Binocular vision: the eyes add and subtract.
Our two eyes' views of the outside world are slightly different, providing the basis for stereopsis. A new study has found evidence that the human visual system has separately adaptable channels for adding and subtracting the neural signals from the two eyes, supporting an unconventional view of the initial stages of stereopsis.


QT intervals as an index of high serum calcium in hypercalcemia.
The relationship between QT interval and serum calcium concentration (s-Ca) was examined in 9 hypercalcemic (s-Ca greater than 11 mg/dl) patients. Three QT intervals corrected by Bazett's formula were used for the analysis: the intervals from the beginning of the QRS to the onset (QoTc), the apex (QaTc), and the end of T wave (QeTc). The measurements of s-Ca and other electrolytes were made on the blood sample taken on the same day of the electrocardiogram (ECG) recordings. The normal range of s-Ca and three QTc intervals was determined in 50 outpatients with no cardiac disease. Three QT intervals in the hypercalcemic patients were significantly shortened with a diminution in the s-Ca. The QTc intervals showed significant negative correlation with s-Ca. Sensitivity of QoTc, QaTc, and QeTc in predicting high s-Ca was 83%, 57%, and 39%, respectively, and specificity was 100%, 100%, and 89%. The PQ interval tended to be prolonged in the case of hypercalcemia, but the change was statistically insignificant. These observations suggest that QT intervals can serve as an indicator of high s-Ca and that the QoTc seems to be a good indicator of the three QTc's.


A rapid LC-MS/MS method for the quantitation of a series of benzonaphthyridine derivatives: application to in vivo pharmacokinetic and lipophilicity studies in drug development.
Drug lipophilicity is a vital physicochemical parameter that influences drug absorption, distribution, metabolism, excretion and toxicology. A comparative study of a homologous series based on a pharmaceutically active drug represents a powerful approach to the study of the effects of drug lipophilicity. We have developed a rapid and sensitive LC-MS/MS method suitable for such a homologous series and applied it to a series of DNA binding benzonaphthyridine-based antitumour drugs of differing lipophilicity. The method used a gradient elution with a run time of 7 min for simultaneous quantitation of five analogues in a pooled sample. Method validation was carried out in plasma (human and mouse) and mouse tissues (brain, heart, kidney, liver and lung). It had a limit of quantitation of 0.001 μmol/L and was linear (0.001-0.3 μmol/L) in all matrices with acceptable intra- and inter-assay precision and accuracy. This method allowed the pharmacokinetic parameters of these compounds in mice to be related to their lipophilicity as determined by their partition coefficient (LogD). Both the plasma CL (r=0.95; P=2×10⁻⁷) and V(ss) (r=0.95; P=2×10⁻⁷) exhibited a significant positive correlation with LogD values after intravenous bolus administration to mice. Consequently the plasma mean residence time for each of these five analogues decreased with increasing lipophilicity. There was also a significant positive correlation (r=0.91; P=2×10⁻⁷) between LogD values and the brain to plasma AUC ratio indicating the importance of lipophilicity in the distribution of these compounds into the brain tissue.


19q13.11 cryptic deletion: description of two new cases and indication for a role of WTIP haploinsufficiency in hypospadias.
Developmental delay/intellectual disabilities, speech disturbance, pre- and postnatal growth retardation, microcephaly, signs of ectodermal dysplasia, and genital malformations in males (hypospadias) represent the phenotypic core of the recent emerging 19q13.11 deletion syndrome. Using array-CGH for genome-wide screening we detected an interstitial deletion of chromosome band 19q13.11 in two patients exhibiting the recognizable pattern of malformations as described in other instances of this submicroscopic genomic imbalance. The deletion detected in our patients has been compared with previously reported cases leading to the refinement of the minimal overlapping region (MOR) for this microdeletion syndrome to 324 kb. This region encompasses five genes: four zinc finger (ZNF) genes belonging to the KRAB-ZNF subfamily (ZNF302, ZNF181, ZNF599, and ZNF30) and LOC400685. On the basis of our male patient 1 and on further six male cases of the literature, we also highlighted that larger 19q13.11 deletions including the Wilms tumor interacting protein (WTIP) gene, proximal to the MOR, results in hypospadias making this gene a possible candidate for this genital abnormality due to its well-known interaction with WT1. Although the mechanism underlying the phenotypic effects of copy number alterations involving KRAB-ZNF genes at 19q13.11 has not clearly been established, we suggest their haploinsufficiency as the most likely candidate for the phenotypic core of the 19q13.11 deletion syndrome. In addition, we hypothesized WTIP gene haploinsufficiency as responsible for hypospadias.


Mycobacterium avium Complex Infection as a Rare Cause of Cerebral Mass Lesion and IRIS in a Patient With AIDS: Case Report and Review of the Literature.
A patient with advanced HIV/AIDS presented with a brain abscess. While brain biopsy culture and pathology were unrevealing, universal broad-range polymerase chain reaction (uPCR) demonstrated Mycobacterium avium complex (MAC). We review the clinicopathologic characteristics of MAC brain abscesses and highlight the effectiveness of uPCR as a diagnostic tool in partially treated infections.


Genetically regulated human (T,G)-A-L specific helper T cell replacing factors possess HLA-DR and VH determinants.
Human (T,G)-A-L specific T cell helper factors secreted by in vitro activated peripheral blood lymphocytes of normal donors were characterized. Factors were passed through columns of Sepharose coupled either to antibodies against human immunoglobulin or antibodies against the variable region of the heavy (VH) and light (VL) chains of human immunoglobulin. In addition, the same factors were applied to columns of Sepharose coupled to anti-HLA-DR antibodies or to monoclonal antibodies against human Ia or beta 2-microglobulin. The activity of the antigen specific factors was removed by the anti-VH antibodies and not by anti-VL or anti-human immunoglobulin antibodies. The factors passed through Sepharose coupled to anti-DR antibodies could be removed and eluted from columns of anti-DR antibodies relevant to the donors' DR antigens. The same factors were also removed by a monoclonal antibody (anti-Ia) which recognizes a monomorphic determinant on HLA-DR, but not by monoclonal anti-beta 2-microglobulin. The results suggest that the genetically regulated (T,G)-A-L specific helper factors possess HLA-DR as well as VH determinants in their active moiety.


Health care associated infections, antimicrobial resistance and outcomes in patients admitted to intensive care unit, India: A five-Year retrospective cohort study.
The present study was conducted to study the prevalence of HAIs in a newly established MICU, common microorganisms causing HAIs and their antibiotic-sensitivity profile, and antimicrobial utilization and mortality rate. The present retrospective cohort study was carried out at AIIMS, Bhopal (2015-2019). The prevalence of HAIs was determined; sites of HAIs and common causative microorganisms were identified, and their antibiotic-sensitivity profiles were studied. The group of patients with HAIs was matched with a control group drawn from the pool of patients without HAIs; this matching was done with respect to age, gender, and clinical diagnosis. Antimicrobial utilization, Period of ICU stay, comorbidities and patient mortality rates in the two groups were analyzed. The clinical criteria by the CDC- National Nosocomial Infections Surveillance to diagnose HAIs. A total of 281 ICU patients' records were analyzed. The mean age was 47.21 ± 19.07 years. Of these 89 were found to have developed ICU-acquired HAIs (Prevalance:32%). Bloodstream infections (33%) and respiratory tract infections (30.68%), catheter-associated urinary tract infections (25.56%), and surgical site infections (6.76%) were the commonest. The most frequently isolated microorganism causing HAIs was K. pneumonia (18%), A. baumannii (14%) and E. coli (12%), 31% isolates of which were multidrug resistant. The average length of ICU stay was high in patients with HAIs (13.85 vs 8.2 days). The most common co-morbidity was type 2 diabetes mellitus (42.86%). Prolonged ICU stays [OR 1.13, (95% CI; 0.04-0.10)] and the presence of HAIs [OR 1.18(95%CI; (0.03-0.15)] were associated with an increased risk of mortality. An increased prevalence of HAIs essentially bloodstream infections and respiratory infections with MDR organisms to antimicrobials in the watch group is highly considerable. Acquisition of HAIs with MDR organisms and increased length of hospital stay are considerable risk factors for increased mortality in ICU-admitted patients. Regular antimicrobial stewardship activities and revising existing hospital infection control policies accordingly may reduce HAIs.


The quality of life of children with chronic epilepsy and their families: preliminary findings with a new assessment measure.
The aim of this study was to develop and validate a new schedule to measure the impact of epilepsy on children and their families. 30 questions assess four aspects of the child's and family's lifestyle: epilepsy and its treatment, impact on the child, impact on the parent and impact on the family. For each question, two dimensions are considered: the frequency of the problem, and its importance or degree of concern that it causes. The questionnaire was piloted on the parents of 21 children with chronic epilepsy attending a seizure clinic. Epilepsy was well controlled in half of the children and poorly controlled in the remainder. The questionnaire discriminated well between the two groups of children. Further research will be undertaken to assess the usefulness of the questionnaire on a larger and more representative group of children with epilepsy.


Cell cycle-related transformation of the E2F4-p130 repressor complex.
During G0 phase the p130, member of the pRb tumor suppressor protein family, forms a repressor complex with E2F4 which is inactivated in G1/S by hyperphosphorylation of the p130. The role of p130 after G1/S remains poorly investigated. We found that in nuclear extracts of T98G cells, the p130-E2F4-DNA (pp-E2F4) complex does not dissociate at G1/S transition, but instead reverts to the p130-E2F4-cyclin E/A-cdk2 (cyc/cdk-pp-E2F4) complex, which is detected in S and G2/M phases of the cell cycle. Hyperphosphorylation of the p130 at G1/S transition is associated with a decrease of its total amount; however, this protein is still detected during the rest of the cell cycle, and it is increasingly hyperphosphorylated in the cytosol, but continuously dephosphorylated in the nucleus. Both nuclear and cytosol cell fractions in T98G cells contain a hyperphosphorylated form of p130 in complex with E2F4 at S and G2/M cell cycle phases. In contrast to T98G cells, transformation of the p130 containing cyc/cdk-pp-E2F4 complex into the p130-pp-E2F4 repressor does not occur in HeLa cells under growth restriction conditions.


Vast assembly of vocal marine mammals from diverse species on fish spawning ground.
Observing marine mammal (MM) populations continuously in time and space over the immense ocean areas they inhabit is challenging but essential for gathering an unambiguous record of their distribution, as well as understanding their behaviour and interaction with prey species. Here we use passive ocean acoustic waveguide remote sensing (POAWRS) in an important North Atlantic feeding ground to instantaneously detect, localize and classify MM vocalizations from diverse species over an approximately 100,000 km(2) region. More than eight species of vocal MMs are found to spatially converge on fish spawning areas containing massive densely populated herring shoals at night-time and diffuse herring distributions during daytime. We find the vocal MMs divide the enormous fish prey field into species-specific foraging areas with varying degrees of spatial overlap, maintained for at least two weeks of the herring spawning period. The recorded vocalization rates are diel (24 h)-dependent for all MM species, with some significantly more vocal at night and others more vocal during the day. The four key baleen whale species of the region: fin, humpback, blue and minke have vocalization rate trends that are highly correlated to trends in fish shoaling density and to each other over the diel cycle. These results reveal the temporospatial dynamics of combined multi-species MM foraging activities in the vicinity of an extensive fish prey field that forms a massive ecological hotspot, and would be unattainable with conventional methodologies. Understanding MM behaviour and distributions is essential for management of marine ecosystems and for accessing anthropogenic impacts on these protected marine species.


Articular osteochondrosis: a comparison of naturally-occurring human and animal disease.
Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. Review. The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end-stage lesion, suggesting a shared pathogenesis across species. This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans.


Higher than normal mitochondrial DNA content associated with better outcome in acute promyelocytic leukaemia? Maybe.
Mitochondrial biology may influence the outcome of therapy for acute promyelocytic leukemia if arsenic trioxide is not part of the treatment. Inclusion of arsenic trioxide in the treatment regimen may cancel the adverse impact of certain mitochondrial abnormalities frequently associated with the disease. Commentary on: Pereira-Martins et al. Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia. Br J Haematol 2023;200:170-174.


Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy.
The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.


Review of case-mix corrected survival curves.
Survival is an end point of immense interest in cardiothoracic research. In observational studies, the comparison of survival between groups of patients is usually accomplished using a toolbox that includes Kaplan-Meier survival curves and the Cox model. The Cox model yields comparisons between groups adjusted for case-mix differences, whereas the Kaplan-Meier is a plot of survival over time without adjustment. During the past decade, new methods have emerged for case-mix adjustment of survival curves and are increasingly being used in cardiothoracic research. The purpose of this report is to describe, illustrate, and review several approaches to case-mix adjusted survival (or event-free) curves.


TMEM44 as a Novel Prognostic Marker for Kidney Renal Clear Cell Carcinoma is Associated with Tumor Invasion, Migration and Immune Infiltration.
Transmembrane (TMEM) proteins are integral membrane proteins that traverse biological membranes. Several members of the TMEM family have been linked to the development and progression of various tumors. However, the specific role and mechanism of TMEM44 in tumor biology remain largely unexplored. In this study, we initially conducted an extensive analysis using the TCGA database to investigate the expression patterns and survival associations of TMEM44 across various human tumors. Subsequently, we focused on KIRC and found a significant correlation between TMEM44 expression and this particular cancer type. To validate our findings, we performed western blot and quantitative polymerase chain reaction (qPCR) assays to confirm the expression levels of TMEM44 in KIRC. Following this, we employed a series of functional assays, including CCK8 viability assay, EDU incorporation assay, wound healing assay, and transwell migration assay, to investigate the biological role of TMEM44 in KIRC. We observed a significant upregulation of TMEM44 expression in KIRC, indicating its potential involvement in the pathogenesis of this cancer. We intervened in the expression of TMEM44 in KIRC cells and found significant inhibitory effects on cell proliferation, migration, and invasion in KIRC cells. Furthermore, our findings indicated that TMEM44 could serve as an independent prognostic factor in KIRC, highlighting its potential clinical significance. Consequently, TMEM44 holds promise as both a prognostic biomarker and a prospective therapeutic target for KIRC.


A concept analysis of women's vulnerability during pregnancy, birth and the postnatal period.
To report an analysis of the concept of vulnerability associated with pregnancy, birth and the postnatal period. The concept of vulnerability during childbirth is complex and the term, 'to be vulnerable' frequently attains a vague application. Analysis about vulnerability is needed to guide policy, practice, education and research. Clarity around the concept has the potential to improve outcomes for women. Concept analysis. Searches were conducted in CINAHL, EMBASE, PubMed, Psychinfo, MEDLINE, MIDIRS and ASSIA and limited to between January 2000 - June 2014. Data were collected over 12 months during 2014. This concept analysis drew on Morse's qualitative methods. Vulnerability during pregnancy, birth and the postnatal period can be defined by three main attributes: (a) Threat; (b) Barrier; and (c) Repair. Key attributes have the potential to influence outcome for women. Inseparable sub-attributes such as mother and baby attachment, the woman's free will and choice added a level of complexity about the concept. This concept analysis has clarified how the term vulnerability is currently understood and used in relation to pregnancy, birth and the postnatal period. Vulnerability should be viewed as a complex phenomenon rather than a singular concept. A 'vulnerability journey plan' has the potential to identify how reparative interventions may develop the woman's capacity for resilience and influence the degree of vulnerability experienced. Methodology based around complex theory should be explored in future work about vulnerability.


Experimental study on the leakage temperature field of buried CO2 pipelines.
The leakage of small holes in the buried CO2 pipeline is not easy to detect, which leads to the problem of the inability to accurately trace the source of the pipeline repair in the later stage. This paper designs and builds an experimental system to simulate the leakage of buried CO2 pipelines and conducts experiments on the leakage of small holes in buried CO2 pipelines to investigate the changes in the surrounding soil temperature when they leak. The results showed that the type of movement of CO2 in porous media after it is released from the leak is "funneling." At a distance of about 50 mm from the horizontal, the temperature difference in the horizontal surface is smallest at the 50 cm closest to the vertical distance of the leak, while at a distance of 225 mm from the horizontal, the temperature difference in the horizontal surface is largest at the 70 cm farthest from the vertical distance of the leak. The research results can provide a theoretical basis for the later development of technologies that can quickly locate the leakage points of buried CO2 pipelines and accurately determine their leakage status.


Genomic Analysis of Bacteriocin-Producing Staphylococci: High Prevalence of Lanthipeptides and the Micrococcin P1 Biosynthetic Gene Clusters.
Bacteriocins are antimicrobial peptides produced by bacteria. This study aimed to in silico analyze the presence of bacteriocin gene clusters (BGCs) among the genomes of 22 commensal Staphylococcus isolates from different origins (environment/human/food/pet/wild animals) previously identified as bacteriocin producers. The resistome and plasmidome were studied in all isolates. Five types of BGC were detected in 18 genomes of the 22 bacteriocin-producing staphylococci included in this study: class I (Lanthipeptides), class II, circular bacteriocins, the non-ribosomal-peptide lugdunin and the thiopeptide micrococcin P1 (MP1). A high frequency of lanthipeptides was detected in this collection: BGC variants of BSA, bacCH91, and epilancin15X were identified in two Staphylococcus aureus and one Staphylococcus warneri isolates from food and wild animals. Moreover, two potentially new lanthipeptide-like BGCs with no identity to database entries were found in Staphylococcus epidermidis and Staphylococcus simulans from food and wild animal, respectively. Interestingly, four isolates (one S. aureus and one Staphylococcus hominis, environmental origin; two Staphylococcus sciuri, food) carried the MP1 BGC with differences to those previously described. On the other hand, seven of the 22 genomes (~32%) lacked known genes related with antibiotic or disinfectant-acquired resistance mechanisms. Moreover, the potential carriage of plasmids was evaluated, and several Rep-proteins were identified (~73% of strains). In conclusion, a wide variety of BGCs has been observed among the 22 genomes, and an interesting relationship between related Staphylococcus species and the type of bacteriocin has been revealed. Therefore, bacteriocin-producing Staphylococcus and especially coagulase-negative staphylococci (CoNS) can be considered good candidates as a source of novel bacteriocins.


Decreased expression of femXAB genes and fnbp mediated biofilm pathways in OS-MRSA clinical isolates.
Methicillin-Resistant Staphylococcus aureus (MRSA) is a significant threat to human health. Additionally, biofilm forming bacteria becomes more tolerant to antibiotics and act as bacterial reservoir leading to chronic infection. In this study, we characterised the antibiotic susceptibility, biofilm production and sequence types (ST) of 74 randomly selected clinical isolates of S. aureus causing ocular infections. Antibiotic susceptibility revealed 74% of the isolates as resistant against one or two antibiotics, followed by 16% multidrug-resistant isolates (MDR), and 10% sensitive. The isolates were characterized as MRSA (n = 15), Methicillin-sensitive S. aureus (MSSA, n = 48) and oxacillin susceptible mecA positive S. aureus (OS-MRSA, n = 11) based on oxacillin susceptibility, mecA gene PCR and PBP2a agglutination test. All OS-MRSA would have been misclassified as MSSA on the basis of susceptibility test. Therefore, both phenotypic and genotypic tests should be included to prevent strain misrepresentation. In addition, in-depth studies for understanding the emerging OS-MRSA phenotype is required. The role of fem XAB gene family has been earlier reported in OS-MRSA phenotype. Sequence analysis of the fem XAB genes revealed mutations in fem × (K3R, H11N, N18H and I51V) and fem B (L410F) genes. The fem XAB genes were also found down-regulated in OS-MRSA isolates in comparison to MRSA. In OS-MRSA isolates, biofilm formation is regulated by fibronectin binding proteins A & B. Molecular typing of the isolates revealed genetic diversity. All the isolates produced biofilm, however, MRSA isolates with strong biofilm phenotype represent a worrisome situation and may even result in treatment failure.


Outcomes of patients with gynecologic malignancies undergoing video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion.
We evaluated the indications and outcomes of patients with known gynecologic malignancies that underwent video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion. After IRB approval was obtained, a retrospective study of patients with gynecologic malignancies who underwent planned VATS/pleurodesis between 1/2000 and 7/2010 was performed. Abstracted data included demographics, diagnosis, disease status, treatment history, indication for VATS, complications, and outcomes. Forty-two patients with a gynecologic malignancy underwent VATS/pleurodesis. Median age was 63 years. Twenty-nine patients (69%) had ovarian cancer. Fifty-seven percent had recurrent disease at the time of VATS and 57% were undergoing chemotherapy at the time of VATS. Eight patients (19%) underwent perioperative VATS to improve pulmonary status. Seven patients (17%) underwent a palliative VATS. The median length of stay was 7 days (range 1-53). Sixty-two percent had gross disease noted at the time of VATS. A mean of 1650 cc of fluid was drained at time of surgery (range 300-4500), and the majority (88%) of patients had a talc pleurodesis performed. Seven patients (17%) were readmitted within 30 days; 6 were for complications unrelated to their VATS. One patient was readmitted with hospital-acquired pneumonia and died during readmission. Median time to death after VATS was 104 days (range 4-1062). Patients who underwent a perioperative VATS had the longest survival (845 days). Patients with gynecologic malignancies may require a VATS/pleurodesis for symptomatic pleural effusions. This procedure appears to be safe and effective in this patient population.


Clinical epidemiology and outcomes of peripheral venous catheter-related bloodstream infections at a university-affiliated hospital.
Despite enormous clinical experience of using peripheral vascular catheters, there is still controversy over the incidence and clinical relevance of bloodstream infections caused by these devices and the measures for preventing them. We performed a prospective study to determine the clinical epidemiology and outcomes of nosocomial bloodstream infections caused by short- and mid-line peripheral venous catheters among a group of non-intensive care unit patients. Cases of peripheral venous catheter-related bloodstream infections (PVC-BSIs) were compared to cases of central venous catheter-related bloodstream infections (CVC-BSIs). From October 2001 to March 2003, 150 cases of vascular catheter-related bloodstream infections were identified among 147 patients. Seventy-seven episodes (0.19 cases/1000 patient-days) were PVC-BSIs and 73 episodes (0.18 cases/1000 patient-days) were CVC-BSIs. Compared with CVC-BSIs, patients with PVC-BSIs more often had the catheter inserted in the emergency department (0 vs 42%), had a shorter duration from catheter insertion to bacteraemia (mean: 15.4 vs 4.9 days) and had Staphylococcus aureus (33 vs 53%) more frequently as the causative pathogen. Among patients with PVC-BSIs, catheters inserted in the emergency department had a significantly shorter duration in situ compared with those inserted on hospital wards (mean: 3.7 vs 5.7 days). Patients with PVC-BSIs caused by S. aureus had a higher rate of complicated bacteraemia (7%) and higher overall mortality (27%) than patients with PVC-BSIs caused by other pathogens (0 and 11%, respectively). Bloodstream infections remain underestimated and potentially serious complications of peripheral vascular catheterisation. Targeted interventions should be introduced to minimise this complication.


Mechanistic differences among retaining disaccharide phosphorylases: insights from kinetic analysis of active site mutants of sucrose phosphorylase and alpha,alpha-trehalose phosphorylase.
Sucrose phosphorylase utilizes a glycoside hydrolase-like double displacement mechanism to convert its disaccharide substrate and phosphate into alpha-d-glucose 1-phosphate and fructose. Site-directed mutagenesis was employed to characterize the proposed roles of Asp(196) and Glu(237) as catalytic nucleophile and acid-base, respectively, in the reaction of sucrose phosphorylase from Leuconostoc mesenteroides. The side chain of Asp(295) is suggested to facilitate the catalytic steps of glucosylation and deglucosylation of Asp(196) through a strong hydrogen bond (23 kJ/mol) with the 2-hydroxyl of the glucosyl oxocarbenium ion-like species believed to be formed in the transition states flanking the beta-glucosyl enzyme intermediate. An assortment of biochemical techniques used to examine the mechanism of alpha-retaining glucosyl transfer by Schizophyllum commune alpha,alpha-trehalose phosphorylase failed to provide evidence in support of a similar two-step catalytic reaction via a covalent intermediate. Mutagenesis studies suggested a putative active-site structure for this trehalose phosphorylase that is typical of retaining glycosyltransferases of fold family GT-B and markedly different from that of sucrose phosphorylase. While ambiguity remains regarding the chemical mechanism by which the trehalose phosphorylase functions, the two disaccharide phosphorylases have evolved strikingly different reaction coordinates to achieve catalytic efficiency and stereochemical control in their highly analogous substrate transformations.


The novel Next Step test is a reliable measure of anticipatory postural adjustments made by children with cerebral palsy prior to taking a step.
Children with cerebral palsy (CP) make smaller medio-lateral anticipatory postural adjustments (APAs) than typically developing peers when stepping forward to a medial target. They are also less accurate at reaching the stepping target. The Next Step test involves the biomechanical measurement of APAs and foot placement error. These may be useful outcome measures to evaluate dynamic balance in a clinical trial. The reliability of the measures must be assessed to establish their reliability as research tools. What is the inter-rater and intra-rater reliability of stepping accuracy and measures of APAs made by children prior to taking a step? Typically developing (TD) (n = 14) or children with CP (n = 16) were recruited from local clinics. Children stepped to electro-luminescent targets placed medially and laterally to each foot. Stepping responses were measured using a force plate and 3D motion analysis of markers placed on the feet and pelvis. The APA was defined as the movement of the centre of pressure (COP) and the centre of mass (COM) estimated via pelvic markers, prior to lifting the lead leg. Stepping accuracy was defined as the absolute distance between the target and end foot position. Participants undertook two data collection sessions separated by at least one week. In session one, the test was measured by rater 1 who repeated this in session two, along with another data collection by a rater 2 or rater 3, after a rest period. Where data were normally distributed, they were assessed for inter-rater and intra-rater reliability using an intra-class correlation coefficient (ICC) and Bland-Altman plots. The standard error of measurement was calculated to determine the minimum difference needed to detect true change. There was no between-group differences in group characteristics (age, weight, height) or in stepping velocity. We found good to excellent reliability when measuring the amplitude and velocity of medio-lateral APAs (ICC range 0.73-0.89). The reliability of antero-posterior APAs was more variable (ICC range 0.08-0.92). The minimum difference to detect a true change for peak medio-lateral motion of COP ranges from 23.7 mm to 29.6 mm and for peak velocity of medio-lateral COM estimate 41-61.9 mm. Stepping accuracy was not normally distributed. The Next Step test is a reliable measure of dynamic balance. The peak medio-lateral motion of the COP and medio-lateral velocity of the COM estimate are reliable when measured during a constrained stepping task in ambulant children with cerebral palsy.


Frequency of GBA variants in autopsy-proven multiple system atrophy.
Multiple system atrophy (MSA) is marked by abnormal inclusions of alpha-synuclein in oligodendrogliocytes. Etiology remains unknown. Variants in the glucocerebrosidase gene have been associated with other synucleinopathies, dementia with Lewy bodies and Parkinson disease. It is unclear whether glucocerebrosidase variants are associated with MSA. To analyze the frequency of glucocerebrosidase gene variants among autopsy-proven cases of MSA at a brain bank in New York City. The glucocerebrosidase gene was fully sequenced in the 17 autopsy-proven MSA cases with extractable DNA at the Columbia University New York Brain Bank from 2002 to 2016. To test if the MSA cases in the brain bank are enriched for GBA variants, we compared the GBA variant frequency in MSA to all brain bank cases with pure Alzheimer's disease (AD) at Columbia University for whom GBA genotype was available (n=82). 4/17 (23.5%) MSA cases carried glucocerebrosidase gene variants, including an individual homozygous for N370S, and one each who were heterozygous carriers of N370S, T369M and R496H. Among the comparator cases with pure AD, 3 of the 82 autopsies (3.7%) carried GBA variants (P = 0.0127, Fisher exact test), including one case each of N370S homozygote, and R496H and T369M heterozygous variant. We found a higher frequency of glucocerebrosidase variants among pathologically diagnosed MSA cases in our brain bank compared to AD autopsies. This study demonstrates the need for further investigation into the role of glucocerebrosidase and lysosomal dysfunction in the etiology of MSA.


Neonatal administration of vasopressin antiserum induces long-term deficits on active and passive avoidance behaviour in rats.
Two-day-old male rats received a subcutaneous injection of arginine-vasopressin (AVP) antiserum and avoidance behaviour was studied 3 months later. Rats treated with the antiserum showed a clear retention deficit in a one-trial learning, step-through passive avoidance situation. Anti-AVP treatment also induced an impairment on the acquisition of a two-way active avoidance task. Systolic blood pressure was lower than normal in these animals. The results obtained appear to be indicative of the high vulnerability of the developing nervous system, and are discussed in the context of the different hypothesis on the role of central or peripheral mechanisms in the behavioural effects of AVP. Although no definite conclusions may be drawn in this regard, the present data strongly suggest that neonatal administration of AVP antiserum exerts long-lasting effects upon the functionality of several physiological mechanisms related to the behavioural adaptation of the organism.


Identification and characterization of genes differentially expressed in the resistance reaction in wheat infected with Tilletia tritici, the common bunt pathogen.
The differentially virulent race T1 of common bunt (Tilletia tritici) was used to inoculate the wheat lines Neepawa (compatible) and its sib BW553 (incompatible) that are nearly isogenic for the Bt-10 resistance gene. Inoculated crown tissues were used to construct a suppression subtractive hybridization (SSH) cDNA library. Of the 1920 clones arrayed from the SSH cDNA library, approximately 10 % were differentially regulated. A total of 168 differentially up-regulated and 25 downregulated genes were identified and sequenced; 71 % sequences had significant homology to genes of known function, of which 59 % appeared to have roles in cellular metabolism and development, 24 % in abiotic/biotic stress responses, 3 % involved in transcription and signal transduction responses. Two putative resistance genes and a transcription factor were identified among the upregulated sequences. The expression of several candidate genes including a lipase, two non-specific lipid transfer proteins (ns-LTPs), and several wheat pathogenesis-related (PR)-proteins, was evaluated following 4 to 32 days postinoculation in compatible and incompatible interactions. Results confirmed the higher overall expression of these genes in resistant BW553 compared to susceptible Neepawa, and the differential up-regulation of wheat lipase, chitinase and PR-1 proteins in the expression of the incompatible interaction.


Case report: cystic partially differentiated nephroblastoma (Wilms tumor).
A case of a cystic partially differentiated nephroblastoma treated with combined chemotherapy after removal in a 2-month old newborn is reported. Cystic partially differentiated nephroblastoma is a newly described clinicopathologic entity, involving elements of a nephroblastoma and cystic disease, and it is believed to be a pathologic derivative of the metanephric blastema and not related to renal dysplasia. Cystic partially differentiated nephroblastoma is distinguished from multilocular cysts of the kidney by the presence of partially differentiated renal elements in the septa of cysts. The aggressive appearance of the cells led to the treatment of this tumor as potentially malignant.


Alkyl and carboxylalkyl esters of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxic, and antitumor activity.
Esters of 4'-demethyl-4-deoxypodophyllotoxin (DDPT) with alkanoic acids and alkanedioic acids were prepared and tested for cytotoxic and antitumor activity. Among 19 esters, esters of propanoic acid, tetradecanedioic acid, 13-carboxyundecanoic acid, and hexadecanedioic acid improved the antitumor activity compared with that of the starting compounds, DDPT.


Understanding chemistry: from "heuristic (soft) explanations and reasoning by analogy" to "quantum chemistry".
"Soft theories," i.e., "heuristic models based on reasoning by analogy" largely drove chemistry understanding for 150 years or more. But soft theories have their limitations and with the expansion of chemistry in the mid-20th century, more and more inexplicable (by soft theory) experimental results were being obtained. In the past 50 years, quantum chemistry, most often in the guise of applied theoretical chemistry including computational chemistry, has provided (a) the underlying "hard evidence" for many soft theories and (b) the explanations for chemical phenomena that were unavailable by soft theories. In this publication, we define "hard theories" as "theories derived from quantum chemistry." Both soft and hard theories can be qualitative and quantitative, and the "Houk quadrant" is proposed as a helpful categorization tool. Furthermore, the language of soft theories is often used appropriately to describe quantum chemical results. A valid and useful way of doing science is the appropriate use and application of both soft and hard theories along with the best nomenclature available for successful communication of results and ideas.


Children with early refusal to eat: follow-up in adolescence.
To describe the adolescent outcome of infant refusal to eat (RTE) and to investigate early predictors of adolescent outcomes. 19 of 25 children with RTE and 35 of 42 controls were assessed at age 16. The participants rated eating attitudes and self-perceptions with a Swedish version of the Children's Eating Attitudes Test (ChEAT) and a Swedish self-perception measure. Weight and height were assessed through self-reports, and body mass index (BMI) was computed. Child and family variables measured from infancy through age 4 were used as predictors. RTE and controls did not differ with regard to disturbed eating attitudes, BMI or self-perceptions. There were no relations between early predictors and adolescent disturbed eating for the whole sample, but breastfeeding problems and social adversity in the early years predicted negative self-perceptions, and weight at 4 y predicted adolescent BMI. For the RTE group, low birthweight predicted higher levels of disturbed eating attitudes and less positive self-perceptions. For the control group, social adversity predicted high BMI. RTE does not seem to constitute a risk factor for adolescent disturbed eating. Further, there may be different risk factors for adolescent disturbed eating for children with and without RTE.


Effect of Crosslinking Agent Concentration on the Properties of Unmedicated Hydrogels.
Novel polyethylene oxide (PEO) hydrogel films were synthesized via UV crosslinking with varying concentrations of pentaerythritol tetra-acrylate (PETRA) as crosslinking agent. The aim was to study the effects of the crosslinking agent on the material properties of hydrogel films intended for dermatological applications. Fabricated film samples were characterized using swelling studies, scanning electron microscopy, tensile testing and rheometry. Films showed rapid swelling and high elasticity. The increase of PETRA concentration resulted in significant increase in the gel fraction and crosslinking density (ρc), while causing a significant decrease in the equilibrium water content (EWC), average molecular weight between crosslinks (\({\overline{M}}_{c}\)), and mesh size (ζ) of films. From the scanning electron microscopy, cross-linked PEO hydrogel network appeared as cross-linked mesh-like structure with interconnected micropores. Rheological studies showed PEO films required a minimum of 2.5% w/w PETRA to form stable viscoelastic solid gels. Preliminary studies concluded that a minimum of 2.5% w/w PETRA is required to yield films with desirable properties for skin application.


Isolation of human cardiac troponin T and localization of epitopes recognized by monoclonal antibodies to cardiac troponin T.
Human cardiac troponin T has been isolated and its properties compared with those of rabbit skeletal and bovine cardiac troponin T. Seven monoclonal antibodies to troponin T have been obtained. Two antibodies cross-reacted with both cardiac and skeletal troponin T and recognized epitopes located between residues 98-177 of bovine cardiac troponin T. Five other antibodies were specific for cardiac troponin T and recognized antigenic determinants located between residues 180-258 of bovine cardiac troponin T. Localization of antigenic determinants in the central part of troponin T seems to be due to the high hydrophilicity and flexibility of this part of the molecule. The monoclonal antibodies thus obtained may be used for diagnosing various types of human heart diseases.


Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site, 2: relevance of an N-terminal helix.
Proteolytic activation of the HIV-1 envelope glycoprotein gp160 is selectively performed by the proprotein convertase furin at the C-terminus of the sequence R508-E-K-R511 (site 1), in spite of the presence of another consensus sequence, Lys500-Ala-Lys-Arg503 (site 2). On the basis of the solution structural analysis of the synthetic peptide p498, spanning the gp160 sequence Pro498-Gly516, we previously suggested a possible role of an N-terminal helix in regulating the exposure and accessibility of the gp160 physiological cleavage site, enclosed in a loop. Here we report on the activity and conformation of the 23-residue peptide h-REKR, designed to exhibit a large N-terminal helix, followed by the gp160 native sequence, Arg508-Gly516. h-REKR is digested by furin with high efficiency, comparable to the full native p498. Circular dichroism analyses, in mixtures from pure water to 98 % trifluoroethanol, outline a significant content of helical structure in the peptide conformation. The molecular model obtained from NMR data collected in trifluoroethanol/water, by means of DYANA and AMBER simulations, indeed has helical structure on a large N-terminal segment. Such a long helix does not seem to affect the loop conformation of the C-terminal site 1-containing sequence, which exhibits the same proton chemical shifts already observed for the full native p498.


Corrigendum to "Dracohodin Perochlorate Stimulates Fibroblast Proliferation via EGFR Activation and Downstream ERK/CREB and PI3K/Akt/mTOR Pathways In Vitro".
[This corrects the article DOI: 10.1155/2019/6027186.].


Thermodynamics of the interaction of epsilon-dinitrophenyl-L-lysine and the subunits (Fab) of bovine colostral immunoglobulin G1 anti-dinitrophenyl antibody.
Investigation of the binding of epsilon-DNP-1-lysine to the subunits (Fab') of bovine colostral IgG1 anti-DNP over a wide range of temperatures yielded non-linear van't Hoff plots with curvatures which were indicative of large positive heat capacity changes. Thermodynamic functions which were calculated using a non-linear least-squares procedure revealed an enthalpy-entropy compensation mechanism for binding. While the enthalpy factor was the driving force for the hapten-subunit interaction(s) at low temperatures, the entropy factor assumed greater importance with increasing temperatures. In addition, the enthalpy-entropy compensation plot for the interaction of epsilon-DNP-1-lysine with bovine colostral Fab' anti-DNP, intact anti-DNP IgG1 and rabbit IgG anti-DNP revealed a constant compensation temperature (T degrees c) of 27 degrees which might be considered as indicative of a single kind of protein-solvent conformation.


Functionalized amphipols: a versatile toolbox suitable for applications of membrane proteins in synthetic biology.
Amphipols are amphipathic polymers that stabilize membrane proteins isolated from their native membrane. They have been functionalized with various chemical groups in the past years for protein labeling and protein immobilization. This large toolbox of functionalized amphipols combined with their interesting physico-chemical properties give opportunities to selectively add multiple functionalities to membrane proteins and to tune them according to the needs. This unique combination of properties makes them one of the most versatile strategies available today for exploiting membrane proteins onto surfaces for various applications in synthetic biology. This review summarizes the properties of functionalized amphipols suitable for synthetic biology approaches.


Semiconductor probe measurements in beagle pups during deciduous tooth development.
Bone-seeking radiopharmaceuticals were used together with clinical and radiographic procedures to study tooth development in dogs. Similarities in the pattern and time course of radiopharmaceutical uptake in jaw areas studied suggest that changes in alveolar bone metabolism are not closely related to eruption times of individual teeth.


Orthograde axonal and transcellular transport of different fluorescent tracers in the primary visual system of the rat.
The differential labeling properties of various fluorescent tracers injected intraocularly were investigated using as a model the rat primary visual system. All of the tracers tested (Fast Blue, FB; True Blue, TB; Nuclear Yellow, NY; bisbenzimide, BB; Evans Blue, EB; propidium iodide, PI) produced a retrograde neuronal labeling of oculomotor neurons. However, no such labeling was observed in the medial pretectal nucleus (NPM) considered to be the site of origin of the rat centrifugal visual pathway. Orthograde transport within the axons of the optic tract and their terminal arborizations were visualized directly with FB and TB. No evidence of EB or PI orthograde transport was demonstrated. Furthermore, FB, TB, NY and BB displayed varying degrees of leakage from the optic axons and terminals into the extracellular space, there to be taken up by glial (FB, TB, NY, BB) and neuronal (NY, BB) somas of the primary optic system or in adjacent structures including NPM (BB). The neuronal labeling with NY or BB does not result from the retrograde axonal transport but appears to involve an orthograde transneuronal process transport. Some limitations in the use of different fluorescent tracers for determining neuronal connections are discussed.


Influence of ketanserin (serotonin antagonist) on bladder and urethral function.
As it is known that serotonin or 5-hydroxytryptamine can enhance bladder activity, we studied urodynamically the effect of ketanserin, a serotonin antagonist, in 17 patients, in the hope that this drug might be useful in treating unstable bladders. However, a relaxant effect on bladder contractility could not be demonstrated. On the contrary, a significant decrease of the urethral pressure was observed, suggesting that ketanserin might still have a possible role in promotion of bladder emptying. The relaxant effect on the urethra suggests some alpha-sympathicolytic activity of ketanserin.


Quantification of ultraviolet protective effects of pityriacitrin in humans.
Pityriacitrin (PIT), produced by Malassezia yeasts, is an UV absorbing substance that might cause hypopigmentation in pityriasis versicolor alba. We aimed to investigate the UV protective effect of PIT in humans using in vitro and in vivo test methods. Spectrophotometry of PIT cream and the vehicle was performed in the wavelength range from 290 to 400 nm. UV transmission and the sun protection factor (SPF) were assessed for different cream formulations. Using colorimetry we evaluated erythema and pigmentation following irradiation of cream-protected and non-protected skin of healthy subjects. UVB as well as UVA transmission decreased with increasing PIT concentrations. An increase of PIT concentration of 1.25, 2.5, and 5% was associated with slightly increasing SPFs of 1.4, 1.5, and 1.7, respectively. Our in vivo tests confirmed the validity of the SPF of PIT 5% cream determined in vitro. In conclusion, the UV protective effect of PIT is all in all very weak suggesting that PIT is likely only an inferior cofactor in the development of hypopigmentation in pityriasis versicolor alba lesions following sun exposure.


Resolution by graphical methods of the equations for allosteric competitive inhibition and activation in Michaelian enzyme and transport systems. Application to the competitive inhibition of glucose transport in brain by phlorizin and phloretin.
A brief exposition of the theory of competition in systems conforming to simple Michaelis-Menten kinetics is given. Emphasis is placed on an operational distinction between: 10 True competition between substrate and inhibitor for a single, common binding site: fully competitive inhibition, type IA. 20 False competition between S and I for two separate sites that are associated allosterically: pseudocompetitive inhibition, type Ib. 30 A simple graphical test is presented that differentiates between the two types of inhibitor and permits calculation of the four dissociation constants governing the partial reactions of a two-site allosteric model. This test is equally applicable to certain cases of activation: affinity-type activation, type Ib. 40 The usefulness of the proposed test is illustrated using data from the literature, dealing with the effect of phlorizin and phloretin on the D-glucose transport system in brain.


Activation of heterotrimeric G-proteins independent of a G-protein coupled receptor and the implications for signal processing.
Heterotrimeric G-proteins are key transducers for signal transfer from outside the cell, mediating signals emanating from cell-surface G-protein coupled receptors (GPCR). Many, if not all, subtypes of heterotrimeric G-proteins are also regulated by accessory proteins that influence guanine nucleotide binding, guanosine triphosphate (GTP) hydrolysis, or subunit interactions. One subgroup of such accessory proteins (activators of G-protein signaling; AGS proteins) refer to a functionally defined group of proteins that activate selected G-protein signaring systems in the absence of classical G-protein coupled receptors. AGS and related proteins provide unexpected insights into the regulation of the G-protein activation-deactivation cycle. Different AGS proteins function as guanine nucleotide exchange factors or guanine nucleotide dissociation inhibitors and may also influence subunit interactions by interaction with GBgamma. These proteins play important roles in the generation or positioning of signaling complexes and of the regulation of GPCR signaling, and as alternative binding partners for G-protein subunits. Perhaps of even broader impact is the discovery that AGS proteins provide a foundation for the concept that heterotrimeric G-protein subunits are processing signals within the cell involving intrinsic cues that do not involve the classical signal input from a cell surface GPCR.


Surgical plating versus closed reduction for fractures in the distal radius in older patients: a cost-effectiveness analysis from the hospital perspective.
Given the cost differential between surgical and non-surgical management of distal radius fractures, we aimed to evaluate the cost-effectiveness of surgical compared with non-surgical treatment of distal radius fractures in a cohort of older patients. This evaluation was conducted alongside the combined randomized and observational study of surgery for fractures of the distal radius in the elderly (CROSSFIRE) trial (ACTRN 12616000969460) which compared surgical (open reduction and internal fixation using volar-locking plate (VLP) fixation) and non-surgical (closed fracture reduction and cast immobilization (CR)) treatment for displaced distal radius fractures in patients ≥60 years. Cost-effectiveness was assessed from the perspective of the public hospital funder. Hospital records from a sub-sample of participants were used to estimate costs. Outcomes were patient-reported wrist pain and function questionnaire (PRWE) scores and quality adjusted life years (QALYs) calculated using the EuroQoL five-dimension five-level tool (EQ-5D-5L). From 166 participants (81 surgical, 85 non-surgical), costs were obtained for 56 (29 surgical, 27 non-surgical). The mean costs for VLP fixation were Australian dollars (AUD) 6668 (95% CI $4857 to $8479) compared to AUD 3343 (95% CI $1304 to $5381) for CR. The incremental cost-effectiveness ratios (ICER) to achieve a 1-point improvement in the PRWE were AUD 375, AUD 1736 and AUD 1126 at 3, 12 and 24 months for VLP compared with CR. At 12 months, the cost effectiveness was dominated by CR (lower cost and better QoL) whereas at 24 months, the incremental cost per QALY gained by VLP was AUD 1 946 127. In the treatment of distal radius fractures in patients ≥60 years, VLP fixation was not cost-effective compared with CR from the perspective of hospital funders.


Abdominal aortic aneurysm in association with a congenital pelvic horseshoe kidney: sentinel report and technical consideration.
A case of an abdominal aortic aneurysm in the presence of a congenital pelvic horseshoe kidney is described and the technical approach discussed. Renal function was preserved by 'double clamping' during the proximal anastomosis and infusing cold crystalloid into cannulated renal arteries originating from the aneurysm sac.


Professional indemnity insurance: a looming crisis.
Dentists around the world have watched with alarm and concern the development of the problems with professional indemnity insurance in the United States. Premiums for general practitioners start at about US$ 4000, with at-risk specialists such as oral surgeons or orthodontists in California paying upwards of $ 30,000. Some Californians have signs in their waiting rooms saying 'I am not insured!'


Neural bases of falsification in conditional proposition testing: evidence from an fMRI study.
The ability of testing the validity of a conditional statement is important in our everyday life. However, the brain mechanisms underlying this process, especially falsification process which is important in daily life, but especially crucial to scientific reasoning and research is not as yet completely clear. Therefore, in the present study, we used event-related functional magnetic resonance imaging (fMRI) to examine the neural bases of the falsification process in testing the validity of a conditional statement as used in Wason's (1966) selection task. Our fMRI results showed that: (1) compared with the baseline condition, both Falsification (by using Modus Ponens, and Modus Tollens) and Non-Falsification conditions (affirming the consequent, and denying the antecedent) activated the left frontal areas (BA44/45, or BA6), and basal ganglia, the areas previously found in the rule-guided conditional reasoning operations; the parietal area (BA40, BA7) for recruiting cognitive resources to represent and maintain the different evidential information in working memory. (2) The left middle frontal gyrus (BA9) and cerebellum were shown to be activated in the contrast of Falsification condition versus Non-Falsification condition and in the contrast of MT versus Non-Falsification condition. These results indicated that the left middle frontal gyrus (BA9) might be the key brain region involved in the falsification process of conditional statement for which abstracting and integrating logical relationships, and inhibiting the distraction of the irrelevant information were the essential processes. Moreover, the cerebellum was found to be responsible for constructing an internal working model. In addition, our brain imaging results might support the dual-process theory of reasoning.


Cytokine production by human colonic intraepithelial lymphocytes in controls and ulcerative colitis.
Using an ELISA technique, concentrations of gamma-interferon and interleukin-2 were assayed in the supernatants of colonic intraepithelial lymphocytes cultured with or without phytohaemagglutinin (PHA). IntraepitheHal lymphocytes produced low concentrations of gamma-interferon and interleukin-2 when stimulated with PHA, but significantly more than when unstimulated (p < 0.05). There was no difference in production of these cytokines by IEL from control or inflammatory bowel disease.


Toxoplasma gondii infection in women of childbearing age of Isfahan, Iran: A population-based study.
We conducted an epidemiological survey on seroprevalence of toxoplasma infection in women of childbearing age in Isfahan Province. In a cross-sectional study in 2010, 217 women in the age range of 10-50 years were randomly selected. The blood samples examined for the presence of IgG anti-Toxoplasma gondii antibody by a commercial ELISA kit (Dia-Pro, Milan, Italy). Chi-square and Fisher's exact tests were employed to examine the antibody status in different age, marriage, education, and residence groups. The overall prevalence was 47.5% (103/217). The peak age of infection acquisition was in the range 30-40 years in rural areas and 20-30 years in urban districts. There was no significant association between residence, education, and marriage groups on the one hand and chance of T. gondii infection on the other hand. The findings of the study suggest a moderate prevalence of T. gondii infection, but a high prevalence in ages of high reproductive activities.


Molecular characterization of a new hypovirus infecting a phytopathogenic fungus, Valsa ceratosperma.
A double-stranded (ds) RNA, approximately 9.5kb in size; was identified in the MVC86 isolate of Valsa ceratosperma. Complete sequence of the dsRNA revealed a 9543-bp segment (excluding the 3' poly-A tail) that is predicted to encode a single large protein (P330). P330 has 63%, 49%, and 55% amino acid sequence identities to the proteins encoded by hypoviruses Cryphonectria hypovirus 3 (CHV3), CHV4, and Sclerotinia sclerotiorum hypovirus 1 (SsHV1), respectively. Like polyproteins encoded by CHV3, CHV4, and SsHV1, P330 comprises four conserved domains, including a papain-like protease, a UDP glucose/sterol glucosyltransferase (UGT), an RNA-dependent RNA polymerase (RdRp), and an RNA helicase. These molecular characteristics suggest that this dsRNA represents a new hypovirus that we tentatively designate Valsa ceratosperma hypovirus 1 (VcHV1). Phylogenetic analysis of the RdRp and RNA helicase domains of VcHV1 revealed that VcHV1, CHV3, CHV4, and SsHV1 clustered together into one clade distinct from that of CHV1 and CHV2, indicating the existence of two lineages in the family Hypoviridae. Comparison of biological properties between VcHV1-infected and VcHV1-free isogenic strains did not reveal differences in colony morphology or fungal virulence under laboratory conditions.


The effect of the duration and type of stress on some serum enzyme levels in pigs.
The effects of blood sampling from the ear vein, jugular vein and collection on exsanguination, on serum CK, LDH, GOT and PK activities were investigated. The activities of LDH and PK were higher in ear vein vena cava samples. The effect of pre-slaughter handling was also investigated. In general there was a significant progressive increase in serum enzyme activities from farm to slaughter, although the magnitude of the change varied for different enzymes.


A Novel In Vivo Protocol for Molecular Study of Radiation-Induced Fibrosis in Head and Neck Cancer Patients.
Radiation-induced fibrosis is a common complication for patients following head and neck cancer treatment. This study presents a novel minimally invasive protocol for molecular study of fibrosis in the stromal tissues. Subjects with radiation-induced fibrosis in the head and neck who were at least 6 months post treatment received submental core needle biopsies, followed by molecular processing and quantification of gene expression for 14 select pro-inflammatory and pro-fibrotic genes. Control biopsies from the upper arm were obtained from the same subjects. Patients were followed up at 1 and 2 weeks to monitor for safety and adverse outcomes. Six subjects were enrolled and completed the study. No subjects experienced adverse outcomes or complication. An 18 gauge core biopsy needle with a 10 mm notch inserted for up to 60 seconds was needed. Subcutaneous tissue yielded 3 ng of RNA, amplified to 6 µg of cDNA, allowing for adequately sensitive quantitative polymerase chain reaction (qPCR) analysis of approximately 28 genes. This study demonstrates the safety and utility of a novel technique for the molecular study of fibrosis in head and neck cancer patients. Longitudinal studies of patients undergoing radiation therapy will allow for identification of molecular targets that contribute to the process of fibrosis in the head and neck.


Hybrid discrete-time-continuous-time models and a SARS CoV-2 mystery: Sub-Saharan Africa's low SARS CoV-2 disease burden.
Worldwide, the recent SARS-CoV-2 virus has infected more than 670 million people and killed nearly 67.0 million. In Africa, the number of confirmed COVID-19 cases was approximately 12.7 million as of January 11, 2023, that is about 2% of the infections around the world. Many theories and modeling techniques have been used to explain this lower-than-expected number of reported COVID-19 cases in Africa relative to the high disease burden in most developed countries. We noted that most epidemiological mathematical models are formulated in continuous-time interval, and taking Cameroon in Sub-Saharan Africa, and New York State in the USA as case studies, in this paper we developed parameterized hybrid discrete-time-continuous-time models of COVID-19 in Cameroon and New York State. We used these hybrid models to study the lower-than-expected COVID-19 infections in developing countries. We then used error analysis to show that a time scale for a data-driven mathematical model should match that of the actual data reporting.


Are anti-Phl p 12 IgE levels predictive of oral allergy syndrome in profilin hypersensitive patients?
In birch pollen-allergic patients the occurrence of clinically relevant crossreactivity to plant-derived foods is clearly related with the level of birch-specific IgE. In profilin-hypersensitive patients this has not been investigated so far. To investigate whether the levels of profilin IgE are predictive of the development of food allergy in hypersensitive patients. IgE specific for Phl p 12, the grass pollen profilin, were measured in 37 subjects monosensitized to profilin with (n = 11) or without (n = 26) oral allergy syndrome (OAS) following the ingestion of plant-derived foods. Patients without a history of OAS showed higher levels of IgE specific for Phl p 12 than patients with OAS (median 4.74 [range 0.7-41.6] KU/L vs 2.14 [range 0.32-10.2] KU/L, respectively) although the difference did not reach statistical significance (p = 0.07). Factors causing the onset of OAS in profilin-hypersensitive patients remain presently unclear.


Can Ophthalmologic Examination Predict Abducens Nerve Recovery After Endoscopic Skull Base Surgery?
While abducens nerve palsy (ANP) is a known risk in the setting of some endoscopic endonasal skull base surgery (ESBS), frequency and prognosis of post-operative palsy remain unknown. Our goals were to determine the frequency and prognosis of ANP after high-risk ESBS, and identify factors associated with recovery. Retrospective case series of all patients with pathology at highest risk for abducens nerve injury (pituitary adenoma, chordoma, meningioma, chondrosarcoma, cholesterol granuloma) generated a list of patients with abducens nerve palsy after ESBS performed from 2011-2016. A validated ophthalmologic clinical grading scale measuring lateral rectus duction from 0 to -5 (full motion to inability to reach midline) was measured at multiple time points to assess recovery of ANP. Of 655 patients who underwent ESBS with increased risk of abducens injury, 40 (6.1%) post-operative palsies were identified and 39 patients with dedicated examination at multiple time points were included in subsequent analysis. Complete resolution was noted in 25 patients (64%) within 12 months. While 19 of 23 (83%) with a partial palsy had complete resolution, only six of 16 (38%) with a complete palsy resolved entirely (P = .005; Fisher's exact test). All six patients with delayed onset of palsy resolved (P = .070; Fisher's exact test). Meningioma and chordoma had higher rates of both temporary and permanent post-operative ANP (P < .0001; Fisher's exact). The frequency of post-operative ANP following ESBS is low, even in high-risk tumors. While only a minority of complete abducens nerve palsies recover, patients with partial or delayed palsy post-operatively are likely to recover function without intervention. IV Laryngoscope, 131:513-517, 2021.


Randomized Clinical Study on the Efficacy of Direct Anterior Approach Combined With Tendon Release and Repair After Total Hip Arthroplasty.
To study the effect of reconstruction of the joint capsule and conjoint tendon on the functional recovery of the hip joint during direct anterior approach (DAA) total hip arthroplasty. A total of 60 patients who underwent their first total hip arthroplasty surgery were selected. According to the set criteria, the selected patients were divided into observation group A (n = 30) and control group B (n = 30). In group A, the joint capsule and conjoint tendon (superior muscle, internal obturator muscle, and inferior muscle) were repaired in situ, while in group B, only the joint capsule was repaired in situ, and the conjoint tendon was not repaired. The surgical indicators, including hip joint function and clinical efficacy of the two groups, were compared. After 6 months of follow-up in groups A and B, no dislocation occurred. The Harris Hip scores of group A were higher than those of group B at 1-month post-operation, i.e., p < 0.05, as well as the valid muscle strength and conjoint tendon valid tension, were higher in group A than group B at 1-month postoperative follow-up, i.e., p < 0.05. DAA for total hip arthroplasty on the premise of reconstructing the joint capsule structure can rebuild the tension of the conjoint tendon, enhance its muscle strength, and significantly improve the joint stability and function of the patient early stage. It is beneficial for the patient's rapid recovery and is worth implementing.


Photoaffinity probes for serotonin and histamine receptors. Synthesis and characterization of two azide analogues of ketanserin.
Two azide analogues of ketanserin (6- and 7-azido-3-[2- [4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2, 4(1H,3H)-quinazolinedione) were synthesized and tested as possible photoaffinity probes for serotonin-S2 and histamine-H1 receptors. In reversible binding experiments, the azides showed high affinity for both receptor types. When membrane preparations were incubated with nanomolar concentrations of 7-azidoketanserin and subsequently irradiated with UV light, both serotonin and histamine receptors became irreversibly blocked. This irreversible binding was dependent on azide concentrations and time of irradiation and did not change in the presence of the scavenger p-aminobenzoic acid. In contrast, irreversible blockade at low concentrations of 6-azidoketanserin was only obtained for histamine receptors. However, this blockade was abolished by addition of the scavenger p-aminobenzoic acid indicating that it was not due to a real photoaffinity mechanism. In the rat prefrontal cortex, irreversible blocking of serotonin receptors with 7-azidoketanserin could be inhibited by serotonin agonists or antagonists but not by histaminergic compounds. On the contrary, in the guinea pig cerebellum, inactivation of histamine receptors could be inhibited by histamine antagonists and histamine itself but not by serotonergic compounds. This provides a way for differential photolabeling of either of these receptors.


Association between dental procedures and periprosthetic joint infection: A case-crossover study.
Although the risk of dental procedures as a cause of bacteremia has been recognized, evidence regarding the association between dental procedures and late periprosthetic joint infection (LPJI) is scarce. We sought to determine whether dental procedures are associated with an increased risk of LPJI. The study was conducted under a case-crossover design using a large claims database in Japan. We identified adult patients who had undergone dental procedures and were hospitalized for LPJI between April 2014 and September 2021. Exposure to dental procedures was assessed during a case period of 1-4 weeks, with two control periods of 9-12 weeks and 17-20 weeks, preceding LPJI hospital admission. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of LPJI associated with dental procedures in the case period compared with the two control periods. In total, 241 patients with LPJI were included in the case-crossover study. At least one dental procedure was performed in 46 patients (19.1%) in the hazard period and in 75 patients (31.1%) in the control periods. The OR for LPJI with dental procedures was 0.96 (95% CI, 0.61-1.53; p = 0.88). Findings were robust in several sensitivity analyses, including stratification by whether the dental procedure included antibiotic prophylaxis. This study suggests that dental procedures are not associated with increased risk of LPJI, and will raise questions about the recommendation for antibiotic prophylaxis before dental procedures.


Photodegradation performance and mechanism of sulfadiazine in Fe(III)-EDDS-activated persulfate system.
In order to overcome the shortcomings in the traditional Fenton process, Fe(III)-EDDS-activated persulfate advanced oxidation process under irradiation is carried out as a promising technology. The photodegradation of sulfadiazine (SD) in Fe(III)-EDDS-activated persulfate system was investigated in this paper. The results showed that SD could be effectively degraded in Fe(III)-EDDS/S2O82-/hv system. The effects of Fe(III):EDDS molar ratio, the concentration of Fe(III)-EDDS, and the concentration of S2O82- on SD degradation were explored. At neutral pH, when Fe(III):EDDS = 1:1, Fe(III)-EDDS = 0.1 mM, S2O82- = 1.5 mM, the best SD degradation was achieved. The experiment of external influence factors showed that the degradation of SD could be obviously inhibited by the presence of CO32-, SO42-, whereas the degradation of SD was almost unaffected by the addition ofCl-. The degradation of SD could be slightly inhibited by the presence of humic acid and NO3-. The effect of pH on SD degradation was investigated, and SD could be degraded effectively in the pH range of 3-9. ESR proved that 1O2, ·OH, SO4-, and O2- were produced in the process. SO4- and ·OH were identified as the main radicals while O2·- also played non-ignorable role. Eleven intermediate products of SD were analysed. The C = N, S-N, and S-C bonds of SD were attacked by radicals firstly, leading to a series of reactions that eventually resulted in the destruction of SD molecules and the formation of small organic molecules.


Better discrimination of hip fracture using bone density, geometry and architecture.
Bone density predicts the risk of hip fracture. Because hip strength is determined by bone geometry and architecture as well as density, we tested which variables in geometry and architecture were independent discriminators of hip fracture and, if combined with density, improved the discrimination of fracture from non-fracture over bone density alone. The design was a case-control study. The subjects were Caucasian women over the age of 60 years who had sustained a hip fracture after the age of 58 years (n = 22), and controls matched for age and weight (n = 43) and unmatched controls (n = 317) with no history of hip fracture. Variables in density, geometry and architecture were obtained from dual-energy X-ray absorptiometry images and from radiographs of the upper end of the femur. In a univariate model, of the measures of bone mass, the best discriminator of hip fracture was bone mineral density of the neck of femur; of the geometric measurements, it was hip axis length; and of the measurements of bone architecture, it was Singh grade. In a multivariate model, these three variables were shown to be independent discriminators of hip fracture. When hip axis length was combined with bone mineral density, there was significant improvement in discrimination of hip fracture (p = 0.014), and when Singh grade was combined with hip axis length and bone mineral density there was a further significant improvement (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)


Echographic evaluation of the incrustation of intrauterine contraceptive devices (IUD).
The ultrasonographic study of Intrauterine Contraceptive Devices (IUD) is reported. In their earlier investigations authors have shown that, after a prolonged use of IUD, incrustation develops over the surface of the IUD. The presence of an incrustate could be observed both during in vitro as well as in vivo ultrasonographic studies.


Endogenous sex hormone levels and breast cancer risk.
Sex-steroid hormones are a major determinant of the risk of breast cancer. We evaluated the relationship between obesity and endogenous estrogen levels in 79 healthy, postmenopausal women. Thirty-nine of the women were siblings of patients with postmenopausal-onset breast cancer; the remaining women were age-matched (+/- 10 yr) controls. Our hypothesis was that the siblings of the breast cancer patients would weigh more and that this excess weight would lead to higher serum estrone levels. The choice of unaffected family members of breast cancer patients reduces the concern that results may have been influenced by the cancer rather than antecedent to its development. Our findings demonstrated a statistically significant excess estrone level in the siblings compared to the controls (58.9 vs 47.8 pg/ml, P = 0.005). The siblings weighed 4.3 kg more than the controls. Matched pairs analysis (sibling-control), adjusting for weight, also showed significant differences in serum estrone levels. These differences were observed despite comparability in dietary intake, medication use, and personal medical history. These findings represent the first time that higher estrogen levels have been measured in siblings of postmenopausal breast cancer patients. This observation may represent an important link in our understanding of the relationship between genetic and environmental risk factors of breast cancer. One approach to subsequent genetic studies of breast cancer may be to focus on the possible biological determinants such as sex-steroid hormone level receptors, oncogenes, and gene products and not on the "familial aggregation" of breast cancer.


[Anal fissure: technic used to have an internal lateral anal sphincterotomy for its treatment (author's transl)].
The authors show a variant technic very simple of the Internal lateral anal sphincterotomy for treatment of chronic anal fissure. They present the description of this procedure with the designs of the different parts of the surgery.


Chalcones: Unearthing their therapeutic possibility as monoamine oxidase B inhibitors.
In the last years the continuous efforts in the development of novel and effective inhibitors of human monoamine oxidases (hMAOs) promoted the discovery of new agents able to effectively and selectively bound one of the two isoforms (hMAO-A and hMAO-B). However, the parent chalcone scaffold still covers an important role in hMAOs inhibition. In the present work, we focused our attention on the researches performed in the last five years, involving chalcones or compounds that can be correlated to them. We classified the chalcones into different groups depending on their structural characteristics or common molecular properties. In this regard, we also considered chalcones based on heterocycles and compounds endowed with scaffolds containing a masked chalcone motif. When structural attributes could not be used, we took advantage of enzymatic activity to arrange compounds in a group. We followed this approach for the multitarget agents. Finally, we also analysed the naturally occurring chalcones. All the sections were discussed exhaustively and the structure-activity relationship (SAR) analyses were sustained by means of detailed images describing the effects related to the substituents or structural changes.


COVID-19 in patients with diabetes: factors associated with worse outcomes.
Diabetes is one of the major comorbidities associated with COVID-19. We aimed to determine the clinical and epidemiological factors associated with the mortality of COVID-19 in diabetic patients in Iran, and also the impact of prescribed antiviral and antibiotics on patients' status. In this study, we used the national registry of hospitalized patients with Severe Acute Respiratory Syndrome (SARS) Symptoms with diabetes from February 18, 2020, to December 22, 2020. Demographic, clinical features, treatments, concurrent comorbidities, and their associations with mortality and severity outcomes were assessed using logistic regression. 78,554 diabetic in-patients with SARS symptoms were included from 31 provinces of whom 37,338 were PCR positive for COVID-19. Older age and male gender are associated with COVID-19 mortality in diabetic patients. CVD is the most frequent comorbidity (42%). CVD, kidney disease, liver disease, and COPD are associated comorbidities which increased the risk of mortality. The mortality rate is higher in diabetic patients comparing to patients with no comorbidities, particularly in younger age groups. The frequency of antiviral, and antibiotics in COVID-19 positive patients was 34%, and 31%, respectively. Antibiotic treatment has no association with mortality in COVID-19 patients. Diabetic patients indicate higher mortality comparing to patients without any underlying comorbidities. Restrict strategies on increasing effective health care utilization must be considered in diabetic patients, especially in those with parallel underlying comorbidities. Regarding the antibiotic resistance issue and the noticeable use of antibiotics in diabetic patients, it is recommended to prioritize an antibiotic guideline prescription in COVID-19 patients for better stewardship by countries.


FarGen: Elucidating the distribution of coding variants in the isolated population of the Faroe Islands.
Here we present results from FarGen Phase I exomes. This dataset is based on the FarGen cohort, which consists of 1,541 individuals from the isolated population of the Faroe Islands. The purpose of this cohort is to serve as a reference catalog of coding variants, and to conduct population genetic studies to better understand the genetic contribution to various diseases in the Faroese population. The first whole-exome data set comprise 465 individuals and a total of 148,267 genetic variants were discovered. Principle Component Analysis indicates that the population is isolated and weakly structured. The distribution of variants in various functional classes was compared with populations in the gnomAD dataset; the results indicated that the proportions were consistent across the cohorts, but probably due to a small sample size, the FarGen dataset contained relatively few rare variants. We identified 19 variants that are classified as pathogenic or likely pathogenic in ClinVar; several of these variants are associated with monogenetic diseases with increased prevalence in the Faroe Islands. The results support previous studies, which indicate that the Faroe Islands is an isolated and weakly structured population. Future studies may elucidate the significance of the 19 pathogenic variants that were identified. The FarGen Phase I dataset is an important step for genetic research in the Faroese population, and the next phase of FarGen will increase the sample size and broaden the scope.


Increased ability of transgenic plants expressing the bacterial enzyme ACC deaminase to accumulate Cd, Co, Cu, Ni, Pb, and Zn.
Transgenic tomato plants Lycopersicon esculentum (Solanaceae) cv. Heinz 902 expressing the bacterial gene 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, under the transcriptional control of either two tandem 35S cauliflower mosaic virus promoters (constitutive expression), the rolD promoter from Agrobacterium rhizogenes (root specific expression) or the pathogenesis related PRB-1b promoter from tobacco, were compared to non-transgenic tomato plants in their ability to grow in the presence of Cd, Co, Cu, Mg, Ni, Pb, or Zn and to accumulate these metals. Parameters that were examined include metal concentration and ACC deaminase activity in both plant shoots and roots; root and shoot development; and leaf chlorophyll content. In general, transgenic tomato plants expressing ACC deaminase, especially those controlled by the PRB-1b promoter, acquired a greater amount of metal within the plant tissues, and were less subject to the deleterious effects of the metals on plant growth than were non-transgenic plants.


Alterations of functional connectivity in young people with depression mediate the relationship between sleep quality and cognitive function.
Sleep disturbances is common in young people with depression, and poor sleep quality affects the ability to learn. In this study, we examined possible resting-state functional connectivity abnormalities between regions of interest, and clarified the relationship with depressive symptoms, sleep quality, and cognitive function. Resting-state functional magnetic resonance imaging (fMRI) was collected on 42 healthy controls (HCs), 82 youth depressive patients (44 without sleep disturbances (NSD), and 38 with sleep disturbances (SD)). Regions of interest were defined by using Brainnetome Atlas. Functional connectivity was calculated, and its associations with depressive symptoms, sleep quality, and cognitive function were examined using correlation analysis and mediation analysis. The left and right caudal of cingulate gyrus, tongue and larynx region of postcentral gyrus were significant brain regions in NSD versus SD. The average functional connectivity between these regions was associated with poor sleep quality (r = 0.368, p = 0.001) and worse working memory (r = -0.256, p = 0.023) and mediated the relationship between sleep quality and working memory (c = -0.738, c' = -0.500). Data consistency in this study was not good enough. This study did not monitor sleep rhythms to provide objective sleep-related data. The functional connectivity between the left and right caudal of cingulate gyrus with tongue and larynx region of postcentral gyrus may be the neural mechanism by which sleep disturbances affect working memory. This provides an intervention target for clinically improving cognitive function in young people with depression.


Measurement of head and neck paragangliomas: is volumetric analysis worth the effort? A method comparison study.
The aim of this study was to assess the reproducibility of different measurement methods and define the most workable technique for measuring head and neck paragangliomas, to determine the best method for evaluating tumour growth. The evaluation of tumour growth is vital for a 'wait-and-scan' policy, a management strategy that became increasingly important. Method comparison study. Thirty tumours, including carotid body, vagal body, jugulotympanic tumours and conglomerates of multiple tumours, were measured in duplicate, using linear dimensions, manual area tracing and an automated segmentation method. Reproducibility was assessed using the Bland-Altman method. The smallest detectable difference using the linear dimension method was 11% for carotid body and 27% for vagal body tumours, compared with 17% and 20% for the manual area tracing method. Due to the irregular shape of paragangliomas in the temporal bone and conglomerates, the manual area tracing method showed better results in these tumours (26% and 8% versus 54% and 47%). The linear dimension method was significantly faster (median 4.27 versus 18.46 minutes, P < 0.001). The automatic segmentation method yielded smallest detectable differences between 39% and 75%, and although fast (2.19 ± 1.49 minutes), it failed technically. Due to a relatively good reproducibility, fast and easy application, we found the linear dimension method to be the most pragmatic approach for evaluation of growth of carotid and vagal body paragangliomas. For jugulotympanic tumours, the preferred method is manual area tracing. However, volumetric changes of these tumours may be of less clinical importance than changes in relation to surrounding anatomical structures.


Comparative thermal ecology of two lizards.
In a habitat judged to be energetically costly for thermoregulation, mean body temperatures (MBT's) ofAnolis sagrei are significantly higher than those ofA. distichus. As indexed by the slope of the regression of body temperatures (T b ) on substrate temperature (T s ),A. sagrei is more dependent upon environmental temperatures thanA. distichus.In a habitat judged to be less costly for thermoregulation and where interspecific competition for perch sites may be less, MBT's ofA. sagrei are significantly higher, proportionally more lizards occupy sunny perches, and the slope of the regression of T b on T s is significantly less, than for conspecifics in the costly habitat.As indexed by length-specific fat body weights, well-nourished lizards in the costly habitat have T b 's which are independent of environmental temperature; T b 's of poorly-nourished lizards are highly dependent upon environmental temperature. This relationship does not hold for lizards in the low-cost habitat.These results corroborate the hypothesis that energetic costs are important in controlling the extent to which lizards thermoregulate. In high-cost habitats lizards thermoregulate less precisely than in low-cost habitats. Lizards that exploit the habitat as if it were highly productive thermoregulate more precisely than lizards that exploit the environment as if it were of low productivity.


Late-onset chest wall abscess due to a biodegradable rib pin infection after lung transplantation.
A 55-year-old man with end-stage emphysema underwent a right single-lung transplantation through a posterolateral thoracotomy. The fifth rib was divided and fused back using a biodegradable pin made of polylactide acid and hydroxyapatite. Two weeks postoperatively, he suffered from central vein catheter-related sepsis due to methicillin-sensitive Staphylococcus aureus. After being successfully treated for sepsis, he was discharged. However, 3 months later, computed tomography revealed multiple loculated abscesses in the chest wall and the right pleural space. Reoperative thoracotomy revealed abscesses mainly located around the fifth rib, where the pin was inserted. Both cultures of the abscess and the fifth rib were positive for methicillin-sensitive S. aureus, which suggested that the rib pin was the cause of the secondary infection. This case suggests the rib pins, even if they are biodegradable, could have a risk of infections side effect especially for the immunosuppressed patients.


Web-based resources for clinical bioinformatics.
In the post-Human Genome Project era, awareness of the resources available through the internet is essential to both molecular biologists and clinicians. An overview of the main databases and analytical tools described in this chapter is important to understand the principles upon which hypotheses are generated, experiments are based and conclusions reached. Similarly, an introduction to the terminology of these resources often facilitates their use and adoption into practice. This chapter covers database resources such as NCBI/ Entrez, Ensembl and UCSC as well as analytical tools for sequence alignment, promoter analysis and molecular interactions.


Evolutionary variation between a monomer and a dimer arginine kinase. Purification of the enzyme from Holothuria forskali and a comparison of some properties with that from Homarus vulgaris.
1. A purification procedure for the dimeric arginine kinase of the sea cucumber Holothuria forskali is described. 2. The enzyme has a mean molecular weight of 77250 and is composed of two equal, dissociable subunits. 3. It also shows co-operativity between substrate binding at one catalytic site to a much greater extent than the nomomeric lobster arginine kinase for which such co-operativity could not be detected unambiguously. The constants for substrate binding are reported assuming that the enzyme follows rapid-equilibrium random kinetics. From a comparison with other species, the development of co-operativity between the nucleotide- and guanidine-binding sites on one subunit is suggested to have occurred more than once in the evolution of the phosphagen kinases and is not dependent on subunit aggregation. 4. Both enzymes show similar pH profiles for thermal inactivation at 22 degrees C and have very similar stabilities. Above 40 degrees C the dimeric enzyme is much more stable than the monomer. Rate constants for heat inactivation and Arrhenius activation energies are reported. 5. The dimeric enzyme is also more stable to urea inactivation. Substrates and argininic acid all improve the stability of both enzymes. The effects of individual substrates are more distincitive with the dimeric enzymes and increase its stability to an extent that makes it about as stable as dogfish creatine kinase. In the physiological range dimerization does not seem to confer any particular advantage with respect to stability over the monomer form.


The mitochondria-rich cell of frog skin as hormone-sensitive "shunt-path".
Further investigations about the role of the mitochondria-rich cell (MR cell) in hormone-mediated transport regulation in the epithelium of frog skin brought the following results: Unlike toad bladder, in frog skin the spontaneous potential difference cannot be reversed when Na transport is blocked. A similar situation is obtained when, in addition to transport-blockade, one applies a chemical gradient for chloride to the epithelium. Under these conditions we found that in the intact preparation as well as in the separated epithelium: (i) the reversed current (RC) is linearly related to the number of MR cells; (ii) RC is mainly carried by a passive, transcellular chloride flux inwards and (iii) RC is sensitive to nor-adrenaline (10(-7) M). The beta-blocker propranolol abolishes this effect. We propose that the MR cells are the sites of transepithelial shunt-path and that this chloride flux is transcellular. As it is hormone sensitive, it could be an important regulatory instrument for the regulation of overall salt transport (internal shorting).


Protocol for detection of ferroptosis in cultured cells.
Mammalian cells can die by apoptosis or by one of several non-apoptotic mechanisms, such as ferroptosis. Here, we present a protocol to distinguish ferroptosis from other cell death mechanisms in cultured cells. We describe steps for seeding cells, administering mechanism-specific cell death inducers and inhibitors, and measuring cell death and viability. We then detail the use of molecular markers to verify mechanisms of cell death. This protocol can be used to identify and distinguish ferroptosis in 2D and 3D cultures. For complete details on the use and execution of this protocol, please refer to Ko, et al. (2019),1 Magtanong, et al. (2022),2 and Armenta, et al. (2022).3.


Relationships between POPs and baseline corticosterone levels in black-legged kittiwakes (Rissa tridactyla) across their breeding cycle.
Chronic exposure to persistent organic pollutants (POPs) in wildlife might alter the response to environmental changes through interference with the regulation of stress hormones. Here, we examined the relationship between blood concentrations of several POPs and baseline plasma corticosterone levels in the black-legged kittiwake (Rissa tridactyla) during three distinct periods in the breeding season. The concentrations of POPs and corticosterone increased, whereas body mass decreased progressively from the pre-laying period to the incubation and the chick rearing period. ∑PCB (polychlorinated biphenyls) correlated positively with the baseline corticosterone levels during the pre-laying period, which might suggest that PCBs affect the regulation of corticosterone. However, this relationship was not found during the incubation or the chick rearing period. Possible explanations are discussed with emphasis on how total stress/allostatic load is handled during different periods and conditions.


Autophagy in Cancer Chemoprevention: Identification of Novel Autophagy Modulators with Anticancer Potential.
Cancer cells have the ability to tolerate extreme conditions, autophagy-related stress tolerance enables cancer cells to survive by maintaining energy production that leads to cell growth and therapeutic resistance. Insufficient activation of autophagy in nutrient-deprived cancer cells may sensitize cancer cells to a broad array of chemotherapeutic agents and ionizing radiation. Therefore, identification of novel autophagy modulators with lower toxicity and better therapeutic index would be beneficial for cancer therapy. Here, we describe several currently used biochemical methods to assess autophagic activity and lysosomal function in cultured cancer cells. We also discuss both in vitro and in vivo assays to clarify the anticancer potential of novel autophagy modulators.


Charting Directions for Research on Immigrant Children Affected by Undocumented Status.
Three groups of children from Mexico and Central America are vulnerable to effects of US immigration policies: 1) foreign-born children who entered the US with undocumented immigrant parents; 2) unaccompanied children who entered the US alone; and 3) U.S.-born citizen children of undocumented immigrant parents. Despite the recent demographic growth of these youth, scholarship on their strengths and challenges is under-theorized and isolated within specific disciplines. Hence, service providers, researchers, and policymakers have insufficient research to inform their efforts to support the children's wellbeing. A group of scholars and service-providers with expertise in immigrant children convened to establish consensus areas and identify gaps in knowledge of undocumented, unaccompanied, and citizen children of undocumented immigrant parents. The primary goal was to establish a research agenda that increases interdisciplinary collaborations, informs clinical practice, and influences policies. This report summarizes key issues and recommendations that emerged from the meeting.