (more than ten cigarettes/day) had significantly higher mean haemoglobin (1.4% higher in men, on average 3.5% higher in women) than non-smokers (p < 0.01). Smokers demonstrated a significant correlation between cigarettes/day and drinks/week in men (r = 0.24, p < 0.001) and women (r = 0.16, p < 0.001). Non-smokers displayed a significant positive correlation between drinks/week and haemoglobin concentrations in men (r = 0.14, p = 0.001) and women (r = 0.08, p = 0.05). In non-smokers, alcohol consumption >14 drinks/week and more than seven drinks/week for men and women, respectively, increased mean haemoglobin by 1.3% in men and by average 1.9% in women compared with those consuming < or =14 and less than or equal to seven drinks/week. Smokers displayed similar results. Body mass index per se had no direct influence on haemoglobin levels but had indirect positive influence in men through its correlation with tobacco smoking and alcohol consumption. Tobacco smoking has an increasing effect on haemoglobin concentrations in both genders, which is proportional to the amount of tobacco smoked. The effect appears to be more pronounced in women. Likewise, high alcohol consumption has an increasing effect on haemoglobin in both genders, being most pronounced in women. However, in clinical biochemistry, the relatively small changes in haemoglobin do not justify the use of separate reference ranges in smokers and alcohol consumers.


Propagation Properties of a Surface Plasmonic Waveguide with double elliptical air cores.
We introduce a kind of surface plasmonic waveguide with double elliptical air cores. The dependence of distribution of longitudinal energy flux density, effective index and propagation length of the fundamental mode supported by this waveguide on geometrical parameters and working wavelengths are analyzed using the finite-difference frequency-domain (FDFD) method. Results show that the longitudinal energy flux density distributes mainly in the two wedged corners which are formed by two elliptical air cores, and the closer to the corners the stronger the longitudinal energy flux density. The effective index and propagation length of the fundamental mode can be adjusted by the centric distance of two ellipses as well as the size of the two semiaxis. At the certain working wavelength, relative to the e case of a = b , in the case of a > b , the energy in the metal is small, then the interaction of field and silver is weak, and the effective index becomes small, and the propagation length becomes large. With certain geometric parameters, relative to the case of lambda = 632.8nm , in the case of larger lambda, the area of field distribution is large, and the energy in the metal is small, then the interaction of field and silver is weak, and the effective index becomes small, and the propagation length becomes large. This kind of hollow surface plasmonic waveguide can be applied to the field of photonic device integration and sensors.


Purification, characterization, thermal, and high-pressure inactivation of pectin methylesterase from bananas (cv Cavendish).
Pectin methylesterase (PME) was extracted from bananas (cv Cavendish) and purified by affinity chromatography on a CNBr-Sepharose-PME inhibitor (PMEI) column. A single protein and PME activity peak was obtained. For banana PME, a biochemical characterization in terms of molar mass (MM), pI, and kinetic parameters was performed. In a second step, the thermal and high-pressure stability of the enzyme was studied. Isothermal inactivation of purified banana PME could be described by a first-order kinetic model in a temperature range of 65 degrees to 72.5 degrees C, whereas its isobaric-isothermal inactivation followed a fractional-conversion model. Banana PME was found to be more thermally stable compared with PMEs extracted from orange, tomato, and apple.


Screening for electrically conductive defects in thin functional films using electrochemiluminescence.
Multifunctional thin films in energy-related devices often must be electrically insulating where a single nanoscale defect can result in complete device-scale failure. Locating and characterizing such defects presents a fundamental problem where high-resolution imaging methods are needed to find defects, but imaging with high spatial resolution limits the field of view and thus the measurement throughput. Here, we present a novel high-throughput method for detecting sub-micron defects in insulating thin films by leveraging the electrochemiluminescence (ECL) of luminol. Through a systematic study of reagent concentrations, buffers, voltage, and excitation time, we identify optimized conditions under which it is possible to detect sub-micron defects at high-throughput. Extrapolating from the signal to background observed for detecting 440 nm wide lines and 620 nm diameter circles, we estimate the minimum detectable features to be lines as narrow as 2.5 nm in width and pinholes as small as 70 nm in radius. We further explore this method by using it to characterize a nominally insulating poly(phenylene oxide) film and find conductive defects that are cross-correlated with high-resolution atomic force microscopy to provide feedback to synthesis. Given this assay's inherent parallelizability and scalability, it is expected to have a major impact on the automated discovery of multifunctional films.


Drug-induced liver injury associated with Stevens-Johnson syndrome/toxic epidermal necrolysis: Patient characteristics, causes, and outcome in 36 cases.
The liver and skin are the organs most commonly involved in serious adverse drug reactions. Rarely a drug reaction can affect both organs concurrently. The association of drug-induced liver injury (DILI) and Stevens-Johnson syndrome (SJS) or toxic epidermal necrosis (TEN) is even rarer and not well studied. We describe our experience of DILI occurring in association with SJS/TEN including the etiologic agents, clinical and biochemical characteristics, and outcome. We identified patients who developed DILI in association with SJS/TEN from a registry of DILI patients from a single center. Causality assessment for DILI and SJS/TEN was carried out with the Roussel Uclaf Causality Assessment Method and the Algorithm for Drug Causality for Epidermal Necrolysis, respectively. Among 748 consecutive patients with DILI from 1997 to March 2015, 36 (4.8%) had associated features of SJS/TEN. The mean age was 32 years (females 19). Children and patients with human immunodeficiency virus constituted 25% (n = 9) and 22% (n = 8), respectively. Only a small number of "high-risk" drugs such as antiepileptic agents, sulfonamides, and antiretroviral drugs accounted for the majority of cases. Overall mortality was 36% (n = 13), which rose to 45.5% in the presence of jaundice. Mortality was less in children 11% (n = 1) and human immunodeficiency virus patients 12.5% (n = 1). DILI associated with SJS/TEN is rare and associated with a high death rate, particularly in those with jaundice; however, children and human immunodeficiency virus-infected individuals have a favorable outcome; a small group of drugs contributed to a disproportionate number of cases, and causality with Roussel Uclaf Causality Assessment Method and the Algorithm for Drug Causality for Epidermal Necrolysis was highly probable or probable in all cases.


Assessment of quality of life in veterinary practice: developing tools for companion animal carers and veterinarians.
Quality-of-life assessments aim to provide an all-encompassing evaluation of animal welfare. In comparison to more limited, disease-focused welfare assessments, they have the potential to better identify welfare deficiencies, allowing veterinarians to target improvement strategies for greater benefit. Individuals or populations of companion animals may be assessed and carers and/or veterinarians may contribute to the assessment. Quality-of-life assessments are widely used within the human health care setting, and although the number of veterinary assessment tools is substantially fewer, these tools cover a range of methodologies. Further research to validate existing tools and develop new ones is recommended. Guidance for implementing and evaluating the usefulness of quality-of-life assessment tools within companion animal veterinary clinics is presented.


The role of drugs and selected dietary factors in cutaneous squamous cell carcinogenesis.
Cutaneous squamous cell carcinoma represents the second most common non-melanoma skin cancer and its incidence increases worldwide. This review provides an overview of selected exogenous risk factors for cutaneous squamous cell carcinoma, which include drugs (azathioprine, calcineurin inhibitors, hydrochlorothiazide, angiotensin-converting-enzyme inhibitors) and few dietary factors (fat meet, whole milk products, arsenic) to better understand squamous skin cancer etiopathogenesis. Ingredients such as leafy vegetables, nuts, fish, caffeine, niacin are preventive factors for cutaneous squamous cell cancer. The heart transplant recipients have an increased risk of squamous cell carcinoma development than kidney or liver transplant ones and switching photosensitizing azathioprine to mycophenolate mofetil can reduce the incidence of cutaneous squamous cell carcinoma. The great attention should be paid to early change of cardiac photosensitizing antihypertensive drugs to non-photosensitizing ones among patients with a history of prior skin cancers and among organ transplant recipients. Based on current knowledge that ultra-violet radiation is the main risk factor for squamous cell carcinoma development, promotion of the skin self-examination, photoprotection, tanning bed avoidance and early skin cancer diagnosis is important for this tumour prevention.


Analysis of inflammatory cells and mediators in skin wound biopsies to determine wound age in living subjects in forensic medicine.
In forensic medicine it is important to determine the age of skin wounds in living subjects. The aim of this study was to assess whether analysis of inflammatory cells and inflammatory mediators in skin biopsies of wounds from living subjects could improve wound age determination. Biopsies (n=101), representing the superficial border area of a skin wound, were taken from skin injuries of known wound age (range: 4.5 hours to 25 days) of living subjects. All biopsies were analyzed for 3 inflammatory cell markers (MPO, CD45 and CD68) and 4 inflammatory mediators (MIP-1, IL-8, CML and vitronectin). For quantification, biopsies were subdivided in 4 different timeframes: 0.2-2 days, 2-4 days, 4-10 days and 10-25 days old wounds. Subsequently, a probability scoring system was developed. MPO, CD45, MIP-1, IL-8 (inflammatory cell markers) and N(epsilon)-(carboxymethyl)lysine (CML) positivity were maximal in wounds of 0.2-2 days old and then decreased in time. Remarkably, CD45, CD68 and CML showed a minor but non-significant increase again in 10-25 days old wounds. MPO and CD68 positivity was significantly lower in 4-25 days old wounds compared to 0.2-4 days old wounds. MPO positivity was also significantly lower in 10-25 days old wounds compared to 0.2-10 days old wounds. For CD45, MIP-1, IL-8 and CML no significant differences between the age groups were found. In case of vitronectin positivity in the extravasate or when the number of MIP-1 or IL-8-positive cells was more than 10 cells/mm(2) the probability that a wound was more than 10 days old was 0%. A probability scoring system of all analyzed markers can be used to calculate individual wound age probabilities in biopsies of skin wounds of living subjects. We have developed a probability scoring system of inflammatory cells and mediators that can be used to determine wound age in skin biopsies of living subjects.


Uterine rupture at 26 weeks of pregnancy following laparoscopic salpingectomy with resection of the interstitial portion: a case report.
Uterine rupture in pregnancy can occur in patients with a history of uterine surgery such as myomectomy and Cesarean section. Here, we report a case of spontaneous uterine rupture that occurred in the early third trimester in a pregnant woman who had previously undergone laparoscopic removal of the right fallopian tube and interstitial portion for treatment of interstitial pregnancy. The patient presented with sudden onset of abdominal pain at 26 weeks of gestation. Detailed ultrasonography and magnetic resonance imaging led to diagnosis of uterine rupture. In emergency laparotomy, the fetus was delivered by Cesarean section, the placenta and membranes were removed, and the uterus was preserved with closure of the rupture and wound. This case highlights the importance of close follow-up of a pregnant patient who has previously had a uterine incision. The case also raises the question of whether the prevalence of uterine rupture may increase as more patients are treated with laparoscopic surgery of the uterus.


Abiotrophia Defectiva as a Rare Cause of Mitral Valve Infective Endocarditis With Mesenteric Arterial Branch Pseudoaneurysm, Splenic Infarction, and Renal Infarction: A Case Report.
Abiotrophia defectiva (A. defectiva) is a rare species leading to infective endocarditis (IE) with a poor prognosis. We describe a previously healthy patient with mitral valve infective endocarditis caused by A. defectiva. A young man was admitted with intermittent fever. Echocardiography confirmed vegetation on the mitral valve with evidence of valve perforation and severe mitral regurgitation. Three sets of blood cultures became positive for A. defectiva. As he presented with manifestations of mesenteric arterial branch pseudoaneurysm, splenic and renal infarction, mitral valve replacement, and embolization of superior mesenteric aneurysm were operated during 8 weeks' targeted antibiotic therapy. This case study emphasizes the importance of considering A. defectiva as a rare but important cause of IE and of performing blood culture to make its accurate diagnosis and timely anti-infective treatment. Early surgical management and active prevention of complications have been associated with a favorable prognosis.


Radiological/pathological correlations in uremic bone disease.
Skeletal radiographs and non-decalcified bone specimens from 17 chronically uremic patients with radiographic evidence of bone disease were studied quantitatively. The results of each morphological technique were compared in an attempt to define the roentgenographic manifestations of renal osteodystrophy histologically. The radiographs correlated best with the trabecular bone manifestations of osteitis fibrosa but showed poor correlation with histological evidence of osteomalacia. Radiographic signs of osteosclerosis could not be correlated with any radiographic or histiolgical feature of bone resorption.


Homeless veterans' experiences with substance use, recovery, and treatment through photo elicitation.
Homeless veterans often have addictions and comorbidities that complicate utilization of longitudinal health care services, such as primary care. An understanding of experiences of veterans enrolled in a Homeless Patient Aligned Care Team (H-PACT) may improve addiction treatment engagement in these settings. The authors aimed to describe H-PACT veterans' experiences with substance use (SU), substance use recovery (SUR), and substance use treatment (SUT). Homeless veterans were recruited from a veteran primary care medical home clinic between September 2014 and March 2015. Twenty veterans were given digital cameras and prompts for taking photographs about their health and health care and participated in 2 photo elicitation interviews. For this secondary analysis, transcripts from the audio-recorded interviews were analyzed by 2 coders using qualitative content analysis. The majority of participants (75%, n = 15) discussed SU, SUR, and/or SUT in regards to their health and health care utilization. SU themes centered on disclosure of addiction or dependency; substances used; repercussions of SU; SU as a coping mechanism; and association of SU with military service. SUR themes included disclosure of length of sobriety; perceived facilitators of SUR in health, beliefs, social, environmental, financial, and creative pursuit domains; and perceived barriers to SUR in beliefs, social, and environmental domains. SUT themes focused on perceived facilitators of SUT in access to Department of Veterans Affairs (VA) and non-VA services and social domains and perceived barriers to SUT in the social domain. Providers seeking to elicit addiction-related clinical history and facilitate SUR and SUT might look to the current findings for guidance. Provider training in motivational interviewing may be warranted, which allows for an exploration of health-related consequences of SU and supports patients' self-efficacy.


Twin Peaks? No Evidence of Bimodal Distribution of Outcomes in Clinical Trials of Nonsurgical Interventions for Spinal Pain: An Exploratory Analysis.
The presence of bimodal outcome distributions has been used as a justification for conducting responder analyses, in addition to, or in place of analyses of the mean between-group difference, in clinical trials and systematic reviews of interventions for pain. The aim of this study was to investigate the distribution of participants' pain outcomes for evidence of bimodal distribution. We sourced data on participant outcomes from a convenience sample of 10 trials of nonsurgical interventions (exercise, manual therapy, medication) for spinal pain. We assessed normality using the Shapiro-Wilk test. When the Shapiro-Wilk test suggested non-normality we inspected distribution plots visually and attempted to classify them. To test whether responder analyses detected a meaningful number of additional patients experiencing substantial improvements we also calculated the risk difference and number needed to treat to benefit. We found no compelling evidence suggesting that outcomes were bimodally distributed for any of the intervention groups. Responder analysis would not meaningfully alter our interpretation of these data compared with the mean between group difference. Our findings suggest that bimodal distribution of outcomes should not be assumed in interventions for spinal pain and do not support the automatic prioritization of responder analysis over the between group difference in the evaluation of treatment effectiveness for pain. Secondary analysis of clinical trials of nonsurgical interventions for spinal pain found no evidence for bimodally distributed outcomes. The findings do not support the automatic prioritization of responder analyses over the average between group difference in the evaluation of treatment effectiveness for spinal pain.


Hemospermia after transrectal ultrasound (TRUS)-guided prostatic biopsy: a prospective study.
Trans-rectal Ultrasound (TRUS) is a safe, cost-effective, radiation free imaging modality for evaluation of prostate. But unfortunately, hemospermia is known to be associated with TRUS -guided prostate biopsy. This study measured the incidence & risk factors, of hemospermia in patients undergoing trans-rectal ultrasonography (TRUS). A prospective observational study involving patients undergoing TRUS for suspected prostate cancer has been conducted at Al-Hussein and Sayed Galal, University Hospitals. 40patients were included in the study. The results showed that 18 out of 40 patients (45%) undergoing TRUS-guided prostatic biopsy, who were able to ejaculate, experienced hemospermia, which was associated with some degree of anxiety. The mean duration of hemospermia was 4 (+/- 1.4) weeks. The number of ejaculations before the complete resolution of hemospermia was 6 (+/- 5.6). None of the clinical and pathological factors were significant predictors of the duration of hemospermia.


Partnering with family members to improve the intensive care unit experience.
Family members play an important and varied role in a patient's health care experience, ranging from emotional support to surrogate health care decision making. The family role can be substantial in the intensive care unit setting, as the patients rely upon family members to make health care decisions for them. The core components of patient- and family-centered care include information sharing, a welcoming environment, respect for individual values and needs, comfort and support, and providing a helpful framework for developing a productive partnership with family members. Involving family members in daily operations and providing services that make it easier for family members to participate in the care process result in the best possible care for their loved one. Including the family perspective in quality improvement initiatives better ensures that any changes made will result in better care for future patients and family members.


[Demonstration and classification of heterogeneity of phosphoprotein phosphohydrolase in swine spleen extracts based on sodium fluoride inhibition].
The heterogeneity of phosphoprotein phosphohydrolase--Fpf in cellular free spleen extracts of pigs may be determined by sodium fluoride inhibition. NaF concentration of 5 X 10(-3) mol/l divides Fpf into 3 groups and shows a wide inhibition range from 15 to 85% of the initial activity of the enzyme. Naf concentration of 5 X 10(-4)mol/l stops Fpf activity in the range from 10 to 65% and divides it into two groups. To classify the studied material into Fpf phenotypes, fluoride quotient index--WIF has been proposed which expresses the relationship between the percentage of the inhibition caused by NaF at a concentration 5 X 10(-3) mol/l and that of the inhibition caused by NaF at a concentration of 5 X 10(-4) mol/l in the reaction mixture and in the measurement conditions described in the methods. Five groups with the following numerical values of WIF have been distinguished: 1.15 less than or equal to WIF less than 1.40-44%--group I; 1.50 less than or equal to WIF less than 1.80-20%--group II; 1.90 less than or equal to WIF less than 2.10-16%--group III; 2.20 less than or equal to WIF less than 2.50-16%--group IV; and WIF = 3-4%--group V.


Management of a Patient With Tetralogy of Fallot, Congenital Diaphragmatic Hernia, and Complete Left Lung Agenesis.
We describe the rare case of an infant with congenital diaphragmatic hernia, unilateral lung agenesis, and unpalliated single-ventricle physiology. Infants with congenital diaphragmatic hernia and parallel circulation are at risk for maldistribution of systemic and pulmonary blood flow. Optimal perioperative management should include an assessment of the ratio of pulmonary to systemic blood flow (Qp:Qs). Traditionally, arterial and systemic venous oxygen (SvO2) saturations are needed to calculate Qp:Qs. However, in this case, SvO2 measurement was not feasible. On the basis of a previously described relationship, we used 2-site near-infrared spectroscopy to calculate a near-infrared spectroscopy-derived SvO2, which was then used to estimate Qp:Qs and guide goal-directed interventions.


Genetic association between a single nucleotide polymorphism in Interleukin-16 (rs4072111) and susceptibility to chronic HCV infection in an Iranian population.
Our goal was to identify the putative association of rs4072111 variant in IL-16 gene and HCV susceptibility in an Iranian population. Interleukin 16 (IL-16), a multifunctional cytokine, plays a vital role in modulation of immune system. In present case control and cross sectional study, IL-16 gene variant in 300 patients with hepatitis C (HCV) infection and 300 healthy individuals were analyzed. To evaluate this possible association, genomic DNA from venous blood was extracted and genotypes of IL-16 rs4072111 variant were determined by polymerase chain reaction- Fragments Length Polymorphism Technique (PCR-RFLP). Then, rs4072111 C/T genotypes frequency and allelic distribution were evaluated in each group. The results of genotyping showed 82% CC, 17.3% CT, 0.7% TT in the control group and 78% CC, 20% CT and 2% TT in the case group. The distribution of rs4072111 C allele was 90.7% in controls and 88% in case group respectively.However, no correlation between IL-16 rs4072111 C/T variants and susceptibility to chronic HCV infection was found in the present study. We concluded the rs4072111 C/T cannot be considered as a proper biomarker to identify susceptibility to chronic hepatitis C virus infection.


[Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic change induced by transforming growth factor-beta1].
To illuminate the possible role of Prohibitin (PHB) in tubulointerstitial fibrosis. (1) Forty-eight renal biopsy specimens were obtained from the patients with various primary glomerulonephritis, 26 male and 22 female, aged 7.5 +/- 5.5 (2.5 - 13 years), and nine kidney tissue specimens were obtained form the tissues far away from the tumor tissues and confirmed by pathological examination as normal tissues in the kidney dissected during operation as normal control. Immunohistochemistry was used to detect the protein expression of PHB and alpha-smooth muscle actin (alpha-SMA). The correlation between PHB and degree of tubulointerstitial lesion was compared. (2) Rat kidney fibroblastoma cells of the line NRK-49F were cultured, and laser scanning confocal microscopy was used to observe the subcellular location of PHB protein. The changes of PHB protein and mRNA expression in the NRK-49F cells upon TGF-beta1 stimulation were detected by Western blotting and RT-PCR analysis. (3) PHB expression plasmid was constructed and transfected into the NRK-49F cells. Then, cell cycle analysis was performed by flow cytometry, and Western blotting and RT-PCR were performed to detect the PHB and alpha-SMA protein and mRNA expression in the NRK-49F cells treated with or without TGF-beta1. (1) PHB protein expression was found in the normal renal tissues by immunohistochemistry, with a positive distribution in the interstitial cells and tubular epithelial cells. PHB was strongly down-regulated in the damaged interstitial and tubular epithelial cells, the higher the grade of damage, the lower the expression of PHB (all P < 0.01), and the PHB expression amount was negatively correlated with the degree of tubulointerstitial lesions (r = -0.802, P < 0.01). (2) Confocal microscopy showed that PHB was mainly located in the cytoplasm and weakly expressed in the nucleus of the NRK-49F cells. Treated with TGF-beta1, the PHB protein expression and mRNA expression in the NRK-49F cells were decreased both time-dependently and dose-dependently (all P < 0.01). (3) A recombinant pcDNA3.1 (-)/PHB plasmid was successfully constructed. PHB protein expression in the transfected NRK-49F cells was 2.54 times higher compared with the non-transfected cells. (4) The proportions of the cells in the S and G(2)/M phases were higher in the NRK-49F cells stimulated by TGF-beta1, however, more NRK-49F cells remained in the G(0)/G(1) phase after transfection of PHB (P < 0.01). (5) Both alpha-SMA protein and mRNA were not expressed in the control cells while de novo expression of alpha-SMA in the NRK-49F cells was increased after the treatment of TGF-beta1. Over-expression of PHB did not affect he basic alpha-SMA expression but dramatically repressed TGF-beta1-initiated alpha-SMA expression in the NRK-49F cells (P < 0.01). PHB protein is expressed in the normal renal tissues and adversely correlated with the degree of tubulointerstitial lesions. Extraneous PHB suppresses renal interstitial fibroblast proliferation and cell phenotypic change induced by TGF-beta1.


Tympanic membrane cholesteatoma (keratoma).
Four cases of tympanic membrane cholesteatoma are presented and the characteristics of this lesion are discussed. Failure to recognize and remove all the squamous epithelium medial to the tympanic membrane at the time of grafting eventually will result in graft breakdown due to continued production and desquamation of squamous epithelium into the middle ear.


Resource Partitioning between Two Piranhas (Serrasalmus gibbus and Serrasalmus rhombeus) in an Amazonian Reservoir.
The exploitation of resources by closely related species with similar niches may be mediated by differences in activity patterns, which may vary in nycthemeral scale and seasonal scale. Piranhas Serrasalmus gibbus and Serrasalmus rhombeus are Neotropical predators that occur sympatrically in many environments of the Amazon basin. To evaluate the strategies adopted by these two species in a restricted environment (a reservoir), nycthemeral and seasonal samples were made, identifying the composition of the diet and their activity patterns. A total of 402 specimens were collected: 341 S. gibbus and 61 S. rhombeus. Both species fed themselves primarily on fish, with some seasonal variation being found in S. gibbus during the flood season, when plant material was consumed. There was considerable temporal overlap in the foraging behavior of the two species, although S. rhombeus presented a bimodal pattern of abundance over the 24-hour cycle. S. rhombeus was more active during the nighttime, between dusk and early morning, whereas S. gibbus was active throughout the nycthemeral cycle. These findings indicate low levels of competition between the two species, which allowed for a considerable overlap in nighttime foraging, following distinct nycthemeral patterns of foraging activity and allowing their coexistence.


Doppler ultrasonography can be used to evaluate the arterial blood supply of hip joints in skeletally immature cats.
To investigate hemodynamics and morphology of hip joint vasculature in cats with the use of color and pulsed-wave Doppler ultrasonography. 30 client-owned healthy skeletally immature cats presented for routine examinations between September 7, 2022, and March 25, 2023. Cats between 3.5 to 18 months old with healthy hip joints and Hct within reference ranges (26% to 44.2%) were eligible for inclusion. Color and pulsed-wave Doppler ultrasonography was performed without sedation. Peak systolic velocity (PSV), mean diastolic velocity (MDV), resistance index (RI), and pulsatility index (PI) were measured for major arteries of the hip joints. Intermediate pulsatility, resistance to flow, and pandiastolic anterograde flow were evident for all arteries evaluated for each joint except for the ligamentum capitis ossis femoris artery (LCOFA). Spectral waveforms for the LCOFA showed a low-resistance pattern with continuous forward diastolic flow. No significant differences were found in the mean PI or MDV between the left and right sides for the ascending branch of the lateral circumflex femoral artery or in the mean PI of the ascending branch of the medial circumflex femoral artery. Mean PSV of the LCOFA was lower (but nonsignificantly) for left hip joints vs right hip joints, whereas other values were often higher on cats' left side vs their right. This study provided insight into the morphology and hemodynamics of the femoral head vasculature in skeletally immature cats and showed Doppler ultrasound values to study the clinically normal blood supply to hip joints in cats.


It is All in the Wrist: Wearable Sleep Staging in a Clinical Population versus Reference Polysomnography.
There is great interest in unobtrusive long-term sleep measurements using wearable devices based on reflective photoplethysmography (PPG). Unfortunately, consumer devices are not validated in patient populations and therefore not suitable for clinical use. Several sleep staging algorithms have been developed and validated based on ECG-signals. However, translation from these techniques to data derived by wearable PPG is not trivial, and requires the differences between sensing modalities to be integrated in the algorithm, or having the model trained directly with data obtained with the target sensor. Either way, validation of PPG-based sleep staging algorithms requires a large dataset containing both gold standard measurements and PPG-sensor in the applicable clinical population. Here, we take these important steps towards unobtrusive, long-term sleep monitoring. We developed and trained an algorithm based on wrist-worn PPG and accelerometry. The method was validated against reference polysomnography in an independent clinical population comprising 244 adults and 48 children (age: 3 to 82 years) with a wide variety of sleep disorders. The classifier achieved substantial agreement on four-class sleep staging with an average Cohen's kappa of 0.62 and accuracy of 76.4%. For children/adolescents, it achieved even higher agreement with an average kappa of 0.66 and accuracy of 77.9%. Performance was significantly higher in non-REM parasomnias (kappa = 0.69, accuracy = 80.1%) and significantly lower in REM parasomnias (kappa = 0.55, accuracy = 72.3%). A weak correlation was found between age and kappa (ρ = -0.30, p<0.001) and age and accuracy (ρ = -0.22, p<0.001). This study shows the feasibility of automatic wearable sleep staging in patients with a broad variety of sleep disorders and a wide age range. Results demonstrate the potential for ambulatory long-term monitoring of clinical populations, which may improve diagnosis, estimation of severity and follow up in both sleep medicine and research.


Psychobiologic research in post-traumatic stress disorder.
PTSD can be a chronic, devastating disorder for which treatment is only partially effective. For some, this disorder progressively worsens over time and appears to affect nearly every aspect of life, including work, interpersonal relationships, physical health, and view of self. Although generally understood as a psychological disorder, PTSD also may be viewed from a biologic perspective. There is now accumulating evidence to suggest that severe psychological trauma can cause alterations in the organism's neurobiologic response to stress even years after the original insult. Long-standing alterations in the biologic response to stress may contribute to a number of complaints commonly expressed by patients with PTSD. For example, increased sensitivity and sensitization of the noradrenergic system may leave the individual in a hyperaroused, vigilant, sleep-deprived, and, at times, explosive state that worsens over time. Being irritable and on edge makes it difficult to interact with family members, friends, coworkers, and employers. To quiet these symptoms of hyperarousal, PTSD patients often withdraw and use substances, particularly central nervous system depressants, that suppress peripheral and central catecholamine function. Alterations in other neurobiologic systems may further contribute to multiple symptoms, such as intrusive memories, dissociation phenomena, and even numbing. Characterization of the biologic underpinnings of PTSD relies to a large degree on available neurobiologic technology. Much of what has been discussed in this article has grown out of advances in physiologic, hormone, and receptor assay methodology. With further advances in neurobiologic technology, in areas such as brain imaging, it soon will be possible to better delineate acute and long-term stress-induced changes in central and peripheral nervous system functioning. Undoubtedly a far richer, more complex understanding of neurobiologic responses and alterations will emerge in the near future. It is believed that an improved neurobiologic understanding will facilitate the development of more specific, effective treatments for individuals who have been severely traumatized.


[A basic study on plasma exchange therapy of malignant tumor in tumor bearing rats].
We conducted an experimental animal study to make a comparative evaluation of therapeutic effects of plasma exchange alone and combination therapy. The subjects of this study were divided into four groups: (1) untreated group (control). (2) plasma exchange group (PE). (3) Mitomycin C treated group (MMC: active control) and (4) plasma exchange + MMC treated group (combination therapy). A tumor inhibiting effect was observed in the MMC and combination therapy groups, but was absent in the PE group. The survival-periods, however, were extended in the PE group, and to a significant extent in the combination therapy group. Alpha 1 acid glycoprotein (alpha 1 AGP) whose plasma level is low in the normal, is demonstrated to increase linealy with the tumor load in the plasma of cancer-bearing rats. And it is observed to decreased after plasma exchange. Present basic studies suggested that plasma exchange alone has a survival-prolonging effect, but produces no inhibitory effect on tumor growth, and the combination therapy has a greater life-extending effect than plasma exchange alone or chemotherapy alone.


Asymmetrical hypersensitivity to bovine collagen.
We report a unique patient with true asymmetrical hypersensitivity to bovine collagen. Hypersensitivity is the development of an inflammatory response at a treatment site after a negative skin test. She developed an inflammatory response in only one of two simultaneously injected sites. About 1.5% of patients with a negative skin test have a hypersensitivity reaction consisting of firmness, erythema, and swelling. The signs and symptoms generally resolve spontaneously in a few months.


Trans-splicing enhances translational efficiency in C. elegans.
Translational efficiency is subject to extensive regulation. However, the factors influencing such regulation are poorly understood. In Caenorhabditis elegans, 62% of genes are trans-spliced to a specific spliced leader (SL1), which replaces part of the native 5' untranslated region (5' UTR). Given the pivotal role the 5' UTR plays in the regulation of translational efficiency, we hypothesized that SL1 trans-splicing functions to regulate translational efficiency. With genome-wide analysis on Ribo-seq data, polysome profiling experiments, and CRISPR-Cas9-based genetic manipulation of trans-splicing sites, we found four lines of evidence in support of this hypothesis. First, SL1 trans-spliced genes have higher translational efficiencies than non-trans-spliced genes. Second, SL1 trans-spliced genes have higher translational efficiencies than non-trans-spliced orthologous genes in other nematode species. Third, an SL1 trans-spliced isoform has higher translational efficiency than the non-trans-spliced isoform of the same gene. Fourth, deletion of trans-splicing sites of endogenous genes leads to reduced translational efficiency. Importantly, we demonstrated that SL1 trans-splicing plays a key role in enhancing translational efficiencies of essential genes. We further discovered that SL1 trans-splicing likely enhances translational efficiency by shortening the native 5' UTRs, hence reducing the presence of upstream start codons (uAUG) and weakening mRNA secondary structures. Taken together, our study elucidates the global function of trans-splicing in enhancing translational efficiency in nematodes, paving the way for further understanding the genomic mechanisms of translational regulation.


A questionnaire survey of senior house officers/registrars response to their training at University College Hospital, Ibadan.
This study evaluated the responses of randomly selected 54 senior house officers (SHO)/registrars to questions on their training at the University College Hospital, Ibadan, Nigeria. Previous studies have identified excess workload, poor supervision and inadequate hours of formal educations as areas deserving increased attention. The aim of this study is to assess the residents perception of their training and to offer recommendations where necessary. Many residents felt they are often called to attend to problems beyond their experiences and competence. As many as 66.7% as at 3 months and above into training, have not had the opportunity to discuss their training progress with their supervising consultants. The study therefore calls for more hours of formal teaching and consultants' regular evaluation of residents training. A regular conduct of auditing of training programmes is recommended.


ABC transporters and the hallmarks of cancer: roles in cancer aggressiveness beyond multidrug resistance.
The ATP-binding cassette transporters (ABC transporters) have been intensely studied over the past 50 years for their involvement in the multidrug resistance (MDR) phenotype, especially in cancer. They are frequently overexpressed in both naive and post-treatment tumors, and hinder effective chemotherapy by reducing drug accumulation in cancer cells. In the last decade however, several studies have established that ABC transporters have additional, fundamental roles in tumor biology; there is strong evidence that these proteins are involved in transporting tumor-enhancing molecules and/or in protein-protein interactions that impact cancer aggressiveness, progression, and patient prognosis. This review highlights these studies in relation to some well-described cancer hallmarks, in an effort to re-emphasize the need for further investigation into the physiological functions of ABC transporters that are critical for tumor development. Unraveling these new roles offers an opportunity to define new strategies and targets for therapy, which would include endogenous substrates or signaling pathways that regulate these proteins.


Characteristics and Predictors of Long-Time Survivors in Non-Metastatic Gastric Signet Ring Cell Carcinoma: A Large Population-Based Study.
Gastric signet ring cell carcinoma (SRCC) is a distinct entity with a relatively poor prognosis. This study analyzed the clinicopathological characteristics of long-time survivors (LTSs) and identified independent predictors of long-term survival (LTS) in non-metastatic gastric SRCC. Data from 3906 patients with non-metastatic gastric SRCC were retrieved from Surveillance, Epidemiology and End Results according to the inclusion and exclusion criteria. Patients were randomly divided into training and validation cohorts. Predictors of LTS in the training cohort were identified by multivariate logistic regression. A nomogram-based predictive model for LTS was constructed in non-metastatic gastric SRCC. There were 800 patients who survived for >5 years and were defined as TLSs. Young age, other race (not black or white population), female gender, married status, small tumor size, low tumor infiltration, and negative lymph node involvement were independent predictors of LTS in non-metastatic gastric SRCC. These seven variables were incorporated into a nomogram model for predicting LTS. The calibration curve showed good consistency between observed and predicted probability of LTS, and the receiver operating characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. This study provides an overview of the features of patients with non-metastatic gastric SRCC. Age, race, sex, marital status, tumor size, tumor infiltration, and lymph node involvement were identified as independent predictors of LTS.


Influence of ferrous ions on extracellular polymeric substances content and sludge dewaterability during bioleaching.
Pretreatment of activated sludge with sulfuric acid and bioleaching using Acidithiobacillus ferrooxidans along with addition of Fe(2+) on sludge dewaterability was investigated. The sludge dewatering efficiency in terms of capillary suction time (CST) and specific resistant to filtration (SRF) was increased with a decrease in sludge pH. A pH of 2.67 was found to be optimum for dewatering, at which 81% and 63% reduction of CST and SRF were achieved, respectively. The dewaterability of sludge was enhanced after the addition of Fe(2+) and A. ferrooxidans. Ideal concentration of Fe(2+) was 2 g/L for sludge dewaterability, which showed 96% and 88% reduction in CST and SRF, respectively. In the control sludge, maximum part of the biopolymeric macromolecules was contributing by the tightly bound extracellular polymeric substances (TB-EPS). At optimum Fe(2+) concentration, total EPS was reduced by 73%, enhancing sludge dewaterability. Bioleaching conducted by A. ferrooxidans could solubilized 88% Cu and 99% Zn within 120 h.


Long-term concentration of tropical forest nutrient hotspots is generated by a central-place apex predator.
Apex predators typically affect the distribution of key soil and vegetation nutrients through the heterogeneous deposition of prey carcasses and excreta, leading to a nutrient concentration in a hotspot. The exact role of central-place foragers, such as tropical raptors, in nutrient deposition and cycling, is not yet known. We investigated whether harpy eagles (Harpia harpyja) in Amazonian Forests-a typically low soil fertility ecosystem-affect soil nutrient profiles and the phytochemistry around their nest-trees through cumulative deposition of prey carcasses and excreta. Nest-trees occurred at densities of 1.5-5.0/100 km2, and each nest received ~ 102.3 kg of undressed carcasses each year. Effects of nests were surprisingly negative over local soil nutrient profiles, with soils underneath nest-trees showing reductions in nutrients compared with controls. Conversely, canopy tree leaves around nests showed significant 99%, 154% and 50% increases in nitrogen, phosphorus and potassium, respectively. Harpy eagles have experienced a 41% decline in their range, and many raptor species are becoming locally extirpated. These are general examples of disruption in biogeochemical cycles and nutrient heterogeneity caused by population declines in a central-place apex predator. This form of carrion deposition is by no means an exception since several large raptors have similar habits.


Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond.
Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.


Tracking medical genetic literature through machine learning.
There has been remarkable progress in identifying the causes of genetic conditions as well as understanding how changes in specific genes cause disease. Though difficult (and often superficial) to parse, an interesting tension involves emphasis on basic research aimed to dissect normal and abnormal biology versus more clearly clinical and therapeutic investigations. To examine one facet of this question and to better understand progress in Mendelian-related research, we developed an algorithm that classifies medical literature into three categories (Basic, Clinical, and Management) and conducted a retrospective analysis. We built a supervised machine learning classification model using the Azure Machine Learning (ML) Platform and analyzed the literature (1970-2014) from NCBI's Entrez Gene2Pubmed Database (http://www.ncbi.nlm.nih.gov/gene) using genes from the NHGRI's Clinical Genomics Database (http://research.nhgri.nih.gov/CGD/). We applied our model to 376,738 articles: 288,639 (76.6%) were classified as Basic, 54,178 (14.4%) as Clinical, and 24,569 (6.5%) as Management. The average classification accuracy was 92.2%. The rate of Clinical publication was significantly higher than Basic or Management. The rate of publication of article types differed significantly when divided into key eras: Human Genome Project (HGP) planning phase (1984-1990); HGP launch (1990) to publication (2001); following HGP completion to the "Next Generation" advent (2009); the era following 2009. In conclusion, in addition to the findings regarding the pace and focus of genetic progress, our algorithm produced a database that can be used in a variety of contexts including automating the identification of management-related literature.


Documentation of a new contrast medium for the subarachnoid space. Demands, design and results from the first multicentre trial with iohexol.
The first clinical trial with the non-ionic contrast medium iohexol (Omnipaque) in lumbar myelography was performed as a multicentre investigation of a total of 88 included patients. The design of the comprehensive clinical trial program is presented and the necessity of using such an extensive clinical trial program in the early stage of the investigation is discussed. This comprehensive monitoring did not reveal any serious or persistent side effects. The documentation on the safety of the drug encourages further clinical trials.


The Pregnancy Depression Scale (PDS): a screening tool for depression in pregnancy.
Depression in pregnancy can be underdiagnosed as a consequence of the symptoms being misattributed to "normal pregnancy." There are currently no validated clinician-rated scales that assess for depression specifically during pregnancy. We sought to develop a brief, convenient screening tool to identify depression in pregnant women in the community setting. Prospective mood data using the 28-item Hamilton Depression Rating Scale (HDRS) were collected monthly in 196 pregnant women with a history of a major depressive disorder. These data were analyzed to delineate those HDRS items associated (elevated) with normal pregnancy vs. those indicative of a pregnant woman meeting diagnostic criteria for a major depressive episode. Endorsement of symptoms on seven items of the HDRS were highly predictive of having a major depressive episode during pregnancy. We present a well-validated, brief scale to screen pregnant women for clinical depression. Whether this study will generalize to women who do not have a history of major depression remains to be studied.


Low abundance of NDUFV2 and NDUFS4 subunits of the hydrophilic complex I domain and VDAC1 predicts mammalian longevity.
Mitochondrial reactive oxygen species (ROS) production, specifically at complex I (Cx I), has been widely suggested to be one of the determinants of species longevity. The present study follows a comparative approach to analyse complex I in heart tissue from 8 mammalian species with a longevity ranging from 3.5 to 46 years. Gene expression and protein content of selected Cx I subunits were analysed using droplet digital PCR (ddPCR) and western blot, respectively. Our results demonstrate: 1) the existence of species-specific differences in gene expression and protein content of Cx I in relation to longevity; 2) the achievement of a longevity phenotype is associated with low protein abundance of subunits NDUFV2 and NDUFS4 from the matrix hydrophilic domain of Cx I; and 3) long-lived mammals show also lower levels of VDAC (voltage-dependent anion channel) amount. These differences could be associated with the lower mitochondrial ROS production and slower aging rate of long-lived animals and, unexpectedly, with a low content of the mitochondrial permeability transition pore in these species.


Survival implications of sudden functional decline as a sentinel event using the palliative performance scale.
This retrospective study analyzed sudden functional decline using the Palliative Performance Scale (PPSv2) for patients recently admitted to a palliative care unit (PCU) to determine if this adversely affects survival. There were 3328 patients in the cohort over a 13-year period admitted to a tertiary palliative care bed (71.1%) or a residential hospice bed (28.9%). Patient age ranged from 17-102 years old with 51.9% female and 48.1% male; the majority (88.3%) had a cancer diagnosis. Given several limitations noted in the study, six preliminary findings emerged: (1) The lower the initial PPS at PCU admission, the higher the likelihood of an abrupt drop occurring shortly after admission; (2) An abrupt decline in function appears to be associated with smaller survival probabilities; (3) A greater increment change in PPS may be associated with shorter survival probabilities; (4) The lower the PPS on admission, the shorter the survival; (5) When dropping a specific increment amount, the new survival projection appears similar to the PPS level dropped to; and (6) Sudden or abrupt functional decline may be a sentinel event. The data provide evidence that abrupt functional decline implies the likelihood of shorter survival in palliative care patients and may act as a sentinel marker. It is unclear whether these findings would be generalizable outside of a PCU. These results should be interpreted with caution as a prospective evaluation is needed to confirm the results. If substantiated, it may be that incorporating sudden functional decline into palliative prognostic models may increase their predictive accuracy.


Hapten-specific murine colony-forming B cells. II. Delineation of a tolerogen-sensitive subpopulation of colony-forming B cells.
B cell subpopulations were studied by using B cell cloning procedures and an in vitro tolerance induction model. Fluorescein- (FL) specific B cells from normal spleens were isolated by using FL gelatin plates and were then cultured in semisolid agar in the presence or absence of tolerogen. Hapten-specific cells grew in soft agar to form discrete colonies. Colony growth is dependent on "mitogens" present in agar, sheep red blood cells (SRBC), and lipopolysaccharide (LPS). For example, SRBC plus LPS potentiate the growth of an increased number of colony-forming B cells (CFU-B) compared to either additive alone. These CFU-B could be triggered by a specific antigen to yield plaque-forming cells (PFC). With tolerogen (FL-sheep gamma-globulin) present in the agar, the number of FL-specific CFU-B was reduced by 25 to 50%. The ability of the remaining colonies to form PFC upon antigenic stimulation was also reduced. This reduction in CFU-B numbers, however, was observed only when the agar contained both SRBC and LPS as mitogenic potentiators of growth; no effect of tolerogen on CFU-B numbers was seen when cells were grown with either additive alone. Interestingly, the effect of tolerogen on CFU-B numbers was abrogated when peritoneal macrophages, in addition to SRBC plus LPS, were present during cloning. It is postulated that unique subpopulations of B cells form colonies under varied cloning conditions and that those CFU-B grown with SRBC plus LPS display an increased sensitivity to growth inhibition by tolerogen.


amyP, a reporter gene to study strain degeneration in Clostridium acetobutylicum ATCC 824.
Clostridium acetobutylicum produces an extracellular alpha-amylase when grown on glucose as the sole carbon source. This enzyme was previously characterized from a biochemical point of view but its encoding gene was never identified. The 2283-bp amyP gene encodes a 83013-Da mature protein with an N-terminal domain that exhibits strong identity to the family 13 glycosyl hydrolases such as the Bacillus alpha-amylases. Transcriptional analysis revealed that amyP is transcribed in solventogenic but not in acidogenic chemostat cultures. These results are in agreement with the extracellular alpha-amylase activities indicating that the expression of amyP is regulated at the transcriptional level. amyP is located on the pSOL1 megaplasmid that carries all the genes involved in the final steps of solvent formation. Degeneration of C. acetobutylicum has been associated to the loss of pSOL1. We demonstrate here that amyP can be used as a reporter system to quantitatively follow this phenomenon.


Influence of glucose on the sodium content of beta-cell-rich pancreatic islets exposed to sulphonamides and amiloride.
Sodium was measured in beta-cell-rich pancreatic islets isolated from ob/ob-mice starved overnight. Exposure to glucose (5 or 20 mmol/l) resulted in about a 30% reduction of the sodium content whether or not the Na+/K+ pump was inhibited by removal of K+. The glucose effect was not potentiated after amiloride depression of Na+/H+ exchange, and it disappeared when combining removal of K+ with the addition of the hyperglycemic sulphonamide diazoxide (400 mumol/l). Tolbutamide (100 mumol/l) counteracted the reduction of sodium obtained with 5 mmol/l glucose both in the presence or absence of extracellular K+. It is concluded that closure of ATP-regulated K+ channels does not necessarily result in a lowering of the sodium content. The pancreatic beta-cells can be regarded as exceptional among the excitable cells in not responding to their natural physiological stimulus (glucose) with increase of sodium.


Dissociated crossed aphasia: a challenging language representation disorder.
A monolingual strongly right-handed woman developed a left hemiparesis and severe motor aphasia following a right middle cerebral artery infraction, whereas comprehension was entirely intact. She had a history of a transient cerebrovascular event characterized by right hemiparesis and fluent sensory aphasia. This case suggests a transhemispheric pattern of language organization in which the Broca area resides in the right hemisphere, whereas the Wernicke area is in the left.


The bone degenerative processes in senile fishes from Holocene Brazilian shell mounds.
Zooarchaeological collections from shell mounds in Rio de Janeiro (2,470-4,632 cal BP) contain a high prevalence of swollen fish bones belonging to the Atlantic spadefish (Chaetodipterus faber), crevalle jack (Caranx hippos) and fat snook (Centropomus parallelus). Given the lack of knowledge of the bone degenerative process in senile fishes, this study analysed hyperostotic bone in zooarchaeological and modern specimens to obtain high-resolution morphology and microstructure reconstruction. We used microCT as well as X-ray diffraction to characterize the crystallographic changes associated with fish senility. Our results showed that trabecular microstructures in hyperostotic bones were consistent with estimated values of the per cent bone volume-to-total volume ratio (BV/TV) and were greater than 60% in cortical bone. Hyperostotic bones indicated a high radiograph density, and X-ray diffractograms showed a decrease in hydroxyapatite [Ca10 (PO4 )6 (OH)2 ] and calcite (CaCO3 ) neocrystallization. These crystalline and density changes revealed an advanced stage of fish senile and indicate the vulnerability of ageing fish populations.


Case series of scleral patch grafts during COVID-19 pandemic.
Scleral graft is done for clinical conditions as scleral melt post pterygium surgery, immune or infection related scleral melt, for covering the tubes of Ahmed glaucoma valve implant, for covering the orbital implants post enucleation, etc. A review of literature revealed the use of sclera for corneal perforations in the past, but became obsolete after the cornea being used for patch grafts. Now in this COVID-19 time, due to scarcity of corneal tissue, this technique of scleral patch grafts can be considered as an alternative to corneal patch grafts, which serves well the tectonic/therapeutic purpose and helps salvage the eye.


A review on comparative mechanistic studies of antimicrobial peptides against archaea.
Archaea was until recently considered as a third domain of life in addition to bacteria and eukarya but recent studies support the existence of only two superphyla (bacteria and archaea). The fundamental differences between archaeal, bacterial, and eukaryal cells are probably the main reasons for the comparatively lower susceptibility of archaeal strains to current antimicrobial agents. The possible emerging pathogenicity of archaea and the role of archaeal methanogens in methane emissions, a potent greenhouse gas, has led many researchers to examine the sensitivity patterns of archaea and make attempts to find agents that have significant anti-archaeal activity. Even though antimicrobial peptides (AMPs) are well known with several published reviews concerning their mode of action against bacteria and eukarya, to our knowledge, to date no reviews are available that focus on the action of these peptides against archaea. Herein, we present a review on all the peptides that have been tested against archaea. In addition, in an attempt to shed more light on possible future work that needs to be performed we have included a brief overview of the chemical characteristics, spectrum of activity, and the known mechanism of action of each of these peptides against bacteria and/or fungi. We also discuss the nature of and key physiological differences between Archaea, Bacteria, and Eukarya that are relevant to the development of anti-archaeal peptides. Despite our relatively limited knowledge about archaea, available data suggest that AMPs have an even broader spectrum of activity than currently recognized.


Information search and decision making: effects of age and complexity on strategy use.
The impact of task complexity on information search strategy and decision quality was examined in a sample of 135 young, middle-aged, and older adults. We were particularly interested in the competing roles of fluid cognitive ability and domain knowledge and experience, with the former being a negative influence and the latter being a positive influence on older adults' performance. Participants utilized 2 decision matrices, which varied in complexity, regarding a consumer purchase. Using process tracing software and an algorithm developed to assess decision strategy, we recorded search behavior, strategy selection, and final decision. Contrary to expectations, older adults were not more likely than the younger age groups to engage in information-minimizing search behaviors in response to increases in task complexity. Similarly, adults of all ages used comparable decision strategies and adapted their strategies to the demands of the task. We also examined decision outcomes in relation to participants' preferences. Overall, it seems that older adults utilize simpler sets of information primarily reflecting the most valued attributes in making their choice. The results of this study suggest that older adults are adaptive in their approach to decision making and that this ability may benefit from accrued knowledge and experience.