Attitudes and attitude strength as precursors to object attachment.
This article puts forth a perspective that attitudes and attitude strength can serve as precursors to object attachment. To help the reader understand this perspective, I provide an overview of the attitude and attitude strength constructs and distinguish them from object attachment. I then explain a number of prominent ways in which attitudes and attitude strength can influence behaviors that might be important contributors to object attachment. In doing so, this paper offers researchers interested in object attachment an alternative lens to study how people might come to be attached to their objects.


Helicobacter pylori infection induces stem cell-like properties in Correa cascade of gastric cancer.
Gastric cancer (GC) is the fourth leading cause of cancer-related death. Its poor prognosis is attributed to unclear pathogenesis. Currently, the most widely accepted model for elucidating the mechanism of GC is the Correa cascade, which covers several histological lesions of the gastric mucosa. GC stem cells (CSCs) are crucial for oncogenesis in the Correa cascade and GC progression. As Helicobacter pylori (H. pylori) is the etiological factor in the Correa cascade, growing evidence suggests that enhancement of gastric stem cell-like properties and increase in CSCs correlate with H. pylori infection. In this paper, we review recent studies that present pathogenic mechanisms by which H. pylori induces gastric stem cell-like properties and CSCs, which may supplement the existing Correa model of GC. First, the dysfunction of developmental signaling pathways associated with H. pylori infection leads to the enhancement of gastric stemness. Second, H. pylori infection promotes alteration of the gastric mucosal microenvironment. In addition, epithelial-mesenchymal transition (EMT) may contribute to H. pylori-induced gastric stemness. Taken together, understanding these pathogeneses will provide potential therapeutic targets for the treatment of CSCs and malignant GC in H. pylori induced-Correa cascade of GC.


Homogeneous restriction fragment length polymorphism analysis of the ribosomal DNA repeating unit in New World Leishmania.
We have studied the Sau 3AI restriction length polymorphisms (RFLP) of the non-transcribed ribosomal spacer of Leishmania isolates from the mexicana and braziliensis complexes, using cloned sequences of Leishmania garnhami and Leishmania braziliensis. The L. garnhami probe produced very complex but conserved patterns in the homologous organisms, and these were shared by all the mexicana complex isolates at intermediate stringency conditions. The small subunit rRNA coding region within the probe also revealed a polymorphic Sau 3AI site exclusive of the braziliensis isolates. The braziliensis probe, containing only spacer sequences, yielded simple and very homogeneous patterns in all braziliensis isolates regardless of their geographical origin. Two main groups are identified in the New World isolates by the RFLP analysis in coincidence with the accepted mexicana and braziliensis complexes.


Effect of various storage conditions on the stability of quinolones in raw milk.
Research on the storage stability of antibiotic residues in milk is important for method development or validation, milk quality control and risk assessment during screening, confirmation, qualitative or quantitative analysis. This study was conducted using UPLC-MS/MS to determine the stability of six quinolones - ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), difloxacin (DIF) and flumequine (FLU) - in raw milk stored under various conditions to investigate if quinolones degrade during storage of milk, and finally to determine optimal storage conditions for analysis and scientific risk assessment of quinolone residues in raw milk. The storage conditions included different temperatures and durations (4°C for 4, 8, 24 and 48 h; -20°C for 1, 7 and 30 days; -80°C for 1, 7 and 30 days), thawing temperatures (25, 40 and 60°C), freeze-thaw cycles (1-5), and the addition of different preservatives (sodium thiocyanate, sodium azide, potassium dichromate, bronopol and methanal). Most quinolones exhibited high stability at 4°C for up to 24 h, but began to degrade after 48 h. In addition, no degradation of quinolones was seen when milk samples were stored at -20°C for up to 7 days; however, 30 days of storage at -20°C resulted in a small amount of degradation (about 30%). Similar results were seen when samples were stored at -80°C. Moreover, no losses were observed when frozen milk samples were thawed at 25, 40 or 60°C. All the quinolones of interest, except sarafloxacin, were stable when milk samples were thawed at 40°C once and three times, but unstable after five freeze-thaw cycles. Preservatives affected the stability of quinolones, but the effects differed depending on the preservative and quinolone. The results of this study indicate optimum storage protocols for milk samples, so that residue levels reflect those at the time of initial sample analysis, and should improve surveillance programmes for quinolones in raw milk.


Association of caveolin-1 genotypes with nasopharyngeal carcinoma susceptibility in Taiwan.
Caveolin-1 (Cav-1), which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. High expression of Cav-1 in nasopharyngeal carcinoma (NPC) may enhance tumor cell migration and correlate with poor prognosis of the patients, while the genetic alterations of Cav-1 during nasopharyngeal carcinogenesis are still largely unknown. The aim of this study was to evaluate the association between NPC susceptibility and Cav-1 genotypes. One hundred and seventy six patients with NPC and 176 age- and gender-matched healthy controls recruited in Taiwan were genotyped and analyzed by PCR-restriction fragment length polymorphism. There were significant differences between the NPC and control groups in the distributions of the genotypic (p=0.0019) and allelic frequencies (p=2.5 10(-4)) in the Cav-1 T29107A (rs7804372) polymorphism. In this first report of Cav-1 involvement in NPC the A allele of Cav-1 T29107A is found to be protective against the development of NPC and may be a novel useful genomic marker for early screening and prediction of NPC.


Epidemiology of paediatric minor head injury: Comparison of injury characteristics with Indices of Multiple Deprivation.
Head injury (HI) is a common presentation to Child Emergency Departments (CEDs), but the actual number of children attending with minor HI is unclear. Most research has focussed on admitted patients, often relying on hospital-coded admission data. We studied the incidence of minor HI presenting to the CED of a major teaching hospital in Coventry and Warwickshire. HI attendances were compared with population data to identify injury patterns relating to deprivation. All CED admissions were screened by the research team, and data on minor head injuries (GCS 13-15) collected prospectively from 1st January until 31st August 2011. Information was collected on demographics, ethnicity, cause and severity of injury, injury location (in or outside the home), other injuries and mode of arrival. Deprivation data were obtained by cross-referencing postcodes with English Indices of Multiple Deprivation (IMD 2010). For comparison, the hospital audit department provided figures for coded head injuries during the same period. During the 8 month period, hand-searching identified 1747 children with minor HI, aged between 0 and 16 years. Of these 99% had minimal HI (GCS 15 or 'alert'). In the same period, hospital-coded minor HIs numbered only 1081. HIs formed 9% of all CED attendances. Thirteen children returned to the CED with worrying symptoms after discharge home. Approximately 3.4% of the local paediatric population attend the CED with HI per year (3419/100,000 population). Falls accounted for 62% of HIs overall, rising to 77% in children aged 0-5. Most in-home head injuries (81%) were the result of falls (p<0.0001). Significantly more injuries took place inside the home for 0-5 year olds (58%) than for older children (20%) (p<0.0001). Children living in the most deprived areas were more likely to attend the CED with HI (RR: 1.19; CI: 1.06-1.35, p=0.004), and arrive using emergency services (OR: 1.77; CI: 1.30-2.40, p<0.001). There were no significant differences between the deprived and non-deprived groups for location or cause of injury. Young children are particularly at risk of HI and parents should be offered information on injury prevention. More children from deprived areas attended with HI and these families may benefit most from targeted interventions.


Immunoelectrophoretic analysis of renal and intestinal brush border converting enzyme.
Antibodies raised against purified hog renal or intestinal brush border protein or against purified hog kidney angiotensin I converting enzyme (ACE) were used to characterize renal and intestinal brush border ACE by techniques of differential solubilization, fused-rocket, line absorption and crossed-immunoelectrophoresis. Renal ACE is immunologically identical to intestinal ACE. ACE is present as a major intrinsic protein of renal brush border and a minor intrinsic protein of intestinal brush border. Renal and intestinal brush border ACE could be solubilized by detergent and/or papain. The electrophoretic mobilities of the papain-treated forms of ACE were greater than the detergent-treated forms. This increased mobility was associated with the removal of a small, non-antigenic component of the enzyme. Thus, like several other intrinsic brush border peptidases, ACE is bound to renal and intestinal brush border by a small hydrophobic anchor.


Beyond skin deep: shedding light on the neuropsychiatric consequences of Monkeypox (Mpox).
This review is attempted in view of World Health Organization (WHO) warning on Monkeypox virus (Mpox) to summarize the available data regarding the potential effect on central nervous system (CNS), its complications, and diagnostic methods. We combed various international databases (including Scopus, PubMed, Web of Science, and Google Scholar) for articles mentioning Mpox infection, orthopox infection, and the central nervous system that were published between the years 2000 and 2022. Further evidence was evaluated from relevant studies published in the literature. There is emerging evidence of central nervous system neurological involvement. In addition to encephalopathy, which is one of the most serious neurological complications of Mpox, the most common complications of Mpox infection are headache, weakness, myalgia, anorexia, and altered consciousness. Anxiety and depression have also been identified as the most common psychiatric symptoms in these patients.


Postprandial increases in nitrogenous excretion and urea synthesis in the Chinese soft-shelled turtle, Pelodiscus sinensis.
The objective of this study was to determine the effects of feeding on the excretory nitrogen (N) metabolism of the aquatic Chinese soft-shelled turtle, Pelodiscus sinensis, with a special emphasis on the role of urea synthesis in ammonia detoxification. P. sinensis is ureogenic and possesses a full complement of ornithine-urea cycle enzymes in its liver. It is primarily ureotelic in water, and the estimated rate of urea synthesis in unfed animals was equivalent to only 1.5% of the maximal capacity of carbamoyl phosphate synthetase I (CPS I) in its liver. Approximately 72 h was required for P. sinensis to completely digest a meal of prawn meat. During this period, there were significant increases in ammonia contents in the stomach at hour 24 and in the intestine between hours 12 and 36, which could be a result of bacterial activities in the intestinal tract. However, ammonia contents in the liver, muscle, brain and plasma remained unchanged throughout the 72-h post-feeding. In contrast, at hour 24, urea contents in the stomach, intestine, liver, muscle, brain and plasma increased significantly by 2.9-, 3.5-, 2.6-, 2.9-, 3.4 and 3.0-fold, respectively. In addition, there was a 3.3- to 8.0-fold increase in the urea excretion rate between hours 0 and 36 post-feeding, which preceded the increase in ammonia excretion between hours 12 and 48. By hour 48, 68% of the assimilated N from the feed was excreted, 54% of which was excreted as urea-N. The rate of urea synthesis apparently increased sevenfold during the initial 24 h after feeding, which demanded only 10% of the maximal CPS I capacity in P. sinensis. The postprandial detoxification of ammonia to urea in P. sinensis effectively prevented postprandial surges in ammonia contents in the plasma and other tissues, as observed in other animals, during the 72-h period post-feeding. In addition, postprandial ammonia toxicity was ameliorated by increased transamination and synthesis of certain amino acids in the liver and muscle of P. sinensis. After feeding, a slight but significant increase in the glutamine content occurred in the brain at hour 24, indicating that the brain might experience a transient increase in ammonia and ammonia was detoxified to glutamine.


A TRIZ-inspired bat algorithm for gene selection in cancer classification.
Gene expression data are expected to make a great contribution in the producing of efficient cancer diagnosis and prognosis. Gene expression data are coded by large measured genes, and only of a few number of them carry precious information for different classes of samples. Recently, several researchers proposed gene selection methods based on metaheuristic algorithms for analysing and interpreting gene expression data. However, due to large number of selected genes with limited number of patient's samples and complex interaction between genes, many gene selection methods experienced challenges in order to approach the most relevant and reliable genes. Hence, in this paper, a hybrid filter/wrapper, called rMRMR-MBA is proposed for gene selection problem. In this method, robust Minimum Redundancy Maximum Relevancy (rMRMR) as filter to select the most promising genes and an modified bat algorithm (MBA) as search engine in wrapper approach is proposed to identify a small set of informative genes. The performance of the proposed method has been evaluated using ten gene expression datasets. For performance evaluation, MBA is evaluated by studying the convergence behaviour of MBA with and without TRIZ optimisation operators. For comparative evaluation, the results of the proposed rMRMR-MBA were compared against ten state-of-arts methods using the same datasets. The comparative study demonstrates that the proposed method produced better results in terms of classification accuracy and number of selected genes in two out of ten datasets and competitive results on the remaining datasets. In a nutshell, the proposed method is able to produce very promising results with high classification accuracy which can be considered a promising contribution for gene selection domain.


Response of the human vestibulo-ocular reflex following long-term 2x magnified visual input.
This study examines the contribution of predictive motor programming to the adjustment of vestibulo-ocular reflex (VOR) gains after exposure to spectacles with a 2X magnification. When fully adapted, subjects exhibited two-fold gain increases with a 3 Hz sinewave stimulus with both an imaginary earth-fixed and imaginary moving target. Before complete adaptation was achieved, quick phases embedded in the slow component were observed intermittently which compensated for insufficient VOR gain. At 0.5 Hz in the same state of full adaptation during fixation of an imaginary earth-fixed target subjects exhibited a gain increase of only approximately 75% indicating that the contribution of VOR adjustment is not sufficient for perfect visual stabilization at lower frequencies. Over the range of random stimulation (0.5-5 Hz), the VOR failed to exhibit complete adaptation. The degree of adaptation derived with a VOR-cancellation task was less overall than that with a task requiring perfect compensatory eye movements. These findings indicate that central motor programmes are required in the adaptive process to achieve visual stability.


Should patients who have persistent severe symptoms receive a left ventricular assist device or cardiac resynchronization therapy as the next step?
Currently, cardiac resynchronization therapy (CRT) should be considered before a left ventricular assist device for most patients who have moderate or severe left ventricular systolic dysfunction and have not responded symptomatically to conventional pharmacologic measures. There is little evidence that the severity of cardiac dyssynchrony as measured using current techniques is useful in predicting the benefits of CRT. QRS duration on the surface ECG is a surrogate marker of the severity of the left ventricular ejection fraction as well as of several types of dyssynchrony. More clinical trials are required to determine whether excluding patients who have QRS duration less than 120 msec or those who have no evidence of dyssynchrony from implantation of CRT is appropriate. Perhaps all patients who have moderate or severe left ventricular systolic dysfunction should be considered for CRT, either to improve symptoms if they are persistent or relapsing, or to improve outcome. In the longer-term future, it is possible that the development of less expensive, small, and safe left ventricular assist devices will supplant the role of both CRT and CRT-defibrillator devices.


The serological response of cattle immunized with Yersinia enterocolitica O:9 or O:16 to Yersinia and Brucella abortus antigens in enzyme immunoassays.
Sera from calves immunized with Yersinia enterocolitica serotypes O:9 or O:16 were tested by indirect enzyme linked immunosorbent assay (ELISA) using lipopolysaccharide (LPS) preparations from Brucella abortus or Y. enterocolitica O:9 or O:16 for their antibody content of the IgG1 or IgG2 subclasses. High IgG1 responses were present with the three antigens in both groups although some individual variations between animals were noted. The IgG2 responses were modest and in some cases not above background 'noise'. Thus IgG2 antibody was not measurable in sera from serotype O:9 injected calves when using serotype O:16 LPS or in serotype O:16 injected calves when using B. abortus or serotype O:9 LPSs. A competitive ELISA using B. abortus O-polysaccharide and a monoclonal antibody to B. abortus LPS (initially designed to differentiate the antibody responses of cattle naturally infected with B. abortus from those vaccinated with strain 19) was used on sera from both groups of calves. Using this test, no antibody was detected in the group immunized with serotype O:16 and except for one animal in the serotype O:9 immunized group, only low levels of antibody were transiently in evidence. One animal in this group responded with quite high levels of competing antibody which, however, declined towards the end of the test period. The competitive ELISA may prove a useful serological tool for differentiating vaccinal and field infection titers to B. abortus and also to eliminate cross-reactions observed with Y. enterocolitica serotypes.


Polyclonal and monoclonal antibodies to the interferon-inducible protein Mx of influenza virus-resistant mice.
Interferon-alpha/beta induces in cells from mice carrying the influenza virus resistance allele Mx+ the synthesis of a unique 75,000-dalton protein (designated here protein Mx) that was not detectable in interferon-treated cells from Mx- mice lacking the resistance allele (Horisberger, M. A., Staeheli, P., and Haller, O. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 1910-1914). We have immunized Mx- BALB/c mice with extracts of interferon-treated cells from congenic Mx+ BALB X A2G-Mx mice. Resulting hyperimmune sera immunoprecipitated a single interferon-inducible 75,000-dalton protein of Mx+ embryo cells. Sera did not react with any interferon-inducible protein of Mx- cells. Synthesis of the immunoprecipitable 75,000-dalton protein Mx was induced by interferon-alpha/beta but not by interferon-gamma in Mx+ cells of diverse genetic backgrounds. Monoclonal antibodies to protein Mx were selected in similar immunoprecipitation assays. One discrete in vitro translation product of relevant mRNA reacted with polyclonal and monoclonal antibodies and was indistinguishable from in vivo synthesized protein Mx.


The incidence, hospitalisations and deaths in acutely ill children with dysnatraemias.
The aim was to evaluate the incidence, hospitalisations and deaths in acutely ill children with dysnatraemias. This was a register-based cohort study of 46 518 acutely ill children aged <16 years who visited a paediatric emergency department. Risk factors were assessed using two nested case-control studies. Moderate to severe hypernatraemia occurred in 92 children (0.20%; 95% confidence interval [CI]: 0.16%-0.24%) and moderate to severe hyponatraemia in 131 children (0.28%; 95% CI: 0.24%-0.33%). Underlying medical conditions increased the risk of both moderate to severe hypernatraemia (odds ratio [OR]: 17; 95% 5.5-51) and moderate to severe hyponatraemia (OR: 3.5; 95% CI: 2.0-5.9). The use of a feeding tube (OR: 14; 95% CI: 3.2-66) and intellectual disability (OR: 7.3; 95% CI: 3.0-18) was associated with moderate to severe hypernatraemia. The risk of death was associated with moderate to severe hypernatraemia (OR: 19; 95% CI: 2.0-2564) and moderate to severe hyponatraemia (OR: 33; 95% CI: 3.7-4311). Severe dysnatraemias were more prevalent in acutely ill children with underlying medical conditions and were markedly associated with the risk for death.


Some current dimensions of the behavioral economics of health-related behavior change.
Health-related behaviors such as tobacco, alcohol and other substance use, poor diet and physical inactivity, and risky sexual practices are important targets for research and intervention. Health-related behaviors are especially pertinent targets in the United States, which lags behind most other developed nations on common markers of population health. In this essay we examine the application of behavioral economics, a scientific discipline that represents the intersection of economics and psychology, to the study and promotion of health-related behavior change. More specifically, we review what we consider to be some core dimensions of this discipline when applied to the study health-related behavior change. Behavioral economics (1) provides novel conceptual systems to inform scientific understanding of health behaviors, (2) translates scientific understanding into practical and effective behavior-change interventions, (3) leverages varied aspects of behavior change beyond increases or decreases in frequency, (4) recognizes and exploits trans-disease processes and interventions, and (5) leverages technology in efforts to maximize efficacy, cost effectiveness, and reach. These dimensions are overviewed and their implications for the future of the field discussed.


The X-ray structure of the NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase from Saccharomyces cerevisiae.
Eucaryotes possess one or more NADP-dependent methylene-THF dehydrogenases as part of multifunctional enzymes. In addition, yeast expresses an unusual monofunctional NAD-dependent enzyme, yMTD. We report X-ray structures for the apoenzyme and its complex with NAD+ at 2.8 and 3.0 A resolution, respectively. The protein fold resembles that seen for the human and Escherichia coli dehydrogenase/cyclohydrolase bifunctional enzymes. The enzyme has two prominent domains, with the active site cleft between them. yMTD has a noncanonical NAD-binding domain that has two inserted strands compared with the NADP-binding domains of the bifunctional enzymes. This insert precludes yMTD from dimerizing in the same way as the bifunctional enzymes. yMTD functions as a dimer, but the mode of dimerization is novel. It does not appear that the difference in dimerization accounts for the difference in cofactor specificity or for the loss of cyclohydrolase activity. These functional differences are probably accounted for by minor differences within the tertiary structure of the active site of the monomeric protein.


Influence of bio-aging on corrosion behavior of different implant materials.
Dental implants and abutments are exposed to challenging oral environment. Corrosion of these materials can affect the overall performance of titanium implants. To investigate the effects of biofilm-induced bio-aging on corrosion behavior of different implant materials surface. Commercial polished titanium (Polish), sand-blasted, large grit, acid-etched surface treated titanium (SLA), microarc oxidation (MAO), and hydroxyapatite (HA) coated titanium were bio-aged with saliva biofilm for 30 days. Titanium surfaces topography, chemical composition, roughness, and water contact angle changes were evaluated. In addition, human gingival fibroblasts (HGFs) adhesion, Streptococcus sanguinis (S. sanguinis) biofilm formation were determined. Surface topography, roughness, and chemical composition have no significant changes for all groups after bio-aging (P > .05). Water contact angle of bio-aged SLA was greatly increased (P < .05). While other groups showed no sign of change (P > .05). Adhesion and proliferation of HGFs on the bio-aged SLA titanium surfaces were decreased (P < .05), but increased on bio-aged Polish and HA titanium (P < .05). S. sanguinis biofilm viability was promoted with bio-aging in HA group (P < .05). Biological characteristics of Polish, SLA, and HA titanium surfaces were influenced by bio-aging. While MAO group was relatively resistant to saliva biofilm bio-aging.


Synthesis, resolution and crystal structures of two enanti-omeric rhodamine derivatives.
The title mol-ecule, rac-6'-bromo-3'-di-ethyl-amino-3H-spiro-[2-benzo-furan-1,9'-xanthen]-3-one, C24H20BrNO3, was synthesized and the two enanti-omers which formed were separated. The structures of all three compounds were determined and compared with those of a variety of related derivatives. A notable feature is the fold of the xanthene portion which ranges from 15.15 (13)° in the racemate to 2.42 (2)° in one mol-ecule of the R enanti-omer with that for the S enanti-omer having an inter-mediate value. The differences are attributed to the number and severity of inter-molecular inter-actions which include C-H⋯O hydrogen bonds, C-H⋯π(ring) and, in the S enanti-omer, a π-stacking inter-action between the carbonyl group and an aromatic ring.


Synthesis, photobiological activity and photoreactivity of methyl-thieno-8-azacoumarins, novel bioisosters of psoralen.
4,4'-dimethyl-thieno-8-azacoumarin (6) and 4,4',5'-trimethyl-thieno-8-azacoumarin (8) were synthesised. Their photobiological activity was tested on human tumour cell lines. Interestingly, for 6, a photocytotoxic ability higher in HL-60, comparable in HeLa cells, with respect to that of the well-known drug 8-methoxypsoralen (8-MOP), was demonstrated. The covalent photoaddition to DNA occurs by means of the molecular mechanism already demonstrated for furocoumarins. However, it is noteworthy that no skin phototoxicity appears.


Effect of lipoteichoic acid on IL-2 and IL-5 release from T lymphocytes in asthma and COPD.
Susceptibility to infections with gram-positive bacteria, which are an important trigger of exacerbations, is increased in COPD and asthma. Unraveling the underlying mechanisms may help developing therapeutic strategies to reduce exacerbation rates. The aim of this study was to evaluate the effects of lipoteichoic acid (LTA), a danger signal from gram-positive bacteria, on T cell cytokines related to bacterial infection defense in COPD and asthma. T cell populations within peripheral blood mononuclear cells (PBMCs) were ex-vivo activated towards T(H)2/T(C)2 subtypes and subsequently stimulated with LTA. IL-2 and IL-5 concentrations in cell culture supernatants were measured by ELISA comparative between non-smokers (NS), current smokers without airflow limitation (S), smokers with moderate to severe COPD and mild to moderate asthmatics (A) (each n=10). IL-2 and IL-5 baseline levels were without differences between the cohorts. After T cell activation, IL-2 and IL-5 releases were increased in all cohorts, however, for IL-2 this increase was significantly higher in S and by trend in COPD compared to the other groups. LTA time-dependently suppressed IL-2 release in NS, S and COPD but not in A. LTA reduced IL-5 release in COPD and A but not in NS and S. Summarized, LTA reduces T(H)2/T(C)2 cytokines indicating immunosuppressive effects, which are dysregulated in COPD and asthma. This implies a misguided response to gram-positive bacterial infections, which might help to explain the increased susceptibility to bacterial infections in COPD and asthma.


Persistent mesonephric duct found at laparoscopy for impalpable testis.
Laparoscopy is an increasingly popular choice for treatment of the impalpable testis. There are many anatomical variants that may be found at operation. We present a case of a 1-year-old boy who presented with an impalpable right testis and absent right kidney, and at laparoscopy was found to have a persistent mesonephric duct. Awareness of this variation allowed for adequate excision and subsequent investigations.


Regulatory T-cell dysfunction and its implication for cell therapy.
Regulatory T cells (Tregs) are a subtype of CD4+ T cells that can mediate immune tolerance by a multitude of immunomodulatory mechanisms. Treg-based adoptive immunotherapy is currently being tested in multiple phases I and II clinical trials in transplantation and autoimmune diseases. We have learned from the work done on conventional T cells that distinct mechanistic states can define their dysfunctions, such as exhaustion, senescence, and anergy. All three can negatively impact the therapeutic effectiveness of T-cell-based therapies. However, whether Tregs are susceptible to such dysfunctional states is not well studied, and results are sometimes found to be controversial. In addition, Treg instability and loss of FOXP3 expression is another Treg-specific dysfunction that can decreasein their suppressive potential. A better understanding of Treg biology and pathological states will be needed to compare and interpret the results of the different clinical and preclinical trials. We will review herein Tregs' mechanisms of action, describe different T-cell dysfunction subtypes and how and if they apply to Tregs (exhaustion, senescence, anergy, and instability), and finally how this knowledge should be taken into consideration when designing and interpreting Treg adoptive immunotherapy trials.


Functional postural-stabilization tests according to Dynamic Neuromuscular Stabilization approach: Proposal of novel examination protocol.
This paper presents a set of eleven functional Dynamic Neuromuscular Stabilization (DNS) tests corresponding with specific infantile developmental stages, clarifying desired postural-locomotion patterns from a developmental perspective, while also describing frequently-observed disturbances of these patterns.


Contractile filaments in cells of regenerating tendon.
An extensive cytoplasmic fibrillar system has been observed in fibroblast-like cell of regenerating tendon. It consists of bundles of actin filaments, which often show a cross-striated appearance due to electron dense bodies occurring throughout their length. The functional role of this contractile apparatus seems to be related to the process of movement and orientation of the newly formed cells and to the retraction of the regenerating tendon.


Inhibition of the RacGEF VAV3 by the small molecule IODVA1 impedes RAC signaling and overcomes resistance to tyrosine kinase inhibition in acute lymphoblastic leukemia.
Aberrant RHO guanine nucleotide exchange factor (RhoGEF) activation is chief mechanism driving abnormal activation of their GTPase targets in transformation and tumorigenesis. Consequently, a small-molecule inhibitor of RhoGEF can make an anti-cancer drug. We used cellular, mouse, and humanized models of RAC-dependent BCR-ABL1-driven and Ph-like acute lymphoblastic leukemia to identify VAV3, a tyrosine phosphorylation-dependent RacGEF, as the target of the small molecule IODVA1. We show that through binding to VAV3, IODVA1 inhibits RAC activation and signaling and increases pro-apoptotic activity in BCR-ABL1-transformed cells. Consistent with this mechanism of action, cellular and animal models of BCR-ABL1-induced leukemia in Vav3-null background do not respond to IODVA1. By durably decreasing in vivo RAC signaling, IODVA1 eradicates leukemic propagating activity of TKI-resistant BCR-ABL1(T315I) B-ALL cells after treatment withdrawal. Importantly, IODVA1 suppresses the leukemic burden in the treatment refractory pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models better than standard-of-care dasatinib or ponatinib and provides a more durable response after treatment withdrawal. Pediatric leukemia samples with diverse genetic lesions show high sensitivity to IODVA1 ex vivo and this sensitivity is VAV3 dependent. IODVA1 thus spearheads a novel class of drugs that inhibits a RacGEF and holds promise as an anti-tumor therapy.


Kidney transplantation from hepatitis B surface antigen-positive donors into hepatitis B surface antigen-positive recipients: preliminary findings.
The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our initial experience in transplanting kidneys from hepatitis B surface antigen (HbsAg)-positive donors into HbsAg-positive recipients. From January 2002 to March 2004, 5 patients with end-stage renal disease, hepatitis B virus (HBV) infection, and HbsAg seropositivity underwent a kidney transplantation from a cadaveric HbsAg-positive donor. The median time on the waiting list was 8 months, compared with the median of 3 years on the national waiting list. One patient experienced an acute rejection; 1 patient had an increase in serum level of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) with no signs of recurrence of hepatitis. Graft and patient survival at a median follow-up of 12 months was 100%. Although the number of patients is small and the follow-up is short, our results suggest that HbsAg-positive donors can be considered as an alternative donor source because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.


Topical retinoid treatment for various dry-eye disorders.
We evaluated the clinical efficacy of treating various dry-eye disorders using 0.01% and 0.1% (weight/weight) topical all-trans retinoic acid ointment. Twenty-two patients were selected and classified into four major groups: keratoconjunctivitis sicca (6 patients; 11 eyes), Stevens-Johnson syndrome (9 patients; 17 eyes), ocular pemphigoid or drug-induced pseudopemphigoid (3 patients; 6 eyes), and surgery or radiation-induced dry eye (4 patients; 4 eyes), based on the criterion that they remained symptomatic even under maximum tolerable conventional medical and/or surgical therapies. The results indicated that squamous metaplasia with mucin deficiency secondary to goblet cell loss and keratinization may be the basis for the development of clinical symptoms and morbidities, as these epithelial abnormalities were invariably present before treatment. After treatment, all patients demonstrated clinical improvements in symptoms, visual acuity, rose Bengal staining, or Schirmer test. Most importantly, this topical vitamin A treatment caused the reversal of squamous metaplasia as evidenced by impression cytology. Therefore, this treatment may represent the first nonsurgical attempt to treat these disorders by reversing diseased ocular surface epithelium.


Comparison of sequences for depicting bone marrow alterations in osteomyelitis applied in a low field strength magnetic resonance imaging system.
To investigate the efficacy of standard sequences of a low field system for the detection of osteomyelitis, we tested T1wI pre and post i.v. contrast, T2w and fat suppressed IR sequences. On the basis of clinical and laboratory evidence, pathology reports, and three phase granulocyte scintigraphy, osteomyelitis was diagnosed in 18 of 21 patients with Charcot's joints. A consecutive low and high field magnetic resonance (MR) scan confirmed osteomyelitic bone marrow changes in the same osseous regions. These 18 diabetic patients were then studied on a 0.2 Tesla dedicated MR system (Esaote ArtoScan) using T1wI (SE: relaxation time (TR) 520/echo time (TE) 24: axial and coronal) before and after i.v. application of 0.1 mmol/l Gd-DTPA/kg BW, T2w imaging (TSE: TR 3500/TE 80 or TR 2000/TE 120: axial), and fat suppressed inversion recovery (IR) imaging (short tau inversion recovery (STIR): TR 3000/TE 30/TI 80 or inversion recovery gradient echo (IRGE)/fat suppressed IRGE (GEFS): TR 1000/TE 16m 80: coronal). The SE T1w sequence showed a significantly higher contrast-to-noise ratio (CNR) before administration of i.v. contrast. The TSE T2w pulse sequence demonstrated bone marrow changes superiorily utilizing a TE of 120 ms (CNR = 16.5+/-2.7 compared to 5.5+/-2.5 with TE = 80 ms). The IRGE showed a higher CNR than the standard STIR (CNR = 19.2+/-2.5 compared to 12.4+/-2.9). Fat suppressed IRGE imaging and longer TE in T2w TSE sequences result in a significantly better CNR in osteomyelitis. This way, using optimized sequences, low field systems are apt to depict bone marrow changes in the course of osteomyelitis.


Water deficit effects on tomato quality depend on fruit developmental stage and genotype.
Many studies have advocated that water deficit (WD) may exert beneficial effects on fruit quality. However, the fruit response to WD at specific developmental stages was seldom investigated, although different mechanisms could be involved at each stage and lead to different effects on final fruit quality. In the present study, a moderate WD (-60% of water supply compared to control) was applied during each of the three major phases of fruit development, namely cell division (CD), cell expansion (CE) and maturation (MT). Two cocktail tomato (Solanum lycopersicum L.) genotypes were studied, one producing poor quality fruits (LA1420), and the other one producing tasty fruits (PlovdivXXIVa named Plovdiv). Contrasted responses were observed between the two genotypes. For both of them, fruit fresh mass and size were not significantly reduced by WD, whatever the developmental phase affected. Osmotic regulations were likely involved in the CD treatment for LA1420 fruits, which accumulated more sugars (both on a dry and fresh matter basis) and less acids (on a dry matter basis). In the CE treatment, other adaptive strategies involving sugar metabolism and sub-cellular compartmentation were suggested. In contrast, the composition of Plovdiv fruits changed only under the MT treatment, with less sugars, acids and carotenoids compared to control fruits (both on a dry and fresh matter basis). Total ascorbic acid (AsA) was not significantly influenced by treatments in both genotypes. On their whole, results suggest that, depending on genotypes, fruits are sweeter and less acidic under WD, but that the nutritive value related to vitamin and carotenoid contents may be lessened. The sensitivity of each developmental phase highly depends on the genotype. All phases were sensitive to WD for LA1420, but only the ripening phase for Plovdiv. Interestingly, major changes in fruit composition were observed in LA1420 which presents poor fruit quality under control conditions. This suggests the onset of fast adaptive response to WD at the fruit level in this genotype.


Rapid and stain-free quantification of viral plaque via lens-free holography and deep learning.
A plaque assay-the gold-standard method for measuring the concentration of replication-competent lytic virions-requires staining and usually more than 48 h of runtime. Here we show that lens-free holographic imaging and deep learning can be combined to expedite and automate the assay. The compact imaging device captures phase information label-free at a rate of approximately 0.32 gigapixels per hour per well, covers an area of about 30 × 30 mm2 and a 10-fold larger dynamic range of virus concentration than standard assays, and quantifies the infected area and the number of plaque-forming units. For the vesicular stomatitis virus, the automated plaque assay detected the first cell-lysing events caused by viral replication as early as 5 h after incubation, and in less than 20 h it detected plaque-forming units at rates higher than 90% at 100% specificity. Furthermore, it reduced the incubation time of the herpes simplex virus type 1 by about 48 h and that of the encephalomyocarditis virus by about 20 h. The stain-free assay should be amenable for use in virology research, vaccine development and clinical diagnosis.


Surface plasmon resonance: a study of the effect of biotinylation on the selection of antibodies for use in immunoassays.
Surface plasmon resonance is a valuable optical phenomenon for monitoring biomolecular interactions in real time. In this project anti-mouse-Fc was coupled to the carboxymethyl dextran coating on the surface of a CM5 sensor chip (BIAcore) using amine coupling. Monoclonal antibodies (MAbs) to Luteinizing Hormone (LH) were then captured on this surface in the correct orientation for binding. LH (500 IU/l) was injected over the surface and the subsequent binding and dissociation events were monitored. The resulting optical response curves allowed fast analysis of the binding interactions of eight selected MAbs. It was possible to develop a two-site immunometric assay for LH using a pair of these MAbs. The effect of biotinylating the MAbs, using various biotin:antibody coupling ratios, on their subsequent binding to both LH and avidin conjugated alkaline phosphatase was also investigated. This approach has allowed rapid evaluation of the effect of changes in both reagent and reaction conditions on immunoassay performance and appears to be a valuable adjunct to immunosensor and immunoassay development.


Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.
Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.


Alteration of Serum Lipid in Oral Sub Mucous Fibrosis in Central India.
Oral sub mucous fibrosis is the most common precancerous lesion in India. Lipids are the major cell membrane components essential for various biological function including cell growth and division for the maintenance of cell integrity of normal and malignant tissue. Low levels of lipids serves as a marker and prognostic indicator in the early detection of oral precancerous and cancerous states. In spite of high prevalence and its potential to undergo malignant transformation, this condition has not widely been investigated with respect to serum lipid levels. In present study an attempt is made to analyze the complete serum profile, total cholesterol, triglycerides, high density lipoprotein. Low density lipoprotein, and very low density lipoprotein in oral precancerous lesion and control. Study was conducted in 30 clinically and histopathologically diagnosed cases of premalignant lesion and 30 age and sex match controls. The complete lipid profile including TC, TG, HDL, LDL, and VLDL was analyzed. Serum lipid levels were significantly lower in patients with oral lesion than in controls. From the finding it appears that the decreases in the lipid levels may be considered as useful marker in the early diagnosis of oral premalignant lesion.


Novel small RNA-encoding genes in the intergenic regions of Bacillus subtilis.
Small, non-coding RNAs (ncRNAs) perform diverse functions in a variety of organisms, but few ncRNAs have been identified in Bacillus subtilis. To search the B. subtilis genome for genes encoding ncRNAs, we focused on 123 intergenic regions (IGRs) over 500 bp in length and analyzed expression from these regions. Seven IGRs termed bsrC, bsrD, bsrE, bsrF, bsrG, bsrH and bsrI expressed RNAs smaller than 380 nt. All small RNAs except BsrD RNA were expressed in transformed Escherichia coli cells harboring a plasmid with PCR-amplified IGRs of B. subtilis, indicating that their own promoters independently express small RNAs. Under the non-stressed condition, depletion of the genes for the small RNAs did not affect growth. Although their functions are unknown, gene expression profiles at several time points showed that most of the genes except for bsrD were expressed during the vegetative phase (4-6 h), but undetectable during the stationary phase (8 h). Mapping the 5' ends of the 6 small RNAs revealed that the genes for BsrE, BsrF, BsrG, BsrH, and BsrI RNAs are preceded by a recognition site for RNA polymerase sigma factor sigma(A). These small RNAs might lack an SD sequence and exert their actions as ncRNAs.


Introduction: Impact of nutrition on reproduction: an overview.
This Views and Reviews explores existing data regarding the impact of nutrition, supplements, and lifestyle changes as they relate to weight on the fertility of both men and women. Challenges and shortcomings in developing and performing well-designed studies of nutrition and fertility are reviewed in these five papers, and the best evidence is presented. Recommendations are made based on the data, such as they are. It appears that folic acid supplementation above the level used by women to reduce the risk of neural tube defects may be of value in producing favorable pregnancy outcomes. Certain polyunsaturated fatty acids may have a beneficial effect on fertility, and a Mediterranean diet may prove advantageous in both men and women. Data do not consistently support a beneficial effect of vitamin D on reproduction, and caffeine use has not been shown to have a deleterious effect. Alcohol use may negatively impact reproductive success, and smoking appears to have a clearly negative impact in both men and women. Present data consistently show that obesity is associated with reduced reproductive efficiency in both women and men, but the data do not confirm that weight loss proximate to attempts at conception will reverse this effect. We would do well to appreciate that the ongoing state of being obese appears to be more relevant to reproduction than changing the obese state.


Application to the alcohol dependence syndrome of a method of determining the sequential development of symptoms.
Temporal ordering of core items in the alcohol dependence syndrome was investigated in 38 men admitted to an alcoholism treatment unit. An analysis of rank sums yielded a modal sequence which resembled classical descriptions of alcoholism, though 'loss of control' appeared very early.


Role of fibrocytes and endothelial progenitor cells among low-differentiated CD34+ cells in the progression of lung sarcoidosis.
Sarcoidosis is a multisystemic granulomatous disease with still unknown etiology. Our previous studies showed a significantly higher percentage of CD34 + cells in the peripheral blood in patients with sarcoidosis (SA) compared to the control group. The objective of the present study was to characterized of the CD34 + cell population in peripheral blood in patients with SA with reference to the control group. Moreover in patients with SA, fibrocytes and endothelial cells were analysed and their relationship to the fibrosis process based on assessment of diffusing capacity for carbon monoxide (DLCO). Data from patients diagnosed with SA at Military Institute of Medicine (Warsaw, Poland) between January 2018 and December 2019 were collected and analysed ongoing basis. Peripheral blood was collected from 26 patients with newly diagnosed pulmonary SA and 16 healthy subjects. The immunomagnetic method and flow cytometry were used. Among the CD34+ progenitor cells were assessed: low-differentiated cells, hematopoietic progenitor cells and endothelial progenitor cells. The Statistica 12.0 software was used for a statistical analysis. We observed a significantly higher percentage of low-differentiated cells (13.8 vs. 2.3, P = 0.001) and endothelial cells (0.3 vs. 0.0, P = 0.001) in patients with SA compared to the control group. In the study group the median proportion of fibrocytes was 1.877% (0.983-2.340) in patients with DLCO< 80%, while in patients with DLCO> 80% was 0.795% (0.139-1.951) (P = 0.72). The median proportion of endothelial progenitor cells was higher in patients with DLCO< 80%: 0.889% (0.391-1.741), than in patients with DLCO> 80%: 0.451% (0.177-0.857) (P = 0.44). In conclusion we demonstrated for the first time the immunophenotype of peripheral CD34 + cells with the degree of their differentiation. The study confirmed the involvement of low differentiated cells and endothelial cells in patients with SA.


[Enzymatic and morphologic studies on long-term perfused dog kidneys].
21 canine and 12 human kidneys were submitted to long-term perfusion for 24 hours. During that time LDH-activity, histologic, enzyme-histochemic, and ultrastructural examinations were carried out. The findings proved that kidneys with lesser damage from ischemia showed lower activities during the first 4 to 6 hours than kidneys which were more injured before. The latter showed the same ultrastructural alterations as kidneys after perfusion for 24 hours, which suggests an irreversible partial damage of the organ.


Determination of oil-in-water using nanoemulsions as solvents and UV visible and total organic carbon detection methods.
The aim of this study was to investigate the application of oil in water (O/W) nanoemulsion as solvent in the extraction step for determination of oil content in oily water, measured using a UV visible spectrophotometer (UV-vis) and a total organic carbon (TOC) analyzer. The optical micrographs and distribution size curves showed that the use of a small amount of nanoemulsion was capable of transforming the oily water in a colloidal dispersion that can be read in the UV-vis and TOC-VCHS devices. The oil content results obtained showed great accuracy between the measurements, with very low average standard deviation (∼5%) for both UV-vis and TOC-VCHS. The new methods suggested in this work are very promising, since they allow simple, quick and accurate analyses, and especially require a lower volume of solvent (less than 1%) compared to those used in conventional analytic methods.


A case study using the beers list criteria to compare prescribing by family practitioners and geriatric specialists in a rural nursing home.
Previous studies have concluded that inappropriate medications and/or too many medications can lead to adverse events in older adults. The Beers List of potentially inappropriate medications (PIMs) for use in the elderly was developed to help guide clinicians to safely prescribe medications. Moreover, in the United States, policies exist regulating the number of prescriptions nursing home residents may take. Few studies have compared family and geriatric providers' prescribing trends. The aim of this study was to compare prescribing by family and geriatric providers in a rural U.S. nursing home using a nonequivalent 2-group analysis design with data collected via retrospective chart audits (N=92). Nursing home residents in the nongeriatric provider group had fewer total comorbidities (U=p<.001) and were less likely to have congestive heart failure (χ2=p<.001), coronary artery disease (χ2=p<.001), and degenerative joint disease (χ2=p<.001). Despite this, on average, providers who were not geriatric trained prescribed twice as many drugs per patient (U=p<.001). The odds were significantly greater of being prescribed 9 or more drugs (odds ratio 13.15, 95% confidence interval 4.3-39.5) or being prescribed at least 1 PIM (odds ratio 6.25, 95% confidence interval 1.3-29.0) if the prescriber was not geriatric trained. The prevalence in this nursing home of receiving at least 1 PIM and polypharmacy were 36.9% and 72.8%, respectively. Promethazine accounted for 46.9% of all PIMs prescribed. Geriatric education appears to have influenced prescribing patterns at this facility, with geriatric-trained providers adhering more closely to evidence-based guidelines for older patients. As geriatric educational content is incorporated into nongeriatric specialty areas, pharmacology and prescribing competencies should be an area of ongoing focus for educators.


Haemophilus influenzae can use human transferrin as a sole source for required iron.
Haemophilus influenzae grown on enriched medium containing protoporphyrin IX rather than hemin was iron starved by the addition of the chelator ethylenediamine di-o-hydroxyphenylacetic acid. Iron starvation could be overcome in each of 33 H. influenzae type b isolates by 30% Fe-saturated human transferrin but not by human lactoferrin. Among nontypeable H. influenzae, 28 of 35 isolates, including 2 of 3 systemic isolates, were able to utilize Fe-transferrin. None of 18 H. parainfluenzae isolates was able to use Fe-transferrin. Iron starvation of H. influenzae type b resulted in increased amounts of three membrane proteins of 94,000 to 98,000 daltons.


Effect of automatic image realignment on visuomotor coordination in simulated laparoscopic surgery.
During laparoscopic surgery, the surgeon's hand-eye coordination is often disrupted by the incongruent mapping between the orientation of the endoscopic view and the actual operative field. Two experiments were conducted to examine the effect of automatic image realignment on the performance of laparoscopic surgery. The first experiment investigated how visual-motor misalignment impacted laparoscopic surgery performance. Novice subjects were randomly assigned to one of the two paired viewing conditions in a simulated laparoscopic surgery environment: 1) the endoscope was either at the center of the modeled workspace with an optical axis of 90°, or at -45° from the midline of the subjects with an optical axis 45°; 2) the endoscope was either at 0°, or at 180° from the midline of the subjects, both with an optical axis of 45°. Each group of twelve subjects performed a dynamic point-and-touch task under the assigned pair of viewing conditions, each with eight image orientations, in a repeated-measures mixed design. The second experiment examined whether the automatic realigning mechanism that was activated mid-task (such that a congruent mapping between display and control was re-established if the mapping at the beginning of the task had been misaligned) was helpful to improve performance. Twelve novice subjects performed the same task as in the first experiment in a repeated-measures design. Performance was examined under three misaligned visuomotor mappings, each followed by the realigned mapping activated by the automatic realigning mechanism. Results showed that performance was best when the endoscopic image was perfectly aligned with the actual task space (0° image orientation), but degraded progressively as a function of deviation from perfect alignment. Subjects' performance maintained a consistent pattern across 8 image orientations regardless of optical axis orientation and endoscope location. Performance was improved with the automatic realigning mechanism. It is recommended that any solution to restore the visuomotor congruency in laparoscopic surgery should first align the image with the task space. This work has implications for the design of visualization systems in laparoscopic surgery.


The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause.
Targeted temperature management (TTM) is part of the standard treatment of comatose patients after out-of-hospital cardiac arrest (OHCA) to attenuate neurological injury. In other clinical settings, hypothermia promotes coagulopathy leading to an increase in bleeding and thrombosis tendency. Thus, concern has been raised as to whether TTM can be applied safely, as acute myocardial infarction requiring primary percutaneous coronary intervention (PCI) with the need of effective antiplatelet therapy is frequent following OHCA. This study investigated the influence of TTM at 33 or 36°C on various laboratory and coagulation parameters. In this single-center predefined substudy of the TTM trial, 171 patients were randomized to TTM at either 33 or 36°C in the postresuscitation phase. The two subgroups were compared regarding standard laboratory coagulation parameters, thrombelastography (TEG), bleeding, and stent thrombosis events. Platelet counts were lower in the TTM33-group compared to TTM36 (p=0.009), but neither standard coagulation nor TEG-parameters showed any difference between the groups. TEG revealed a normocoagulable state in the majority of patients, while approximately 20% of the population presented as hypercoagulable. Adverse events included 38 bleeding events, one stent thrombosis, and one reinfarction, with no significant difference between the groups. There was no evidence supporting the assumption that TTM at 33°C was associated with impaired hemostasis or increased the frequency of adverse bleeding and thrombotic events compared to TTM at 36°C. We found that TTM at either temperature can safely be applied in the postresuscitation phase after acute myocardial infarction and primary PCI.


Successful laparoscopic management of unilateral chyluria in a 5 year old.
Chyluria is defined as abnormal passage of chyle in the urine. It is usually seen in adults and is bilateral. The commonest cause is infestation with Wuchereria bancrofti. Other causes include trauma, tumours, tuberculosis and congenital malformations. This report describes the successful management of a 5-year-old child with long-standing, resistant and symptomatic unilateral chyluria. Failure of conservative treatment led to use of laparoscopic techniques to perform a lymphorenal disconnection with excellent outcome. Relevant literature is reviewed.


Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicenter prospective cohort study.
Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis (UC). Transmural activity, as defined by Milan Ultrasound Criteria (MUC) >6.2, reliably detects endoscopic activity in patients with UC. The study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy. Consecutive adult UC patients were recruited in two IBD Referral Centers and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. ROC analysis was used to compare MUC baseline values and Mayo Endoscopic Scores (MES) in predicting colectomy risk. Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (HR: 3.15, 95% CI: 1.18-8.37, p=0.02) and MUC (HR: 1.48, 95% CI: 1.19-1.76, p <0.001) were associated with colectomy risk, but only MUC was independently associated with this event at multivariable analysis (HR: 1.46, 95% CI: 1.06-2.02, p=0.02). MUC was the only independent variable associated with colectomy risk in patients with clinically active disease, OR: 1.53 (1.03-2.27) P=0.03. MUC demonstrated higher accuracy than MES (AUROC 0.83, 95% CI: 0.75-0.92 vs. 0.71 95% CI: 0.62-0.80) and better performance for predicting colectomy (p=0.02). The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7. A superior predictive value was found for transmural versus endoscopic severity for colectomy risk in UC patients.


Multiple cranial neuropathy due to varicella zoster virus reactivation without vesicular rash: a challenging diagnosis.
Ramsay Hunt syndrome is due to reactivation of varicella zoster virus (VZV) dormant in the geniculate ganglion of the facial nerve. The diagnosis is typically based on clinical triad of ipsilateral facial paralysis, otalgia, and vesicles in the auditory canal or the auricle. However, Ramsay Hunt syndrome may occur without skin eruption in up to one third of patients. Moreover, the involvement of other cranial nerves in addition to the facial nerve has been also reported. Herein, we reported a case report of a man who developed a multiple cranial neuropathy caused by VZV reactivation without skin vesicular eruption. The present case underlines a possible diagnostic challenge that clinicians may hit when facing a common disorder such as peripheral facial palsy. Indeed, clinicians must be aware that Ramsay Hunt syndrome may develop without skin vesicular eruption as well it may be complicated by multiple cranial nerve involvement. Antiviral therapy is effective in VZV reactivation for recovery of nerve function.


"Double-punch" strategy against triple-negative breast cancer via a synergistic therapy of magneto-mechanical force enhancing NIR-II hypothermal ablation.
Triple-negative breast cancer (TNBC) is a form of breast cancer that is more aggressive and harder to treat than others, with a higher probability of relapse. Its nefarious capabilities for migrating and invading other parts of the body together with the current lack of clinically established effective therapies account for a low survival rate. In this work, we demonstrate the in-tandem use of two complementary therapeutic routes to effectively combat TNBC. A versatile magnetic-photothermal converter (MPC) consisting of zinc-doped ferrite nanoparticles and polyethene glycol, is shown to display excellent therapeutic efficiency, being capable to fight TNBC via two distinct routes: magneto-mechanical force (MMF) and near-infrared-II (NIR-II) hypothermal ablation. The combined use of these two complementary and synergistic therapies, which are less aggressive to the human body compared to conventional chemotherapeutic approaches, results in the splendid suppression of TNBC migration and invasion. Remotely controlling the MPCs by an external magnetic field, results in cellular MMF effects that cause direct mechanical destruction to the cancer cell membrane, leading to its necrosis. Furthermore, the MMF disrupts intracellular lysosomes, thereby triggering the release of large amounts of protein hydrolases, which induce intracellular oxidative stress, and accelerate the induction of apoptosis. Complementing the therapeutic approach based on MMF, the excellent photothermal performance of the MPC in the NIR-II region (1064 nm) is exploited to enable effective hypothermal ablation of the tumours, which can be achieved in deep tissue layers. The proposed multifunctional nanocomposites, together with the demonstrated "double-punch" therapeutic approach, hold significant potential to pave the way for future cutting-edge weapons against the dreadful TNBC.


Whole-Genome Sequence of Brevibacillus borstelensis SDM, Isolated from a Sorghum-Adapted Microbial Community.
The isolation of novel microbes from environmental samples continues to be a key strategy for the discovery of new metabolic capacities for the degradation and transformation of lignocellulose. We report the draft genome sequence of a new strain of Brevibacillus borstelensis isolated from a sorghum-adapted microbial community derived from a compost sample.


Multidetector computed tomography coronary artery plaque predictors of stress-induced myocardial ischemia by SPECT.
Atherosclerosis imaging by multidetector computed tomography (MDCT) detects coronary artery plaque extent, distribution, location and composition. In contrast, functional imaging by single-photon emission computed tomography (SPECT) identifies perfusion defects known to predict prognosis of coronary heart disease (CHD). We sought to determine whether anatomic measures of plaque by MDCT predict functional measures of CHD by SPECT and thus, serve as measures of adverse cardiovascular prognosis. Consecutive low-to-intermediate risk symptomatic patients without known CHD (n=163) underwent both stress SPECT and MDCT. MDCT plaque extent and distribution were graded by a segment stenosis score (summation of luminal obstruction in all coronary segments) and segment involvement score (summation of segments exhibiting any plaque), respectively. Plaque location was assessed with a segments-at-risk score (plaque extent weighted by proximity) and a modified Duke CAD index. Plaque composition was graded as non-calcified, calcified and mixed. SPECT findings--summed stress (SSS), rest (SRS) and difference (SDS) scores--were compared to MDCT plaque scores. In univariate analyses, segment stenosis score (p=0.006), segments-at-risk score (p=0.002), Duke CAD index (p=0.02), and mixed plaque score (p=0.01) predicted severely abnormal SPECT. Highest compared to lowest quartile mixed plaque scores were predictive of higher SSS (8.1+/-10.3 versus 3.5+/-5.7, p<0.001), SRS (3.2+/-7.7 versus 0.9+/-3.1, p=0.008), and SDS (4.9+/-6.4 versus 2.6+/-3.9, p=0.012). In contrast, higher segment involvement scores, calcified and non-calcified plaque scores did not predict higher SPECT measures of ischemia. In multivariable analyses, comparing highest to lowest quartiles, individuals with high segment stenosis scores [odds ratio (OR) 1.97 (1.22-3.39), p=0.008], segments-at-risk scores [OR 1.71 (1.24-2.58), p=0.005], highest risk Duke CAD index category [OR 2.25 (1.12-4.41), p=0.02], and mixed plaque scores [OR 1.64 (1.10-2.43), p=0.01] had more severely abnormal SPECT scans. In low-to-intermediate risk patients without known CHD, MDCT coronary artery plaque assessment successfully identify patients at higher risk of increased extent, severity and reversibility of myocardial perfusion defects by SPECT. Anatomic MDCT findings, including plaque extent, location and composition, are independent predictors of functional ischemia and severe CHD by SPECT and thus, represent markers of adverse cardiovascular prognosis prior to the occurrence of clinical cardiovascular events.


Bilateral juvenile renal dysplasia in a Norwegian Forest Cat.
Renal dysplasia is defined as a condition of disorganised development of renal parenchyma due to abnormal differentiation. The case of a 5-month-old intact male Norwegian Forest Cat with a history of polyuria and polydipsia is reported. Ultrasonographic examination showed a slight enlargement of kidneys. Biochemical parameters, haematological examinations and clinical signs were compatible with chronic renal failure (CRF). Histological examination was correlated with a primary tubular disorganisation and modification of glomerular compartment. The clinical history together with the histological lesions is consistent with bilateral juvenile renal dysplasia in this cat. To our knowledge, feline renal dysplasia has been reported in fetal infections with panleukopenia virus; no reports indicate the idiopathic origin in feline dysplastic lesions.


Transcatheter aortic valve implantation: The road to a minimalist "stent-like" procedure.
Since the first-in-man implantation of a transcatheter aortic stented valve in April 2002 in Rouen, the procedure has expanded worldwide. In our centre, all transfemoral procedures have been performed using local anaesthesia without transoesophageal echocardiographic monitoring. To report our experience of transfemoral arterial transcatheter aortic valve implantation (TAVI) over the last 2 decades, following the evolution of devices, practices and indications. Between 2002 and 2021, 2097 consecutive patients had a TAVI procedure in our centre. Among them, 1780 underwent transfemoral arterial aortic valve implantation, and were subdivided into three groups according to the time period: before 2009; 2009-2014; and 2014-2021. Median age was 85 years, and remained unchanged over time. The mean logistic EuroSCORE gradually decreased over time (28% before 2009 vs 15% for 2009-2014 vs 11% since 2014; P<0.001). Predilatation was performed almost systematically before 2009 (93%), but was rarely performed in the last period (14%; P<0.001). Thirty-day all-cause mortality decreased over time, and was only 1.4% in 2021. Length of stay decreased considerably, with a median duration of only 2 days after the procedure, and>70% of patients were discharged home within 72hours. Similarly, procedural duration, X-ray time and contrast volume decreased over time. Transfemoral aortic valve implantation, performed as a minimalist "stent-like" procedure using only local anaesthesia, is feasible in the vast majority of patients, with excellent outcomes.


Benign lesions mimicking malignant tumors of the esophagus.
Three cases of benign lesions which mimicked malignant tumors of the esophagus are described. In all three cases, two inflammatory pseudotumors and one case of diffuse leiomyomatosis, the clinical presentations, radiologic features, and gross pathologic findings led to the mistaken diagnosis of carcinoma at thoracotomy. The benign nature of the processes was recognizable only on microscopic examination. Although most benign tumors of the esophagus are localized solitary lesions that are easily distinguished from carcinoma, occasionally benign conditions may present as infiltrative, ulcerated mass lesions. Inflammatory pseudotumor and diffuse leiomyomatosis should be included in the differential diagnosis of esophageal malignancies.


Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis.
The morphologies, intercellular organization, and cortical projection patterns of putative cholinergic neurons in the basal forebrain of the rat were examined by use of fluorescent tracer histology in combination with the pharmacohistochemical regimen for acetylcholinesterase (AChE). Intensity staining AChE-containing cells projecting to frontal sensorimotor (Area 10), parietal (Area 2), and temporal (Area 4) cortices were found ipsilaterally in nucleus preopticus magnocellularis, in nucleus basalis, and in association with the substantia innominata, the ansa lenticularis, and the lateral hypothalamic area; an essentially rostrocaudal topography was observed for these projections. AChE-containing pathways to cingulate (Area 29) and visual (Area 17) cortices derived from ipsilateral somata associated with the vertical and horizontal limbs of the diagonal band, nucleus preopticus magnocellularis, rostral portions of nucleus basalis, and the substantia innominata. Neurons innervating Area 29 were generally located more rostrally than those giving rise to AChE afferents to Area 17. The vast majority of cells appeared to innervate relatively discrete areas of the cortex. Evidence for collateralization was found only in neurons projecting to visual and cingulate cortices, and these represented only 3.2% of the cells providing AChE afferents to Areas 17 and 29. The basal forebrain AChE projection cells were typically large (greater than 25 micron in maximum cell body extent), and their somata were predominantly oval, with lesser proportions being fusiform or triangular. Many were organized in clusters, particularly in nucleus basalis.


HER2 is an important prognostic and predictive biomarker in breast cancer. Its detection makes it possible to define which patients will benefit from a targeted treatment. While assessment of HER2 status by immunohistochemistry in positive vs negative categories is well implemented and reproducible, the introduction of a new "HER2-low" category could raise some concerns about its scoring and reproducibility. We herein described the current HER2 testing methods and the application of innovative machine learning techniques to improve these determinations, as well as the main challenges and opportunities related to the implementation of digital pathology in the up-and-coming AI era.


Distance to treatment center is associated with survival in children and young adults with acute lymphoblastic leukemia.
Socioeconomic and demographic categories such as income, race, insurance status, and treatment center type are associated with outcomes in acute leukemia. This study was aimed at determining whether the distance to treatment center affects overall survival for children and young adults with acute leukemia. The National Cancer Database was queried for patients 39 years old or younger who were diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). A backward elimination procedure was used to select final multivariate Cox models. In total, 12,301 patients with AML and 22,683 patients with ALL were analyzed. The ALL model included distance to treatment center, Charlson-Deyo score, age, race, insurance status, and community income level. US census definitions of urban and rural were not statistically significant, and no interaction was significant for included variables. Compared with distances > 50 miles, all other distances were associated with improved survival (hazard ratio [HR] for ≤10 miles, 0.91; P = .04; HR for >10 to ≤20 miles, 0.86; P = .004; HR for >20 to ≤50 miles, 0.87; P = .005). The final model for AML included the same variables as the ALL model except for distance to treatment center, which was not statistically significant. For children and young adults with ALL, distances > 50 miles are associated with inferior overall survival; however, no difference is seen for AML. Although it is unknown whether differences in survival for patients with ALL based on distance are driven by relapse or treatment-related mortality, increased attention to adherence, supportive care, and logistics for patients traveling long distances is warranted. For children and young adults with acute lymphoblastic leukemia, living more than 50 miles from the treatment center is associated with worse outcomes.


[Identification of Schisandra sphenanthera and S. chinensis by random amplified polymorphic DNA sequence characterized applied region].
To establish a new method for the identification of Schisandra sphenanthera and S. chinensis. Random amplified polymorphic DNA-Sequence characterized applied region (RAPD-SCAR) method was applied to screen primers. Screening from 100 primers, only 2 random primers, which can be used to identify S. sphenanthera and S. chinensis accurately with a good reproducibility. It worked to fit them into sequence characterized applied region. RAPD-SCAR can be used to identify S. sphenanthera and S. chinensis accurately.


Antibacterial efficacy of silver diamine fluoride as a root canal irrigant.
Conventional disinfectants and medicaments have not been able to achieve and maintain sterilization of root canals. The purpose of the study was to evaluate the antibacterial efficacy of 3.8% silver diamine fluoride (SDF) in comparison with 2% chlorhexidine (CHX) against Enterococcus faecalis biofilm. Extracted human teeth were used to make 70 dentin discs that were then inoculated with E. faecalis to generate a 3-week-old biofilm model. The discs were subjected to treatment with 3.8% SDF, 2% CHX, sodium hypochlorite (NaOCl), or saline for 10 min. After exposure, the dentin discs were examined with a confocal laser scanning microscope to verify the percentage of live versus dead cells within the biofilm. Univariate one-way analysis of variance and Tukey-honestly significant difference post hoc analysis (p < .05) were performed to detect significant differences. The NaOCl group showed the greatest percentage of dead cells (62.26%) among all groups (p < .05). The SDF group showed a significantly higher percentage of dead cells (57.39%) than the 2% CHX and saline groups (p < .05). SDF possessed higher antimicrobial activity than 2% CHX against E. faecalis biofilms.


Lissencephaly: Update on diagnostics and clinical management.
Lissencephaly represents a spectrum of rare malformations of cortical development including agyria, pachygyria and subcortical band heterotopia. The progress in molecular genetics has led to identification of 31 lissencephaly-associated genes with the overall diagnostic yield over 80%. In this review, we focus on clinical and molecular diagnosis of lissencephaly and summarize the current knowledge on histopathological changes and their correlation with the MRI imaging. Additionally we provide the overview of clinical follow-up recommendations and available data on epilepsy management in patients with lissencephaly.


Molecular diagnosis of infectious diseases by nucleic acid hybridization.
Diagnostic microbiology has traditionally relied on the cultivation of an infecting agent in an in vitro system. However, the limitations of these methods have led to the development of alternative, molecular techniques which can detect specific microbial proteins or nucleic acids directly in body fluids. One such method, nucleic acid hybridization, has many attractive features including the potential for high sensitivity and specificity, the detection of a chemically stable analyte and the use of uniform reagents. Nucleic acid hybridization reactions have been used to detect a variety of microbial pathogens in assay formats using extracted nucleic acids or tissue sections. However, wider application of these techniques is limited by the fact that current methods employ radioisotopically labelled probes and cumbersome assay procedures. Solutions to these problems have been sought by the development of non-radioactive hybridization techniques which utilize enzymatic detection methods and by the development of rapid hybridization assays performed in solution. Further improvements in labelling techniques, assay formats and enzymatic detection methods should allow for the wider application of nucleic acid hybridization reactions in diagnostic microbiology.


Causal Association Between Tea Consumption and Bone Health: A Mendelian Randomization Study.
Much observational research reported that tea consumption decreases the risk of osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) which are the three major bone disorders. However, the observed correlation is inconclusive. To determine the causal relationship between genetically predicted tea intake and OA, RA, and OP, we performed a two-sample Mendelian randomization (MR) study based on large samples. The European population's genome-wide association meta-analysis (GWAS) dataset identified SNPs associated with tea consumption was obtained from Neale Lab's analysis of UK Biobank data that comprised 349,376 participants of European ancestry. We extracted genetic data for knee OA (17,885 controls and 4,462 cases), hip OA (50,898 controls and 12,625 cases), and RA (43,923 controls and 14,361 cases) from the UK Biobank and OP cases (93083 controls and 1,175 cases) from FinnGen Data Freeze 2. A MR study was conducted to examine the effect of selected single nucleotide polymorphisms (SNPs) and OA, RA, and OP risk. Several sensitivity analyses were performed with weighted median and inverse-variance weighted methods for estimating the causal effects. In this MR study, the genetically predicted per one cup increase of tea consumption was not associated with knee OA (OR 1.11,95% CI: 0.79-1.55) using IVW with random effect. Genetic predisposition to tea consumption was not associated with hip OA (OR: 1.20, 95% CI: 0.84-1.71), RA (OR: 1.24 95% CI: 0.81-1.91), and OP (OR: 1.11, 95% CI: 0.89, 1.39). Following the sensitivity analysis, there was no potential pleiotropy. According to our study, According to our study, there was no statistical power to confirm a causal relationship between tea consumption and the risk of knee OA, hip OA, RA, and OP.


Motion adaptation in chromatic motion-onset visual evoked potentials.
The aim of this study was to investigate the influence of motion adaptation on visual evoked potentials (VEPs) elicited by the onset of isoluminant chromatic motion. VEPs were recorded from the occipital cortex of human subjects using a sinusoidal grating stimulus of one cycle per degree which moved at either a velocity of 2 or 10 degrees/s and subtended a field of 7 degrees with a mean luminance of 30 cdm(-2). In the first experiment the effects of adaptation were investigated via the manipulation of the stimulus duty cycle which was varied between 11-90%. The results showed a significant (p < 0.001) reduction in the N2-P2 amplitude of the chromatic response. In contrast, P1-N2 amplitude was not significantly affected by motion adaptation. Subsequent experiments demonstrated that the chromatic motion onset VEP was attenuated not only following adaptation to isoluminant chromatic motion, but also to luminance motion as well. These results indicate that the chromatic motion onset VEP is just as susceptible as its luminance counterpart to motion after effects (MAEs) and as a result it is highly likely that it is a motion specific response. Furthermore, the fact that the VEP shows that there are cross-adaptation effects between motion defined by change in colour and by change in luminance, suggests that the two types of motion stimuli have inputs into a common motion mechanism.


Dolphin morbillivirus epizootic resurgence, Mediterranean Sea.
In July 2007, > 100 striped dolphins, Stenella coeruleoalba, were found dead along the coast of the Spanish Mediterranean. Of 10 dolphins tested, 7 were positive for a virus strain closely related to the dolphin morbillivirus that was isolated during a previous epizootic in 1990.


Hemangiopericytoma: characteristic features observed by magnetic resonance imaging and angiography.
Hemangiopericytoma is a rare vascular tumor which may originate wherever there are capillaries. We report a case of this tumor occurring in a 79-year-old Japanese man, which originated from the subcutaneous tissues of the left upper arm and reached a size of 6 x 5 x 4 cm. Histopathological and electron microscopical findings were compatible with those of benign-type hemangiopericytoma. Magnetic resonance imaging showed the most intense signal on proton density images. Angiography showed the characteristic tumor feeder artery forming a pedicle which entered the tumor and branched radially and a dense, uniform, well-demarcated, oval tumor stain. These images were helpful in performing proper operative treatment without noteworthy bleeding. These modern modalities are excellent non-invasive treatment without diagnostic procedures for the vascular tumors of soft tissues in dermatology.


Fetal Surgery for Open Spina Bifida in Canada: Initial Results.
Fetal myelomeningocele closure results in better infant outcomes than postnatal closure at the cost of potential prematurity and maternal morbidity. Our aim is to describe the setup of a fetal myelomeningocele closure program in Canada and document its outcomes. We conducted a retrospective review of all open fetal myelomeningocele closure surgeries performed at the Ontario Fetal Centre in its first 3 years of operation (2017-2020). Maternal and fetal baseline characteristics, surgical details, pregnancy outcomes, and infant follow-up until 1 year of age were recorded. Twenty-seven women underwent fetal myelomeningocele closure surgery, 10 of whom (37%) resided outside of Ontario. Mean gestational age at surgery was 25.0 ± 0.7 weeks. All surgeries were technically uncomplicated and no fetal deaths occurred. There was a significant negative correlation between increasing experience and skin-to-skin surgical time (R² = 0.36; P = 0.001). Of the 26 patients who have delivered, 4 (15.4%) experienced preterm prelabour rupture of membranes. Mean gestational age at delivery was 34.9±3.0 weeks. All but 1 patient delivered by cesarean. Maternal complications occurred in 9 women (34.6%). There were no maternal deaths, but 3 (11.5%) infant deaths. Of the 14 surviving infants who have reached at least 1 year of age, 5 (35.7%) underwent ventriculo-peritoneal shunting. Of the 9 infants who have not yet reached 1 year of age, 3 (33.3%) underwent endoscopic third ventriculostomy and none underwent shunting. Fetal open spina bifida closure can be performed in Canada, with results similar to those reported by other international expert centres. Long-term follow-up is ongoing.


Coexisting carotid stenosis in patients undergoing cardiac surgery: indications and guidelines for simultaneous operations.
The coexistence of critical carotid stenosis with coronary artery or valvular heart disease occurs in a small percentage of patients requiring open heart surgical procedures. Recognition of such combined lesions by noninvasive carotid testing identifies patients at risk for neurologic events. Our experience with 62 patients having combined simultaneous carotid and cardiac operations among 2,400 open heart surgery patients was compared with the results in 110 patients with only carotid endarterectomy operations. The outcomes indicated that carotid endarterectomy can be performed simultaneously with open heart surgical procedures with morbidity and mortality rates similar to those of isolated cervical artery operations. Thus, patients with significant coexisting carotid artery disease defined with specific criteria and coronary artery disease need not be exposed to cerebral ischemic events or to myocardial infarctions that often accompany staged operations.


Treatment with double dose of omeprazole increases β-endorphin plasma level in patients with coronary artery disease.
The proton pump inhibitor empirical trial, besides the analysis of symptoms, is the main method in the diagnosis of gastro-oesophageal reflux disease-related chest pain. β-Endorphin acts as an endogenous analgesia system. The aim of the study was verify whether β-endorphin plasma level is affected by omeprazole administration and influences the severity of anginal symptoms and outcome of the "omeprazole test" in patients with coronary artery disease (CAD) and chest pain of suspected non-cardiac origin. Omeprazole was administered to 48 patients with CAD in a randomized, placebo-controlled, crossover study design. At the beginning of the study, and again after the 14-day omeprazole and placebo treatment, the β-endorphin plasma concentration was determined. The level of plasma β-endorphin after the administration of omeprazole was significantly greater than at the start of the study and following the placebo. Responders to omeprazole had an average lower β-endorphin plasma concentration than subjects who failed to respond to this therapy. Subjects with symptoms in class III (according to the Canadian Cardiovascular Society classification) after omeprazole administration had a greater β-endorphin plasma level than subjects in class II for anginal symptom severity. Fourteen-day therapy with a double omeprazole dose significantly increases the β-endorphin plasma concentration in patients with CAD. Circulating β-endorphin does not seem to be involved in the mechanism for the "omeprazole test" outcome, although an individually different effect on pain threshold cannot be excluded.


Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targets.
Conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO). As this pathway generates numerous metabolites that are involved in various pathological conditions, IDOs and TDO represent important targets for therapeutic intervention. This pathway has especially drawn attention due to its importance in tumor resistance. Over the last decade, a large number of IDO and TDO inhibitors have been developed, many of which have entered clinical trials. Here, detailed structural comparisons of these three enzymes (with emphasis on their active sites), their involvement in cellular signaling, and their role(s) in pathological conditions are discussed. Furthermore, the most important recent inhibitors described in papers and patents and involved in clinical trials are reviewed, with a focus on both selective and multiple inhibitors. A short overview of the biochemical and cellular assays used for inhibitory potency evaluation is also presented. This review summarizes recent advances on IDO and TDO as potential drug targets, and provides the key features and perspectives for further research and development of potent inhibitors of the kynurenine pathway.


Infantile Fibrosarcoma of the Tongue Base.
Infantile fibrosarcoma is an uncommon soft tissue tumour in infants and children mostly located in the extremities. Its occurrence in the head and neck, particularly in the oral cavity is extremely rare. Here, we report a case of infantile fibrosarcoma of the tongue base in a 9-year-old boy and discuss the complexities in arriving at diagnosis and its management. The patient underwent wide local excision of the tumour. Histopathology was essential in confirming the diagnosis. As per search in English literature, this is the first case of infantile fibrosarcoma of the tongue base to be reported till date. Treatment of choice is wide local excision with or without chemotherapy.


Structural Characterization of Gallbladder Stones Using Energy Dispersive X-ray Spectroscopy and X-ray Diffraction.
Formation of the gallbladder stones is a common disease and a major health problem. The present study aimed to identify the structures of the most common types of gallbladder stones using X-ray spectroscopic techniques, which provide information about the process of stone formation. Phase and elemental compositions of pure cholesterol and mixed gallstones removed from gallbladders of patients were studied using energy-dispersive X-ray spectroscopy combined with scanning electron microscopy analysis and X-ray diffraction. The crystal structures of gallstones which coincide with standard patterns were confirmed by X-ray diffraction. Plate-like cholesterol crystals with laminar shaped and thin layered structures were clearly observed for gallstone of pure cholesterol by scanning electron microscopy; it also revealed different morphologies from mixed cholesterol stones. Elemental analysis of pure cholesterol and mixed gallstones using energy-dispersive X-ray spectroscopy confirmed the different formation processes of the different types of gallstones. The method of fast and reliable X-ray spectroscopic techniques has numerous advantages over the traditional chemical analysis and other analytical techniques. The results also revealed that the X-ray spectroscopy technique is a promising technique that can aid in understanding the pathogenesis of gallstone disease.


Harmonization of thresholds for primary skin irritation from results of human repeated insult patch tests and laboratory animal skin irritation tests.
Classification of a chemical or chemical product as a primary skin irritant using laboratory animal tests has been defined rigorously and codified in Consumer Products Safety Commission (CPSC) regulations. However, no regulatory agency, including the CPSC, has defined a primary skin irritant threshold for human repeat insult patch tests (RIPTs) that are typically conducted on products, such as cosmetics, anticipated to come into direct contact with humans. Further more, the protocols for animal and human tests are significantly different, as are the schemes for grading responses. Consequently, comparing the results of one type of test with those from the other type has proved to be difficult. In this short communication, we propose a procedure to harmonize the results from these two types of skin irritation tests and suggest that a score of "5" in animal tests, considering 24-h results on unabraded skin, is equivalent to a score of "3" in human RIPTs.


Insight into the Fe-Ni/biochar composite supported three-dimensional electro-Fenton removal of electronic industry wastewater.
For the efficient removal of the bio-refractory organic pollutants in the electronic industry wastewater, the Ni-Fe (oxides) modified three-dimension (3D) particle electrode was applied in electro-Fenton system (3D/EF), where iron ions were released from anode and deposited onto algal biochar (ABC) to prepare composite catalyst during reaction process. Firstly, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analysis were applied to confirm successful fabrication of the 3D particle electrode materials. Secondly, COD removal efficiency could reach about 80%, which was about 20% higher than that in 2D/EF system, under the optimized conditions as 2.0 g/L of Ni-ABC particle electrodes, initial pH of 3, 100 mL/min of aeration intensity and 20 mA/cm2 of applied current density. Thirdly, characterized using three-dimensional fluorescence spectroscopy and GC-MS analysis, it seemed that most of the macromolecular substances could be degraded, whereas mono-2-ethylhexyl phthalate (MEHP) was identified as the most abundant and representative compound. Finally, possible degradation pathway of MEHP in 3D/EF system was proposed including dealkylation, cleavage of C-O bond, and demethylation. Therefore, this study provides a new strategy in designing EF system employing bimetal doped biochar composite for an efficient elimination of organic pollutants within electronic industry wastewater.


IL-1 and IL-4 as reciprocal regulators of IL-2 induced lymphocyte cytotoxicity.
Interleukin 4 (IL-4) suppresses the interleukin 2 (IL-2) induced lymphokine-activated killer (LAK) cell development from human peripheral blood mononuclear cells (PBMC). Suppression is observed at high (1,000 U ml-1) as well as low (10 U ml-1) concentrations of IL-2. IL-4 needs to be present at the beginning of the IL-2 culture to exert the suppressive effect. IL-4 also inhibits the development of CD25 (Tac) antigen on the PBMC cultured in IL-2. Interleukin 1 (IL-1) can reverse the suppressive effect of IL-4 on LAK induction when added at the early phase of the IL-2 culture. IL-1 enhances IL-2 induced LAK development, which may partially explain the reversion of IL-4 inhibition by IL-1. IL-1 also reverses the inhibitory effect of IL-4 on the development of CD25 antigen expression, although IL-1 alone does not enhance the induction of CD25 expression in PBMC cultured by IL-2. Furthermore, IL-4 suppresses IL-2 induced IL-1 production in PBMC. Thus, suppression of CD25 may be a pathway for the suppression of LAK induction. The expression of CD56 is not directly associated with the expression of LAK activity. IL-4, IL-1 or combination of the two cytokines has no effect on IL-2 induced expression of CD56. These results indicate that IL-4 has an antagonistic effect and IL-1 has a synergistic effect on IL-2-induced LAK development.


Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer.
Mutations in the base excision repair gene MYH have recently been shown to confer recessive susceptibility to colorectal adenomas and carcinomas. To evaluate the contribution of germline MYH mutations to early-onset colorectal cancer, we screened a series of 358 unselected early-onset cases for germline changes in the coding sequence of the gene. Two cases harbored biallelic germline mutations (0.6%; 95% CI = 0.06-2.0) and 8 single MYH mutations (2.2%; 95% CI = 0.9-4.4). Both cases harboring biallelic MYH mutations had multiple polyps but not profuse polyposis. All cases had distally sited tumors. No biallelic mutations were detected among 354 controls. These results confirm that biallelic MYH mutations confer susceptibility to colorectal cancer but are unlikely to account for more than 3% of early-onset colorectal cancer.


Treatment of complex proximal femoral fractures with the proximal femur locking compression plate.
The PF-LCP represents a feasible alternative for the treatment of unstable inter- and subtrochanteric fractures.


K2D2: estimation of protein secondary structure from circular dichroism spectra.
Circular dichroism spectroscopy is a widely used technique to analyze the secondary structure of proteins in solution. Predictive methods use the circular dichroism spectra from proteins of known tertiary structure to assess the secondary structure contents of a protein with unknown structure given its circular dichroism spectrum. We developed K2D2, a method with an associated web server to estimate protein secondary structure from circular dichroism spectra. The method uses a self-organized map of spectra from proteins with known structure to deduce a map of protein secondary structure that is used to do the predictions. The K2D2 server is publicly accessible at http://www.ogic.ca/projects/k2d2/. It accepts as input a circular dichroism spectrum and outputs the estimated secondary structure content (alpha-helix and beta-strand) of the corresponding protein, as well as an estimated measure of error.