Oscillometric arterial blood pressure in haemodynamically stable neonates in the first 2 weeks of life.
We aimed to provide data on the normal blood pressure of haemodynamically stable neonates. Our study uses retrospective, real-life oscillometric blood pressure measurement values to determine the expected blood pressure in different gestational age, chronological age and birth weight groups. We also investigated the effect of antenatal steroid on neonatal blood pressure. Our retrospective study (2019-2021) was carried out in the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We involved 629 haemodynamically stable patients and analysed 134,938 blood pressure values. Data were collected from electronic hospital records of IntelliSpace Critical Care Anesthesia by Phillips. We used the PDAnalyser program for data handling and the IBM SPSS program for statistical analysis. We found a significant difference between the blood pressure of each gestational age group in the first 14 days of life. The systolic, diastolic and mean blood pressure rise are steeper in the preterm group than in the term group in the first 3 days of life. No significant blood pressure differences were found between the group with a complete antenatal steroid course and those who received incomplete steroid prophylaxis or did not receive antenatal steroids. We determined the average blood pressure of stable neonates and obtained normative data by percentiles. Our study provides additional data on how blood pressure varies with gestational age and birth weight. A higher resolution version of the Graphical abstract is available as Supplementary information.


Effects of Exercise and Enzyme Therapy in Early Occupational Carpal Tunnel Syndrome: A Preliminary Study.
Occupational carpal tunnel syndrome (CTS) due to upper extremity overuse has in recent years been the most commonly recognized occupational disease in the Czech Republic and its prevalence has steadily increased. This pilot observation aimed to assess the effects of exercise techniques and oral enzyme therapy in automotive plant workers with early CTS. The observation comprised automotive plant assembly line workers in whom nerve conduction study revealed incipient CTS. The subjects were divided into three groups: a group practicing exercise techniques (exercising; N=15), a group receiving oral enzyme therapy (N=16), and a group of controls (N=14). Subjects in the control group were only observed without any specific intervention, which is a common procedure in incipient CTS. Throughout 9-week observation, the workers did their jobs. Prior to and after that period, the workers' CTS-related symptoms were ascertained through structured interviews with a physician and the following median nerve parameters were measured: sensory conduction velocity (SCV) and distal motor latency (DML). In both the exercise and enzyme therapy groups, statistically significant decreases in the total score for symptoms were achieved (p<0.0001), unlike controls. On final examination, both treated groups demonstrated significantly increased SCV as compared with the initial values (p=0.00013 and p<0.0001, respectively); in controls, the mean SCV did not significantly change. Similarly, a statistically significant shortening of DML was noted in the enzyme therapy group (p=0.008). The results showed the efficiency of both exercise and oral enzyme therapy in incipient CTS. These methods may be recommended for preventing more severe forms of CTS.


Adrenarche and middle childhood.
Middle childhood, the period from 6 to 12 years of age, is defined socially by increasing autonomy and emotional regulation, somatically by the development of anatomical structures for subsistence, and endocrinologically by adrenarche, the adrenal production of dehydroepiandrosterone (DHEA). Here I suggest that DHEA plays a key role in the coordinated development of the brain and body beginning with middle childhood, via energetic allocation. I argue that with adrenarche, increasing levels of circulating DHEA act to down-regulate the release of glucose into circulation and hence limit the supply of glucose which is needed by the brain for synaptogenesis. Furthermore, I suggest the antioxidant properties of DHEA may be important in maintaining synaptic plasticity throughout middle childhood within slow-developing areas of the cortex, including the insula, thamalus, and anterior cingulate cortex. In addition, DHEA may play a role in the development of body odor as a reliable social signal of behavioral changes associated with middle childhood.


Brain Structures Implicated in Inflammation-Associated Depression.
Systemic inflammation rapidly impairs mood, motivation, and cognition inducing a stereotyped cluster of symptoms collectively known as "sickness behaviors." When inflammation is severe or chronic, these behavioral changes can appear indistinguishable from major depressive disorder (MDD). Human and rodent neuroimaging combined with experimental inflammatory challenges has clarified the neural circuitry associated with many of the key features of inflammation-induced-sickness behavior, and in so doing revealed often-remarkable commonalities with circuit abnormalities observed in MDD. This review aims to provide the first synthesis of this work illustrating areas of convergence and divergence with the MDD literature as well as highlighting areas for future study.


Introduction of cloned human papillomavirus genomes into mouse cells and expression at the RNA level.
The entire DNA genomes of five different human papillomaviruses (HPVs) were cloned into the BamHI site of pBR322 (HPV-1a, HPV-3, HPV-4, and HPV-9) or the EcoRI site of pBR325 (HPV-2), using as starting materials virus preparations isolated from papillomas of individual patients. Under stringent hybridization conditions (Tm-28 degrees), the five cloned HPVs exhibited less than 10% homology with one another. To establish model cell systems that may be useful for the identification of HPV genes and HPV gene products, mouse thymidine kinase negative (tk-) cells were cotransformed to the tk+ phenotype with the herpesvirus thymidine kinase gene and each of the five HPV cloned DNAs (either as intact recombinants or excised HPV DNA without removal of pBR). In most tk+ cell clones, a complex pattern of multiple high molecular weight inserts of HPV DNA were present in high copy number. Most of the HPV DNA sequences in the cotransformed cells were not present as unit-length episomal viral DNA. Analyses of the integration pattern (DNA blot) and RNA expression (RNA blot) of several HPV-1a and HPV-3 transformed cell lines suggest that some copies of the viral genome are integrated in a similar manner in different cell lines leading to the expression of identical viral RNA-containing species. Two of the cell lines transformed by the intact HPV-1a/pBR322 recombinant synthesized substantial amounts of four discrete viral polyadenylated cytoplasmic RNA species of 1.9, 3.2, 3.8, and 4.5 kb. Two cell lines transformed by the intact HPV-3/pBR322 recombinant synthesized 4-5 polyadenylated cytoplasmic viral RNA species ranging from 0.8 to 4.6 kb. The analysis shows that each viral RNA species appears to be a hybrid RNA molecule containing both HPV and pBR322 sequences. Based on these findings and the molecular organization of the HPV-1a genome (O. Danos, M. Katinka, and M. Yaniv (1982). EMBO J. 1, 231-237), it is possible that transcription of each of the HPV-1a RNA species is initiated using the HPV early promoter and terminated in pBR322.


Lattice Strain Regulation Enables High-Performance Formamidinium Perovskite Photovoltaics.
Formamidinium lead iodide (FAPbI3 ) perovskite possesses an ideal optical bandgap and is a potential material for fabricating the most efficient single-junction perovskite solar cells (PSCs). Nevertheless, large formamidinium (FA) cations result in residual lattice strain, which reduces the power conversion efficiency (PCE) and operational stability of PSCs. Herein, the modulation of lattice strain in FAPbI3 crystals via a π-conjugated organic amine, i.e., 4-pyrene oxy butylamine (PYBA), is proposed. PYBA pairs at the grain boundary serve as a template for the crystallization of FAPbI3 perovskite, thereby inducing a highly oriented crystal and a pure α-phase film. The PYBA pairs with strong π-π interactions provide a solid fulcrum for external compression strain, thus compensating for the inherent tension strain of FAPbI3 crystals. The strain release elevates the valence band of the perovskite crystals, thereby decreasing the bandgap and trap density. Consequently, the PYBA-regulated FAPbI3 PSC achieves an excellent PCE of 24.76%. Moreover, the resulting device exhibits improves operational stability and maintains over 80% of its initial PCE after 1500 h under maximum power point tracking conditions.


Audit of surgical procedures in regional and central hospitals in Limpopo Province, South Africa.
There is a paucity of data on the functioning and surgical procedures performed in rural hospitals in South Africa. To determine the category of procedures performed at regional and tertiary hospitals in Limpopo Province, South Africa. We conducted a retrospective analysis of surgical procedures performed in the regional and tertiary hospitals in Limpopo Province during a 1-year period from 1 March 2019 to 29 February 2020. A total of 24 263 surgical procedures were performed during the study period. More than half of all cases (50.4%; n=12 252) were operated on at the tertiary hospitals while regional hospitals performed the remaining 12 011 operations. There is a great necessity to alleviate the central hospitals from the bulk of surgical procedures.


Odour-imagery ability is linked to food craving, intake, and adiposity change in humans.
It is well-known that food-cue reactivity (FCR) is positively associated with body mass index (BMI)1 and weight change2, but the mechanisms underlying these relationships are incompletely understood. One prominent theory of craving posits that the elaboration of a desired substance through sensory imagery intensifies cravings, thereby promoting consumption3. Olfaction is integral to food perception, yet the ability to imagine odours varies widely4. Here we test in a basic observational study whether this large variation in olfactory imagery drives FCR strength to promote adiposity in 45 adults (23 male). We define odour-imagery ability as the extent to which imagining an odour interferes with the detection of a weak incongruent odour (the 'interference effect'5). As predicted in our preregistration, the interference effect correlates with the neural decoding of imagined, but not real, odours. These perceptual and neural measures of odour imagery are in turn associated with FCR, defined by the rated craving intensity of liked foods and cue-potentiated intake. Finally, odour imagery exerts positive indirect effects on changes in BMI and body-fat percentage over one year via its influences on FCR. These findings establish odour imagery as a driver of FCR that in turn confers risk for weight gain.


Endogenous VSIG4 negatively regulates the helper T cell-mediated antibody response.
VSIG4 acts as a co-inhibitory ligand to negatively regulate T cell proliferation and cytokine production, and its expression is restricted to macrophages. We hypothesized that endogenous VSIG4 impairs helper T cell functions and then inhibits the subsequent antibody response. Isotype switching of ovalbumin (OVA)-specific antibody subclasses to IgG1, IgG2a, IgG2b, and IgG3 was enhanced in OVA-immunized VSIG4 knockout (KO) mice. 2,4,6-Trinitrophenyl hapten (TNP) - Keyhole Limpet Hemocyanin (KLH)-primed B cells cocultured with OVA-primed CD4(+) T cells from OVA-immunized VSIG4 KO mice in the presence of TNP-OVA showed enhanced isotype switching to IgG subclasses compared to those cocultured with cells isolated from OVA-immunized wild-type (WT) mice. Furthermore, the levels of CD40L expression, the frequency of memory CD4(+) T cells, and the production of isotype switching-inducing cytokines increased significantly in OVA-primed CD4(+) T cells from VSIG4 KO mice. T cells from OVA-specific T cell receptor (TCR) transgenic mice produced more IFN-γ when cocultured with macrophages from VSIG4 KO mice compared to WT mice. Thus, our results demonstrate that macrophage-associated VSIG4 plays a negative role in helper T cell-dependent isotype switching by inhibiting helper T cell activation and differentiation, and suppressing the isotype switching-inducing cytokine production in antigen-primed CD4(+) helper T cells.


Role of functional polymorphisms of NRAMP1 gene for the development of Crohn's disease.
Crohn's disease (CD) is characterized by chronic activation of macrophages. Natural resistance-associated macrophage protein 1 (NRAMP1) gene exerts many pleiotropic effects on macrophage functions. Hence, NRAMP1 may be also involved in the resistance to intracellular pathogens, and this effector of the innate immunity might be involved in CD pathogenesis. Polymorphic alleles at the NRAMP1 locus have been previously associated with susceptibility both to the putative infectious agents and to autoimmune disorders. Based on these indications, in the present study we investigate its candidacy as a genetic determinant for CD in a Greek population in an association-based study, comparing frequencies of 274 CD patients to these of 200 healthy control subjects. The 5'(GT)n promoter polymorphism and 9 either single nucleotide (SNPs) or insertion/deletion type polymorphisms were genotyped across the NRAMP1 gene. Reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry were performed in order to investigate the NRAMP1 mRNA levels in RNA isolated from biopsies of CD patients as well as protein expression in tissues. Three NRAMP1 polymorphisms [5'(GT)n, D543N, and INT4G/C] were significantly associated with CD. Consistent with previous autoimmune disease studies, allele 3 at the functional 5'(GT)n promoter region repeat polymorphism, was significantly associated with CD when compared to healthy controls (odds ratio 1.50; 95% confidence interval [CI]: 1.16-1.95; P = 0.002). Interestingly, we observed that CD patients homozygous for allele 3 expressed higher NRAMP1 mRNA levels compared to carriers of allele 2. Furthermore, the protein levels of allele 3 carriers in tissues were also elevated compared to those of allele 2 carriers. Based on these data we can speculate that overrepresentation of allele 3 in CD patients could lead to hyperactivation of bowel-wall macrophages that are chronically exposed to lipopolysaccharide and this could subsequently cause the autoimmune-like phenotype characteristic of CD. Collectively, our data indicate that genetic polymorphisms of NRAMP1 might be associated with susceptibility to CD.


[Transcatheter embolization of renal artery--alternative to preoperative renal tumour radiotherapy? (author's transl)].
Transcatheter coil embolization (according to the method of Gianturco) was performed in 18 patients. It resulted in prompt and permanent occlusion of the renal artery without considerable effort and with acceptable risk. The favourable benefit of this procedure is technical facilitation of tumornephrectomy, cutting down the time of surgery, reducing intraoperative hemorrhage and danger of venous displacement of tumor-cells. The same favourable results will not be achieved by preoperative short-time radiation. Preoperative long-term radiation delays the necessary tumor-nephrectomy. Arterial embolization is preferred because it offers the wanted benefits of sufficient radiotherapy avoiding its disadvantages.


Narcotrend index versus bispectral index as electroencephalogram measures of anesthetic drug effect during propofol anesthesia.
The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) performs an automatic analysis of the electroencephalogram (EEG) during anesthesia based on a visual assessment of the raw EEG. Its newest software version 4.0 includes a dimensionless index that, similar to the bispectral index (BIS), ranges from 100 (awake) to 0. We compared the performance of Narcotrend index and BIS as EEG measures of anesthetic drug effect during propofol anesthesia. Eighteen adult patients scheduled for radical prostatectomy were investigated. An epidural catheter was placed in the lumbar space and electrodes for BIS (version XP; Aspect Medical Systems, Natick, MA) and Narcotrend were positioned as recommended by the manufacturers. Narcotrend index, BIS values, and propofol plasma and effect site concentrations as parallelly simulated by Rugloop software (Department of Anesthesia, Ghent University, Belgium) were automatically recorded in intervals of 5 s. Induction of anesthesia consisted of a fentanyl bolus and a propofol infusion. After endotracheal intubation, patients received 15 mL bupivacaine 0.5% epidurally, and 45 min later propofol dosages were subsequently increased and decreased twice. Simulated propofol effect site concentrations ranged from 2.0 +/- 0.4 microg/mL (smallest) to 6.3 +/- 1.3 microg/mL (largest) during these subsequent increases and decreases of propofol. In terms of prediction probability (P(K)) the performance of the Narcotrend index (P(K) = 0.88 +/- 0.03) to predict propofol effect site concentrations was comparable to the BIS (P(K) = 0.85 +/- 0.04). Using the respective EEG index as a measure of drug effect the mean k(e0) was calculated as 0.20 +/- 0.05 min(-1) for Narcotrend index and 0.16 +/- 0.07 min(-1) for BIS. In the observed propofol concentration range Narcotrend index detected differences in EEG dynamics as well as BIS. This study in 18 adult patients undergoing radical prostatectomy describes the relationship between Narcotrend index and bispectral index versus predicted propofol effect compartment concentrations. In terms of prediction probability, the performance of the Narcotrend index and the bispectral index to predict propofol effect site concentrations was comparable.


Two sides of the same coin? Patient and therapist experiences with a transdiagnostic blended intervention focusing on emotion regulation.
The combination of internet-based intervention and psychotherapy, commonly termed blended therapy (BT), has gained popularity in recent years. While advantages and disadvantages of BT have been identified from the patient and therapist perspective, the two perspectives have rarely been examined within the same treatment. Moreover, almost all available research on patient and therapist experiences with BT is disorder-specific. This study aimed to investigate patient and therapist experiences within the same transdiagnostic BT. A qualitative analysis of semi-structured interviews with eight patients and eight therapists taking part in a transdiagnostic blended intervention focusing on the topic of emotion regulation was conducted. A qualitative content analysis approach was used. Category frequencies were calculated and similarities and differences between the patient and therapist experience were explored. Ten main themes and 59 subthemes were identified in the category system for patient interviews and ten main themes and 50 subthemes were identified in the category system for therapist interviews. Similarities and differences between the two perspectives were reported with regard to 1) expectations toward the intervention, 2) the internet-based intervention, 3) symptomatology and emotion regulation, 4) the therapeutic relationship and 5) the blended format. This study provides first insights on the experiences with transdiagnostic BT focusing on emotion regulation. Based on the results, different recommendations for the improvement of transdiagnostic BT are made. Future research on patient and therapist experiences with transdiagnostic BT is necessary, in order to further improve the experience of those involved.


A review of the distribution, sources, genesis, and environmental concerns of salinity in groundwater.
Awareness concerning the degradation of groundwater quality and their exacerbating adverse effects due to salinization processes is gaining traction, raising for adequate understanding of the distribution, sources, genesis, and environmental concerns of salinity in groundwater. Saline groundwater is widely distributed all over the world, with an area of 24 million km2 (16% of the total land area on earth) and 1.1 billion people living in the affected areas, especially the arid/semi-arid areas in developing countries. These large-scale groundwater salinization problems are sourced from two major ways: natural and anthropogenic. The natural sources are diversified from connate saline groundwater, seawater intrusion, evaporation, dissolution of soluble salts, membrane filtration process to geothermal origin. The anthropogenic sources include irrigation return flow, road deicing salts, industrial and agricultural wastewater, and gas and oil production activities. The integrated approach of geochemical tracers and multiple isotopes (δ18OH2O, δ2HH2O, δ11B, δ36Cl, δ34Ssulfate, 87Sr/86Sr, and δ7Li) is proved to be useful in the constraints of the origin and transport of solutes in groundwater. Groundwater salinization is often associated with high levels of some toxic elements like arsenic, fluoride, selenium, and boron. Four "triggers" lead to this association: salt effect, competing adsorption, microbial processes, and cation exchange.


Magnetic resonance imaging of entheses. Part 1.
Entheses are the sites of attachment of a tendon, ligament, or joint capsule to bone. Many features of entheses are adapted to disperse stress and accommodate compressive and shear forces at, or near, boundaries between tendons or ligaments and bone. Of particular interest is calcified and uncalcified fibrocartilage, which has mechanical properties that differ from those of tensile regions of tendons or ligaments, and from bone. Ultrashort echo time (UTE) pulse sequences can identify the specific tissue components of entheses and differentiate cortical bone, calcified fibrocartilage, uncalcified fibrocartilage, and fibrous connective tissue. Magic angle imaging can also differentiate tissues, such as fibrocartilage and tendon, which have different fibre orientations. Understanding the magnetic resonance (MR) appearance of entheses involves consideration of tissue properties, fibre-to-field angle, magic angle effects, pulse sequences, and geometrical factors including fibre-to-section orientation and partial volume effects. New approaches using MR imaging, allow entheses to be visualised with much greater detail than previously possible, and this may help in biomechanical studies, diagnosis of disease including overuse syndromes and spondyloarthropathies, as well as monitoring tissue repair and healing.


Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Müller Cells.
Memantine (MEM) acts on the glutamatergic system by blocking N-methyl-d-aspartate (NMDA) glutamate receptors. The role that MEM plays in protecting retinal cells is unknown. Hydroquinone (HQ) is one of the cytotoxic components in cigarette smoke. In the present study, we tested whether pretreatment with MEM could protect against the cytotoxic effects of HQ on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) in vitro. Cells were plated, pretreated for 6 h with 30 μM of MEM, and then exposed for 24 h to 200, 100, 50, and 25 μM of HQ while MEM was still present. Cell viability (CV), reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and lactate dehydrogenase (LDH) release assays were performed. HQ-treated cells showed a dose-dependent decrease in CV and ΔΨm, but an increase in ROS production and LDH levels in both cell lines. MEM pretreatment reversed the CV in 50, 100, and 200 μM doses in ARPE-19 cells and at all HQ concentrations in MIO-M1 cells compared to HQ-treated cultures. ROS production was reversed in all HQ concentrations in both cell lines. ΔΨm was significantly increased after MEM pretreatment only in 50 μM HQ concentration for both cell lines. LDH levels were decreased at 50 and 25 μM HQ in ARPE-19 and MIO-M1 cells, respectively. HQ-induced toxicity is concentration dependent in ARPE-19 and MIO-M1 cultures. MEM exerts protective effects against HQ-induced toxicity on human retinal pigment epithelial and Müller cells in vitro.


Molecular identification of biwa trout (Oncorhynchus masou rhodurus) using PCR-RFLP method.
Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to identify meat from biwa trout (Oncorhynchus masou rhodurus), amago trout (Oncorhynchus masou ishikawae), yamame trout (Oncorhynchus masou masou), and rainbow trout (Oncorhynchus mykiss). PCR amplification was conducted using primers flanking conserved regions of NADH dehydrogenase subunits 4 and 5 (ND4-ND5) (2848 bp) and ND1 (1091 bp) genes of mitochondrial DNA following restriction digestion with the enzyme HaeIII. Although the segments of ND4-ND5 and ND1 genes showed intraspecies variation, the generation of DNA fragments larger than 300 bp and 160 bp following cleavage by HaeIII of ND4-ND5 and ND1, respectively, was efficient to differentiate the four species. Furthermore, this method was successful in species identification even when using PCR-amplified products obtained from thermally processed biwa trout samples. This sensitive technique can be utilized to reveal commercial fraud, where biwa trout is adulterated with meat from cheaper counterparts.


Parameters affecting the maximum cell concentration of Tetrahymena.
In cultures with efficient aeration a maximum cell concentration (MCC) of 6 X 10(5) cells/ml (defined medium) and 5.5 X 10(6) cells/ml (broth) can be reached. By culturing within Millicells with excess supply of medium and efficient removal of waste products a physical limit for MCC of about 13 X 10(6) cells/ml is reached.


Noninvasive biophysical assessments of the efficacy of a moisturizing cosmetic cream base for patients with atopic dermatitis during different seasons.
The use of emollients is recommended for patients with atopic dermatitis (AD) to maintain improved condition. To ascertain objectively the effectiveness of a moisturizing cream for patients with AD during different seasons. We conducted clinical evaluations, noninvasive biophysical measurements and biochemical analyses of the stratum corneum (SC) components of the volar forearm skin of 23 patients with AD after a moisturizer was applied twice daily for 4 weeks. The moisturizer was formulated according to the consensus of cosmetic scientists belonging to major Japanese cosmetic companies. The nontreated forearm served as a control. After using the moisturizer treatment, the hydration of the SC significantly increased together with a decrease in the desquamation measurements and an improvement in the regularity of skin surface corneocytes. An improvement was observed in the SC barrier function in winter, but was achieved only after 4 weeks in late spring during which time there even occurred exacerbation of skin conditions in three patients. With use of the moisturizer treatment, we found no change in the SC content of free amino acids or ceramides, the ratio of interleukin (IL)-1 receptor antagonist to IL-1alpha, the ratio of immature to mature cornified envelopes, the size of the corneocytes or the emergence of parakeratotic cells in the skin surface corneocytes. Treatment with an adequate moisturizer is beneficial for the dry skin of patients with AD during the dry, cold season but it does not influence the impaired SC barrier function as effectively in the less arid season.


The effect of queen ants on the survival of Maculinea arion larvae in Myrmica ant nests.
The mortality of Maculinea arion caterpillars was measured in both laboratory and wild Myrmica nests, and found to be nearly 3 times higher in nests that had queen ants present. This is attributed to 'queen effect', which causes worker ants in nests with queens to attack large ant larvae (gynes) that would otherwise develop into new queens. Maculinea arion caterpillars mimic Myrmica larvae, and are usually attacked during the first 10 days after adoption, when they pass through the size range of ant gyne larvae. Caterpillars are also likely to be attacked during this period because their nethod of feeding brings them into close contact with the skins of large ant larvae, which contain gyne larval pheromones; older caterpillars are large enough to eat larvae without their exposed surfaces contacting the larval skin. In the wild, many caterpillars of Maculinea arion die in ant nests, and this has been shown in previous work to be the key factor that determines changes in their abundance from year to year. It is suggested that queen effect can be an important cause of these deaths, and one that particularly affects populations of butterflies that breed on sites with long-established plagioclimaxes of short turf rather than short-lived grass-land successions.


Development and validation of a novel algorithm based on the ECG magnet response for rapid identification of any unknown pacemaker.
Pacemaker (PM) interrogation requires correct manufacturer identification. However, an unidentified PM is a frequent occurrence, requiring time-consuming steps to identify the device. The purpose of this study was to develop and validate a novel algorithm for PM manufacturer identification, using the ECG response to magnet application. Data on the magnet responses of all recent PM models (≤15 years) from the 5 major manufacturers were collected. An algorithm based on the ECG response to magnet application to identify the PM manufacturer was subsequently developed. Patients undergoing ECG during magnet application in various clinical situations were prospectively recruited in 7 centers. The algorithm was applied in the analysis of every ECG by a cardiologist blinded to PM information. A second blinded cardiologist analyzed a sample of randomly selected ECGs in order to assess the reproducibility of the results. A total of 250 ECGs were analyzed during magnet application. The algorithm led to the correct single manufacturer choice in 242 ECGs (96.8%), whereas 7 (2.8%) could only be narrowed to either 1 of 2 manufacturer possibilities. Only 2 (0.4%) incorrect manufacturer identifications occurred. The algorithm identified Medtronic and Sorin Group PMs with 100% sensitivity and specificity, Biotronik PMs with 100% sensitivity and 99.5% specificity, and St. Jude and Boston Scientific PMs with 92% sensitivity and 100% specificity. The results were reproducible between the 2 blinded cardiologists with 92% concordant findings. Unknown PM manufacturers can be accurately identified by analyzing the ECG magnet response using this newly developed algorithm.


Physiological function of descending noradrenaline projections to the spinal cord: role in post-decapitation convulsions.
Destruction of the descending noradrenergic innervation to the spinal cord, but not that to the cerebellum or the forebrain, by the use of intracerebral injection of 6-hydroxydopamine completely prevented the occurrence of the usual itation convulsion. Depletion of brain noradrenaline by synthesis inhibition with DDC, FLA 57 or FLA 63 g reduced the duration of the post-decapitation convulsion. Blockade of alpha-noradrenergic receptors by phentolamine or phenoxybenzamine, but not of beta-receptors by propranolol, also reduced the duration of the convulsion. The presynaptic alpha-agonist, clonidine, at either 1 mg/kg or 0.05 mg/kg also reduced the magnitude of the convulsion but either blockade of dopamine receptors with pimozide or destruction of the ascending dopamine systems by 6-hydroxydopamine was without effect. It is concluded that dopamine systems are not involved in post-decapitation convulsions and that the noradrenergic involvement is by the descending spinal projections acting on a post-synaptic alpha-receptor in the spinal cord, but also modulated by presynaptic alpha-receptors possibly on the locus coeruleus perikarya.


Tuning the photophysical properties of lanthanide(iii)/zinc(ii) 'encapsulated sandwich' metallacrowns emitting in the near-infrared range.
A family of Zn16Ln(HA)16 metallacrowns (MCs; Ln = YbIII, ErIII, and NdIII; HA = picoline- (picHA2-), pyrazine- (pyzHA2-), and quinaldine- (quinHA2-) hydroximates) with an 'encapsulated sandwich' structure possesses outstanding luminescence properties in the near-infrared (NIR) and suitability for cell imaging. Here, to decipher which parameters affect their functional and photophysical properties and how the nature of the hydroximate ligands can allow their fine tuning, we have completed this Zn16Ln(HA)16 family by synthesizing MCs with two new ligands, naphthyridine- (napHA2-) and quinoxaline- (quinoHA2-) hydroximates. Zn16Ln(napHA)16 and Zn16Ln(quinoHA)16 exhibit absorption bands extended into the visible range and efficiently sensitize the NIR emissions of YbIII, ErIII, and NdIII upon excitation up to 630 nm. The energies of the lowest singlet (S1), triplet (T1) and intra-ligand charge transfer (ILCT) states have been determined. LnIII-centered total (Q L Ln) and intrinsic (Q Ln Ln) quantum yields, sensitization efficiencies (η sens), observed (τ obs) and radiative (τ rad) luminescence lifetimes have been recorded and analyzed in the solid state and in CH3OH and CD3OD solutions for all Zn16Ln(HA)16. We found that, within the Zn16Ln(HA)16 family, τ rad values are not constant for a particular LnIII. The close in energy positions of T1 and ILCT states in Zn16Ln(picHA)16 and Zn16Ln(quinHA)16 are preferred for the sensitization of LnIII NIR emission and η sens values reach 100% for NdIII. Finally, the highest values of Q L Ln are observed for Zn16Ln(quinHA)16 in the solid state or in CD3OD solutions. With these data at hand, we are now capable of creating MCs with desired properties suitable for NIR optical imaging.


Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.
Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ≥ 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ≥ 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days.


Characterization of a G-protein beta-subunit gene from the nematode Caenorhabditis elegans.
The gene encoding the beta-subunit of guanine nucleotide binding regulatory proteins (G-proteins) has been cloned from the nematode Caenorhabditis elegans. The predicted 340 amino acid sequence matches the highly conserved amino acid sequences of previously isolated G-protein beta-subunits from mammals and Drosophila. The coding region of the C. elegans beta-subunit gene, which has been mapped to the C. elegans chromosome II, is interrupted by eight introns. Southern analysis indicates that C. elegans has only one beta-subunit gene. A 2.8 kb (1 kb = 10(3) bases or base-pairs) transcript derived from this gene could be detected.


Molecular evaluation of apoptotic versus antiapoptotic angiogenic markers in hepatocellular carcinoma.
To assess the role of HO-1 in HCC progression and to study the expression of apoptotic factors represented by TNF-alpha, and Fas-L versus antiapoptotic and angiogenic factors represented by HO-1, TGF-beta, HGF, and VEGF in HCC compared to non cancerous cirrhotic liver. Liver biopsies were taken from twelve patients with grade II HCC confined to the liver and twelve patients with non cancerous liver cirrhosis (served as control). RT-PCR of previous genes was evaluated. HO-1, VEGF, HGF, and TNF-alpha genes were significantly increased (P<0.05) in HCC compared to control. Fas-L showed a significant decrease (P<0.05) in HCC compared to control. TGF-beta was higher in HCC than control but the difference was not statistically significant (P>0.05). HGF showed significant positive correlation with HO-1 (r=0.8217, P=0.001). HCC is associated with increased expression of VEGF, HGF, and TGF-beta, and with suppression of Fas-L. In addition, HO-1 is highly significantly expressed in HCC. The significant positive correlation between HO-1 and HGF was first reported in Egyptian human liver biopsies, and this suggests that it may play a role in the progression of hepatocellular carcinoma.


Isolated mitral replacement with stent-mounted antibiotic-treated aortic allograft valves.
The results of valve replacement with a stent-mounted antibiotic-treated aortic allograft valve are reported in 129 patients with isolated mitral valve disease. Of these patients, 70 per cent were in N.Y.H.A. Class IV. The hospital mortality rate was 3.9 percent. The cumulative complication-free rate at 5 years was only 37 percent as 21 percent died late, a further 15 percent were alive following reoperation, 4 percent had an embolic episode, 4 percent were alive with important incompetence, and 20 percent had unimportant incompetence. Proved valve failure was due mainly to detachment of the aortic wall remnant of the valve from the pillar of the rigid metal stent (16 percent incidence at 5 years) and methods for preventing this complication are discussed. Because of these complications the use of this device in the mitral position has been discontinued.


Effects of renal tubular dysfunction on bone in tenofovir-exposed HIV-positive patients.
Tenofovir disoproxil fumarate (TDF) may cause renal tubular dysfunction (RTD) and reduce bone mineral density (BMD). We examined the relationship between RTD and BMD in TDF-exposed HIV-positive men. We analysed urinary retinol-binding protein/creatinine ratio (RBPCR) and fractional excretion of phosphate (FEPO4) to quantify RTD in a cross-sectional sample of randomly selected HIV-positive men at a single tertiary outpatient clinic. BMD at the lumbar spine and hip was measured by dual-energy X-ray absorptiometry. Multivariate logistic regression was used to analyse factors associated with RTD, and linear regression to examine the relationship between RTD and BMD. Of 293 men (mean age 48 years, 94% White ethnicity, median TDF exposure 2.1 years), 22.5% had RBPCR-defined RTD and 12.3% had FEPO4-defined RTD. We observed a negative correlation between RBPCR and BMD at the spine (β -0.2, P = 0.002) and hip (total: β -0.1, P = 0.02; femoral neck: β -0.1, P = 0.02), but not between FePO4 and BMD. In multivariable analyses, RTD defined by more than five-fold elevations in RBPCR was associated with significantly lower BMD of the spine. In HIV-positive patients receiving TDF-containing antiretroviral therapy, RTD was associated with lower BMD of the spine in HIV-positive men. RBPCR quantification may identify patients at increased risk of TDF-associated BMD loss.


Genetically engineered zebrafish as models of skeletal development and regeneration.
Zebrafish (Danio rerio) are aquatic vertebrates with significant homology to their terrestrial counterparts. While zebrafish have a centuries-long track record in developmental and regenerative biology, their utility has grown exponentially with the onset of modern genetics. This is exemplified in studies focused on skeletal development and repair. Herein, the numerous contributions of zebrafish to our understanding of the basic science of cartilage, bone, tendon/ligament, and other skeletal tissues are described, with a particular focus on applications to development and regeneration. We summarize the genetic strengths that have made the zebrafish a powerful model to understand skeletal biology. We also highlight the large body of existing tools and techniques available to understand skeletal development and repair in the zebrafish and introduce emerging methods that will aid in novel discoveries in skeletal biology. Finally, we review the unique contributions of zebrafish to our understanding of regeneration and highlight diverse routes of repair in different contexts of injury. We conclude that zebrafish will continue to fill a niche of increasing breadth and depth in the study of basic cellular mechanisms of skeletal biology.


Pediatric surgery on YouTube™: is the truth out there?
In 2000, we described the variability of pediatric surgical information on the Internet. Since then, online videos have become an increasingly popular medium for education and personal expression. The purpose of this study was to examine the content and quality of videos related to pediatric surgical diagnoses on the Internet. YouTube™ was searched for videos on gastroschisis, congenital diaphragmatic hernia, pediatric inguinal hernia, and pectus excavatum. The first 40 English language videos for each diagnosis were reviewed for owner and audience characteristics, content and quality. A small majority of videos were made by medical professionals (50.63%, vs. 41.25% by lay persons and 8.13% by fundraising organizations). Eighty percent of videos were intended for a lay audience. Videos by medical professionals were more accurate and complete than those posted by lay persons. The YouTube™ videos varied significantly in content and quality. Videos by lay persons often focused on the emotional aspect of the diagnosis and clinical course. Videos by members of the medical profession tended to be more complete and accurate. These findings underscore the continued need for high quality pediatric surgical information on the Internet for patients and their families.


Author Correction: The population structure of Clostridium tetani deduced from its pan-genome.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


A synthetic peptide induces a new anti-dextran idiotype.
We have synthesized the JH1 peptide and coupled it to keyhole limpet haemocyanin for use as an immunogen. A serum from an animal hyperimmunized with this immunogen demonstrated binding to both peptide and native immunoglobulin. Furthermore, this serum seems to define an idiotypic determinant nearly unique to alpha (1 ---- 3) dextran-binding immunoglobulins. Synthetic peptide immunogens may be a useful tool in probing the molecular basis of idiotypy.


Hypoxia in solid tumors: a key promoter of cancer stem cell (CSC) resistance.
Cancer stem cells (CSCs) are highly tumorigenic cell types that reside within specific areas of tumor microenvironment (TME), and are endowed with self-renewal and resistance properties. Here, we aimed to discuss mechanisms involved in hypoxia-derived CSC resistance and targeting for effective cancer therapy. Preferential localization within hypoxic niches would help CSCs develop adaptive mechanisms, mediated through the modification of responses to various stressors and, as a result, show a more aggressive behavior. Hypoxia, in fact, serves as a multi-tasking strategy to nurture CSCs with this adaptive capacity, complexing targeted therapies.


Severe inframalleolar disease is an independent predictor of adverse limb outcomes after endovascular revascularization in chronic limb-threatening ischemia.
In the present study, we evaluated the effects of inframalleolar (IM) disease on the occurrence of major adverse limb events (MALE) in patients undergoing endovascular revascularization for chronic limb-threatening ischemia (CLTI). Patients who had undergone endovascular revascularization for CLTI between January 2015 and December 2019 at two university-affiliated hospitals were reviewed retrospectively. Patients with severe IM disease (pedal score of 2) were compared with those with mild to moderate IM disease (score of 0 or 1) using the Global Vascular Guidelines. The primary outcome was MALE (open revascularization, acute leg ischemia, major amputation). The secondary outcomes were mortality, reintervention, major adverse cardiac events, and perioperative complications ≤30 days after endovascular revascularization, primary limb-based patency, and the occurrence of any limb event (defined as any amputation, acute leg ischemia, or open revascularization). Kaplan-Meier estimates were used to compare the primary outcome, and the Cox proportion hazard model was used to assess the effects of IM disease. The study included 167 limbs in 149 patients (36% female; mean age, 74 ± 12 years). Severe IM disease was identified in 71 limbs (43%). No differences were found in the baseline characteristics, except for a higher prevalence of dyslipidemia in the patients with severe IM disease (66% vs 43%; P = .003). Most patients in both groups had had a WIfI (Wound, Ischemia, foot Infection) score of 4 (severe IM disease, 64%; vs mild to moderate IM disease, 57%; P = .462) and GLASS (global limb anatomic severity scale) III anatomy (severe IM disease, 54%; vs mild to moderate IM disease, 48%; P = .752). The Kaplan-Meier estimates showed that severe IM disease was associated with lower freedom from MALE (69% vs 82%; P = .026). The Cox proportion hazard regression model showed that severe IM disease was an independent predictor of increased MALE and amputation risk (hazard ratio, 1.715; 95% confidence interval, 1.015-2.896; P = .044) after adjusting for covariates. During follow-up, patients with severe IM disease had had mortality (27% vs 31%; P = .567) and reintervention (42% vs 38%; P = .608) similar to those for patients with mild to moderate IM disease. Primary limb-based patency was also similar (79% vs 84%; P = .593) at a mean follow-up of 3.8 ± 0.8 years. Severe IM disease was prevalent in 43% of limbs that had undergone endovascular revascularization for CLTI and was associated with lower freedom from MALE. Severe IM disease also independently increased the hazard of adverse limb outcomes and amputations in patients with CLTI by >70%, highlighting its importance as a measure of foot perfusion.


Primary structure of ten galactosides formed by transglycosylation during lactose hydrolysis by Bifidobacterium bifidum.
Oligosaccharides formed by a transgalactosylation reaction during lactose hydrolysis with Bifidobacterium bifidum were separated into eight fractions by gel-permeation chromatography and their structures studies determined by trimethylsilylation analysis, methylation analysis, f.a.b.-m.s., g.l.c.-m.s. and enzymic hydrolysis as beta-D-Galp-(1----3)-D-Glc, beta-D-Galp-(1----6)-D-Glc, beta-D-Galp-(1----6)-D-Gal, beta-D-Galp-(1----3)-beta-D-Galp-(1----4)-D-Glc, beta-D-Galp-(1----6)[beta-D-Galp-(1----4)]-D-Glc, beta-D-Galp-(1----2)[beta-D-Galp-(1----6)]-D-Glc, beta-D-Galp-(1----3)-beta-D-Galp-(1----3)-beta-D-Galp-(1----4)-D-Glc, beta-D-Galp-(1----3)-beta-D-Galp-(1----3)-beta-D-Galp-(1----3)-beta-D-Ga lp- (1----4)-D-Glc, beta-D-Galp-(1----3)-beta-D-Galp-(1----3)-beta-DGalp-(1----3)-beta -D-Galp-(1----3)-beta-D-Galp-(1----4)-D-Glc, and beta-D-Galp-(1----3)-beta-D-Galp-(1----3)-beta-D-Galp-(1----3)-beta-D-Ga lp-(1----3)-beta-D-G-alp-(1----3) beta-D-Galp-(1----4)-D-Glc.


Peripheral GABAA receptor signaling contributes to visceral hypersensitivity in a mouse model of colitis.
Pain is a common and debilitating symptom of inflammatory bowel disease (IBD). Based on evidence that peripheral GABAA receptor (GAR) inhibition plays an important role in establishing colonic afferent excitability and nociceptive threshold, we hypothesized that the increase in pain associated with IBD is due to, at least in part, a decrease in peripheral GAR-mediated inhibition. Acute colitis was induced with 5 days of dextran sodium sulfate (DSS, 3%) in the drinking water. Visceral sensitivity was assessed with the visceromotor response (VMR) evoked with balloon distention of the colon in control and DSS-treated mice before and after intracolonic administration of GAR agonist muscimol, the high-affinity GAR preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (THIP), the GAR positive allosteric modulator diazepam, or the GAR antagonists gabazine and bicuculline. Low concentrations of muscimol or THIP increased the VMR in DSS-treated mice but not in control mice. However, high concentrations of muscimol decreased the VMR in both control and DSS-treated mice. Diazepam decreased the VMR in both DSS-treated and control mice. By contrast, at a concentration of gabazine that blocks only low-affinity GAR, there was no effect on the VMR in either DSS-treated or control mice, but at concentrations of the antagonist that block low-affinity and high-affinity GAR, the VMR was increased in control mice and decreased in DSS-treated mice. Furthermore, bicuculline increased the VMR in control mice but decreased it in DSS-treated mice. These data suggest that activating of low-affinity GAR or blocking high-affinity GAR may be effective therapeutic strategies for the management of pain in IBD.


Expression of glycogenic genes in the oviduct of Chinese brown frog (Rana dybowskii) during pre-brumation.
The oviduct of Chinese brown frog (Rana dybowskii) displays seasonal morphological and functional changes, which expands specifically during pre-brumation. To uncover the molecular mechanism underlying this phenomenon, we firstly confirmed the increased weight and enlarged diameter of the oviduct in pre-brumation by morphological observation. Interestingly, the glycogen content in the oviduct increased significantly during pre-brumation, indicating Rana dybowskii stores energy in the oviduct before brumation. Transcriptome analysis further identified the differentially expressed genes in the synthesis and metabolism pathways of carbohydrates in the oviduct during pre-brumation. Based on that evidence, we focused on the mRNA and protein expression of glycogenic genes in the oviduct of Rana dybowskii. qPCR confirmed that the expression of glycolysis and glycogenesis-related genes were up-regulated while gluconeogenesis-related genes were down-regulated during pre-brumation. Western blot data showed that glucose transporter GLUT1 and glycogen synthesis-regulation proteins including GYS, and p-GSK-3β were highly expressed in the oviduct during pre-brumation. Moreover, immunohistochemical data showed that GLUT1, GYS, p-GYS, GSK-3β and p-GSK-3β were expressed regionally in the oviduct of Rana dybowskii. The data suggests that glycogen synthesis may be involved in the oviductal expansion of Rana dybowskii during the pre-brumation.


Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise.
In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.


Outcome of Canine Multicentric Lymphoma after Single or Divided Treatment with Cyclophosphamide in Multidrug Chemotherapy.
Cyclophosphamide is commonly used in combination chemotherapy to treat dogs with lymphoma. The metabolite of cyclophosphamide, acrolein, can irritate urinary bladder and cause sterile hemorrhagic cystitis. Dividing the administration of cyclophosphamide across multiple days may reduce the concentration of this metabolite in urinary bladder and reduce the possibility of cystitis. However, the impact of the therapeutic effect of this modification is not evaluated and compared to traditional single maximum-tolerated dose regimen. Seventy-two dogs with multicentric lymphoma received either bolus doses or divided doses of cyclophosphamide were included in this study. The incidence of hemorrhagic cystitis between 2 cyclophosphamide treatment groups was not significantly different (P = .357). There was no statistical difference in progression-free survival and survival time between 2 groups (P = .267 and P = .346). This modification of cyclophosphamide administration did not reduce the side effect of cystitis or affect remission and survival times in lymphoma dogs.


Spectral-domain Cirrus high-definition optical coherence tomography is better than time-domain Stratus optical coherence tomography for evaluation of macular pathologic features in uveitis.
To compare high-definition (HD) spectral-domain optical coherence tomography [SD-OCT] (Cirrus HD-OCT; Carl Zeiss, Dublin, California, USA) with time-domain optical coherence tomography [TD-OCT] (Stratus version 4; Carl Zeiss) for imaging macula in patients of uveitis. Interventional case series. Thirty consecutive patients (51 eyes) with uveitis of various causes with vitreous haze of 1+ or worse were treated in an institutional setting. All patients had their vitreous haze graded and OCT scans both on TD-OCT (Stratus) and SD-OCT (Cirrus). Information obtained from Cirrus OCT scans was compared with that obtained from Stratus OCT scans. Overall, for all grades of media clarity, the macula was interpreted as normal in 30 eyes (58.8%) on Stratus OCT and 26 eyes (50.9%) on Cirrus OCT and abnormal in 15 eyes (29.4%) on Stratus OCT and 24 eyes (47.0%) on Cirrus OCT, whereas poor scan quality deterred any interpretation in six eyes (10.0%) on Stratus OCT and only in one eye (1.8%) on Cirrus OCT. Additional information on Cirrus OCT could be obtained in nine (21.9%) of 41 eyes with grade 1+ vitreous haze, six (75%) of eight eyes with grade 2+ vitreous haze, and one eye (50%) with vitreous haze of 3+. Our preliminary results suggest that SD Cirrus HD-OCT has an advantage over TD Stratus OCT in uveitic eyes by providing better identification of normal and pathologic structure in patients with poor media clarity.


Comprehension priming as rational expectation for repetition: Evidence from syntactic processing.
Why do comprehenders process repeated stimuli more rapidly than novel stimuli? We consider an adaptive explanation for why such facilitation may be beneficial: priming is a consequence of expectation for repetition due to rational adaptation to the environment. If occurrences of a stimulus cluster in time, given one occurrence it is rational to expect a second occurrence closely following. Leveraging such knowledge may be particularly useful in online processing of language, where pervasive clustering may help comprehenders negotiate the considerable challenge of continual expectation update at multiple levels of linguistic structure and environmental variability. We test this account in the domain of structural priming in syntax, making use of the sentential complement-direct object (SC-DO) ambiguity. We first show that sentences containing SC continuations cluster in natural language, motivating an expectation for repetition of this structure. Second, we show that comprehenders are indeed sensitive to the syntactic clustering properties of their current environment. In a series of between-groups self-paced reading studies, we find that participants who are exposed to clusters of SC sentences subsequently process repetitions of SC structure more rapidly than participants who are exposed to the same number of SCs spaced in time, and attribute the difference to the learned degree of expectation for repetition. We model this behavior through Bayesian belief update, showing that (the optimal degree of) sensitivity to clustering properties of syntactic structures is indeed learnable through experience. Comprehension priming effects are thus consistent with rational expectation for repetition based on adaptation to the linguistic environment.


Lung Transplantation for Pulmonary Arterial Hypertension.
Even though patients with pulmonary arterial hypertension have multiple therapeutic options, the disease can be refractory despite appropriate management. In patients with end-stage pulmonary arterial hypertension, lung transplantation has the potential both to extend survival and improve health-related quality of life. Pulmonary arterial hypertension is the only major diagnostic indication for transplantation that is not a parenchymal pulmonary process, and thus the care of these patients is unique. This review focuses on the complexities of lung transplantation for patients with pulmonary arterial hypertension, presents the updated referral and listing criteria, and discusses the inequities in the organ allocation process that impact this disease group and the strategies to optimize outcomes for patients with pulmonary arterial hypertension who require lung transplantation. Lung transplantation is an effective and lifesaving therapy for patients with end-stage lung disease. Sadly, patients with pulmonary arterial hypertension face many challenges as it relates to transplantation including higher perioperative risks, inequities in the allocation system, and less favorable long-term outcomes. This review covers the complexities of transplantation in patients with pulmonary vascular disease.


Ureteroscopy.
From early 1982 to December 1985, 317 patients underwent 346 transurethral ureteroscopic procedures at our institution. For most patients the intramural ureter was dilated with balloon dilators and all procedures were performed under fluoroscopic control. The over-all success rate for lower ureteral stone removal was 95 per cent, which increased to 97 per cent for stones treated in 1984 and 1985. Ureteroscopy is useful for the evaluation of idiopathic gross hematuria, and for the diagnosis and treatment of ureteral and renal pelvic tumors. The over-all mean hospital stay was 4.9 days and the procedure has been a significant addition to our armamentarium.


Bioprospecting of marine diatoms Thalassiosira, Skeletonema and Chaetoceros for lipids and other value-added products.
Diatoms are a major storehouse of valuable fucoxanthin and polyunsaturated fatty acids, with enormous nutraceuticals and biofuel potential. Three marine diatom species isolated from the southern coast of India has been screened and their results show that highest biomass concentration and fucoxanthin yield was obtained in Chaetoceros sp. as 0.217 g L-1 and 0.403 mg L-1 respectively. Lipid % as dry cell weight was maximum in Thalassiosira sp. (52%) followed by Skeletonema sp. (44%) and Chaetoceros sp. (22%). However, protein and secondary metabolites content besides the total antioxidant activity was estimated highest in Skeletonema sp. Having strong inhibition zones of 18-20 mm against all the five strains of bacteria also highlights the highest antibacterial prospect in Skeletonema sp. This work manifests the plasticity of diatoms and may provide useful insights for further species-specific selection for large-scale production of eicosapentaenoic acid, docosahexaenoic acid, fucoxanthin and other metabolites with potential health benefits.


Countdown to compliance: privacy.
How far along the road to compliance with the HIPAA privacy regulation is your organization? This article tells you the steps you should be taking to get in compliance by the April 2003 deadline.


Information processing speed as a prognostic marker of physical impairment and progression in patients with multiple sclerosis.
Prediction of disability progression in patients with MS (pwMS) is challenging. So far, scarce evidence exists suggesting knowledge about how cognitive performance may potentially improve prediction of physical impairment and disability progression in MS. Therefore, we wanted to assess the prognostic value of cognitive performance regarding physical impairment and disability progression in pwMS. 85 patients (64% female; 60% relapse-remitting MS; mean age=36.78 ± 9.63 years) underwent clinical, neuropsychological (Brief Repeatable Battery for Neuropsychological Test (BRB-N)) and brain MRI (T1-weighted and T2-weighted FLAIR images) assessment at baseline and after an average of 7 years (SD=3.75) at follow-up. We assessed physical impairment and annualized disability progression (disability progression divided by follow-up duration) using the Expanded Disability Status Scale (EDSS). To compare patients with no or mild physical impairment (EDSS≤2.5) and patients with moderate to severe physical impairment (EDSS≥3.0), we used an EDSS score ≥3.0 as cut-off. Silent progression was defined by an EDSS worsening of at least 0.5 in the absence of relapses and inflammation in relapsing-remitting MS. In hierarchical regression models (method "STEPWISE", forward) performance in information processing speed was a significant and independent predictor of physical impairment (EDSS≥3.0) at follow-up (model R²=0.671, b=-1.46, OR=0.23, p=0.001) and annualized disability progression (adjusted model R²=0.257, β=-0.26, 95% CI: -0.066, -0.008, p=0.012), in addition to demographics (age, education, individual follow-up time), clinical (EDSS, disease duration, clinical phenotype, annualized-relapse-rate) and MRI measures (brain volumes and T2-lesion load). In a MANCOVA controlled for age, disease duration and individual follow-up time, worse baseline performance in information processing speed was found in patients with higher EDSS at follow-up (m=-1.91, SD=1.18, p<0.001) and silent progression (m=-2.19, SD=1.01, p=0.038). Performance in information processing speed might help to identify patients at risk for physical impairment. Therefore, neuropsychological assessment should be integrated in clinical standard care to support disease management in pwMS.


Cell-mediated lysis of heat-inactivated influenza virus-coated murine targets.
The involvement of inoculated virus antigens in the induction of target susceptibility to cytotoxic T lymphocyte (CTL)-mediated lysis was investigated using heat-inactivated influenza virus, PR8 strain, and various inhibitors in comparison to the cases for live or ultraviolet (u.v.)-irradiated influenza and Sendai viruses. Induction of target susceptibility with heated PR8 was not inhibited by cycloheximide and actinomycin D as in the case of u.v.-irradiated Sendai virus, whereas live virus and u.v.-irradiated PR8 were inhibited under conditions which suppress protein synthesis. Induction of target susceptibility with the live and inactivated PR8 tested was suppressed in the presence of chloroquine, contrary to the case of Sendai virus, and was dependent on the cleavage type of influenza virus haemagglutinin. These findings suggest that the viral target antigens recognized by CTL in heated PR8-coated targets came from inoculated virus proteins, whereas those in PR8-infected or u.v.-irradiated PR8-coated targets involved newly synthesized viral proteins. The former viral target antigens seem to be transferred or processed from the endosome, depending on low pH fusion in the endosomes into which they were engulfed. In this point, the induction of viral target antigens with heated PR8 was different from that induced by u.v.-inactivated Sendai virus. Targets made with heated PR8 were recognized by cross-reactive CTL over the HA subtype.


Can clinical colour vision tests be used to predict the results of the Farnsworth lantern test?
Clinicians usually do not have access to a lantern test when making an occupational assessment of the ability of a person with defective colour vision to recognise signal light colours: they must rely on the results of ordinary clinical tests. While all colour vision defectives fail the Holmes Wright Type B lantern test and most fail the Holmes Wright Type A lantern, 35% of colour vision defectives pass the Farnsworth lantern. Can clinical tests predict who will pass and fail the Farnsworth lantern? We find that a pass (less than two or more diametrical crossings) at the Farnsworth Panel D 15 Dichotomous test has a sensitivity of 0.67 and specificity of 0.94 in predicting a pass or fail at the Farnsworth lantern test: a Nagel range of > 10 has a sensitivity of 0.87 and a specificity of 0.57. We conclude that neither the D 15 nor the Nagel Anomaloscope matching range are satisfactory predictors of performance on the Farnsworth Lantern.


M0CRPC overview of management options.
Though prostate cancer usually responds to androgen deprivation therapy (ADT) in the beginning, the majority of prostate cancers will develop castration resistance over time. The androgen receptor (AR) pathway is often found to be activated in castration resistant prostate cancer (CRPC). Thus, AR signalling remains a therapeutic target upon the development of CRPC. The term M0CRPC is used when ADT leads to castration resistance and there are no metastases detectable by means of conventional imaging. Until recently, there was no therapeutic standard for this group of patients. With the PROSPER-, SPARTAN- and ARAMIS-studies three large placebo-controlled phase III trials have been published lately that showed a significant benefit in metastasis-free survival in men with M0CRPC and short PSA doubling time (PSADT). The efficacy data are very similar in these studies, meaning that the drugs' safety profiles, final analyses of overall survival and their availability will be more important to help clinicians decide which of these three drugs they use for their patients with M0CRPC.


Comparative repellency of 38 essential oils against mosquito bites.
The mosquito repellent activity of 38 essential oils from plants at three concentrations was screened against the mosquito Aedes aegypti under laboratory conditions using human subjects. On a volunteer's forearm, 0.1 mL of oil was applied per 30 cm2 of exposed skin. When the tested oils were applied at a 10% or 50% concentration, none of them prevented mosquito bites for as long as 2 h, but the undiluted oils of Cymbopogon nardus (citronella), Pogostemon cablin (patchuli), Syzygium aromaticum (clove) and Zanthoxylum limonella (Thai name: makaen) were the most effective and provided 2 h of complete repellency. From these initial results, three concentrations (10%, 50% and undiluted) of citronella, patchouli, clove and makaen were selected for repellency tests against Culex quinquefasciatus and Anopheles dirus. As expected, the undiluted oil showed the highest protection in each case. Clove oil gave the longest duration of 100% repellency (2-4 h) against all three species of mosquito.


Effect of glucagon-(1-21)-peptide on secretin-stimulated pancreatic exocrine secretion in anesthetized dogs.
The effects of glucagon-(1-21)-peptide on pancreatic exocrine secretion and plasma glucose levels were studied and compared with those of native glucagon in anesthetized dogs. Intravenous bolus administration of 1 nmol or 10 nmol/kg of glucagon-(1-21)-peptide evoked a significant inhibition of secretin-stimulated pancreatic juice secretion and protein output in a dose-dependent manner, as equimolar doses of glucagon did. Native glucagon induced an immediate and transient increase in pancreatic juice volume, which was followed by a significant inhibition. However, glucagon-(1-21)-peptide showed only the inhibitory action. Glucagon-(1-21)-peptide had no effect on plasma glucose levels even when a dose of 10 nmol/kg was given. The results suggest that the N-terminal amino-acid residues of glucagon play an important role in the inhibition of pancreatic exocrine secretion.


A retrospective analysis of the dynamic transmission routes of the COVID-19 in mainland China.
The fourth outbreak of the Coronaviruses, known as the COVID-19, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31-February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4-15, 2020. From February 16, 2020, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19, 2020. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19.


Metabolism of clofibric acid in zebrafish embryos (Danio rerio) as determined by liquid chromatography-high resolution-mass spectrometry.
The zebrafish embryo (ZFE) is increasingly used in ecotoxicology research but detailed knowledge of its metabolic potential is still limited. This study focuses on the xenobiotic metabolism of ZFE at different life-stages using the pharmaceutical compound clofibric acid as study compound. Liquid chromatography with quadrupole-time-of-flight mass spectrometry (LC-QToF-MS) is used to detect and to identify the transformation products (TPs). In screening experiments, a total of 18 TPs was detected and structure proposals were elaborated for 17 TPs, formed by phase I and phase II metabolism. Biotransformation of clofibric acid by the ZFE involves conjugation with sulfate or glucuronic acid, and, reported here for the first time, with carnitine, taurine, and aminomethanesulfonic acid. Further yet unknown cyclization products were identified using non-target screening that may represent a new detoxification pathway. Sulfate containing TPs occurred already after 3h of exposure (7hpf), and from 48h of exposure (52hpf) onwards, all TPs were detected. The detection of these TPs indicates the activity of phase I and phase II enzymes already at early life-stages. Additionally, the excretion of one TP into the exposure medium was observed. The results of this study outline the high metabolic potential of the ZFE with respect to the transformation of xenobiotics. Similarities but also differences to other test systems were observed. Biotransformation of test chemicals in toxicity testing with ZFE may therefore need further consideration.


Disruption of delayed memory for a sequence of spatial locations following CA1- or CA3-lesions of the dorsal hippocampus.
Axon-sparing neurotoxic lesions of CA1 or CA3 were produced in the dorsal hippocampus to test dissociative lesion effects on spatial working memory for sequential items. Rats were required to remember four different sections sequentially presented on a newly devised maze (i.e., Tulum maze) during a study phase. Each section was cued by a unique object that was specifically associated with each location within the section during the study phase. Following a 15-s delay and during the test phase, rats were required to revisit the location within a section randomly chosen among the previously visited sections in the absence of the cued object. Both CA1 and CA3 lesions similarly disrupted accurate relocation of a previously visited place. However, differential effects of the CA1 and CA3 lesions were observed in serial position curves. CA3-lesions disrupted performance for the first three serial positions, but did not disrupt performance for the last serial position (recency). In contrast, CA1-lesions disrupted performance for all serial positions. The results suggest that temporal separation of spatial memory may depend on the conjoint function of CA1 and CA3 of the hippocampus with a disruption of a spatial pattern completion process following CA3 lesions and a disruption of a temporal pattern separation process following a CA1 lesion.


Color mixture thresholds measured on a color television--a new method for analysis, classification and diagnosis of neuro-ophthalmic disease.
A color television display can be used to determine color and brightness discrimination thresholds using identical adaptation conditions and experimental technique. The color discrimination threshold is measured by using an equiluminous test spot--i.e. one which differs in color from the surrounding screen but has the same luminance. Because there is no brightness clue, the subject is forced to detect such a spot by using color discrimination. It is shown how color and brightness thresholds may be determined from threshold measurements of different color-mixtures even though it is not known beforehand which stimulus will be equiluminous for the subject. Results are shown for normal subjects, congenital color defectives and for two patients having optic nerve disease who show respectively non-selective and selective loss of color discrimination compared to brightness discrimination. Normal control data are presented, illustrating the effect of eccentricity, optical blur, viewing distance, pupil size and age. It is concluded that the technique is relatively insensitive to moderate variations in these factors and that it is more sensitive in detecting selective color loss than a spectral sensitivity technique which has been described previously.


Reconstruction of elbow extension.
The loss of elbow extension power is particularly disabling for the nonambulatory patient. Reconstruction of elbow extension can be performed by a deltoid to triceps transfer or by a biceps to triceps transfer provides the most satisfying reconstruction for patients. Although the overall time for rehabilitation can be lengthy, the functional gain is substantial, predictable, and easily appreciated by the patient. Furthermore, the risks to residual preoperative function are practically nil.


Medical imaging in pharmaceutical clinical trials: what radiologists should know.
The role of medical imaging in pharmaceutical clinical trials includes identification of likely responders; detection and diagnosis of lesions and evaluation of their severity; and therapy monitoring and follow-up. Nuclear imaging techniques such as PET can be used to monitor drug pharmacokinetics and distribution and study specific molecular endpoints. In assessing drug efficacy, imaging biomarkers and imaging surrogate endpoints can not only be more objective and faster to measure than clinical outcomes, but also allow small group sizes, quick results and good statistical power. In this article some basic principles of drug clinical development are explained. Study design, image reading and quantitative image processing in clinical trials with imaging components are discussed.


Mechanism of cleavage of apurinic sites by 9-aminoellipticine.
We have studied the kinetics of breakage of apurinic (AP) sites by the intercalating agent 9-aminoellipticine using fluorimetric methods with single (ss)- and double (ds)-stranded apurinic DNA. In order to understand the chemical process, high performance liquid chromatography was used to follow the reaction kinetics with the apurinic oligonucleotide model T(AP)T. The unstable intermediate, which is responsible for the beta-elimination step, is a Schiff base resulting from the interaction of the amino group of the aromatic amine with the aldehyde function of the deoxyribose moiety (AP site). Fluorescence occurs simultaneously with the breakage of both ss and ds DNA and of the oligonucleotide and arises from the formation of a conjugated double bond on the Schiff base through the beta-elimination reaction. In optimal conditions, the second order rate constant for the fluorescence build up is 15 x 10(3) min-1 M-1 for ds DNA and 0.105 x 10(3) min-1 M-1 for T(AP)T. The ability of 9-aminoellipticine to induce fluorescence and breakage of ss DNA and T(AP)T shows that intercalation is not essential for this reaction to occur. Nevertheless, the greater rate constant with DNA suggests that stacking is an important parameter for the reaction of the aromatic amine with the AP site.


The haem-copper oxygen reductase of Desulfovibrio vulgaris contains a dihaem cytochrome c in subunit II.
The genome of the sulphate reducing bacterium Desulfovibrio vulgaris Hildenborough, still considered a strict anaerobe, encodes two oxygen reductases of the bd and haem-copper types. The haem-copper oxygen reductase deduced amino acid sequence reveals that it is a Type A2 enzyme, which in its subunit II contains two c-type haem binding motifs. We have characterized the cytochrome c domain of subunit II and confirmed the binding of two haem groups, both with Met-His iron coordination. Hence, this enzyme constitutes the first example of a ccaa3 haem-copper oxygen reductase. The expression of D. vulgaris haem-copper oxygen reductase was found to be independent of the electron donor and acceptor source and is not altered by stress factors such as oxygen exposure, nitrite, nitrate, and iron; therefore the haem-copper oxygen reductase seems to be constitutive. The KCN sensitive oxygen reduction by D. vulgaris membranes demonstrated in this work indicates the presence of an active haem-copper oxygen reductase. D. vulgaris membranes perform oxygen reduction when accepting electrons from the monohaem cytochrome c553, thus revealing the first possible electron donor to the terminal oxygen reductase of D. vulgaris. The physiological implication of the presence of the oxygen reductase in this organism is discussed.


When Do Fathers Care? Mothers' Economic Contribution and Fathers' Involvement in Child Care.
Previous literature suggests a tenuous link between fathers' care of children and maternal employment and earnings. This study shows that the link is stronger when measures of caregiving capture fathers' increased responsibility for children. The analysis of time diary data from 6,572 married fathers and 7,376 married mothers with children under age 13 indicates that fathers (1) engage in more "solo" care of children when their wives are employed, (2) are more likely to do the kind of child care associated with responsibility for their children when their wives spend more time in the labor market, and (3) participate more in routine care when their wives contribute a greater share of the couple's earnings. In addition, the "father care" to "mother care" ratio rises when mothers contribute a greater share of household earnings.


Flexible opto-electronics enabled microfluidics systems with cloud connectivity for point-of-care micronutrient analysis.
In developing countries, the deployment of medical diagnostic technologies remains a challenge because of infrastructural limitations (e.g. refrigeration, electricity), and paucity of health professionals, distribution centers and transportation systems. Here we demonstrate the technical development and clinical testing of a novel electronics enabled microfluidic paper-based analytical device (EE-μPAD) for quantitative measurement of micronutrient concentrations in decentralized, resource-limited settings. The system performs immune-detection using paper-based microfluidics, instrumented with flexible electronics and optoelectronic sensors in a mechanically robust, ultrathin format comparable in size to a credit card. Autonomous self-calibration, plasma separation, flow monitoring, timing and data storage enable multiple devices to be run simultaneously. Measurements are wirelessly transferred to a mobile phone application that geo-tags the data and transmits it to a remote server for real time tracking of micronutrient deficiencies. Clinical tests of micronutrient levels from whole blood samples (n=95) show comparable sensitivity and specificity to ELISA-based tests. These results demonstrate instantaneous acquisition and global aggregation of diagnostics data using a fully integrated point of care system that will enable rapid and distributed surveillance of disease prevalence and geographical progression.


Significance of auditory brain stem response and gadolinium-enhanced magnetic resonance imaging for idiopathic sudden sensorineural hearing loss.
Previous studies tried to correlate prognosis and response to oral corticosteroids in patients with idiopathic sudden sensorineural hearing loss to such factors as the age of the patient, presence of vertigo, shape of the audiogram, or severity of the hearing loss. However, temporal bone histopathologic evidence shows that idiopathic sudden sensorineural hearing loss may be caused by cochleitis or cochlear nerve neuritis. Herein we report results of a retrospective study of 96 consecutive patients with idiopathic sudden sensorineural hearing loss who were evaluated with auditory brain stem responses and gadolinium-enhanced magnetic resonance imaging. Results of the auditory brain stem response and magnetic resonance imaging were correlated with hearing outcome. Follow-up was available for 65 patients: 14 with abnormal and 51 with normal auditory brain stem responses. The overall rate of hearing recovery or improvement was 65% in the normal auditory brain stem response group compared with 43% in the abnormal auditory brain stem response group (p = 0.07). Among the 38 patients treated with a tapering course of oral corticosteroids, the recovery or improvement rate was 83% for those with normal auditory brain stem responses and 56% for those with abnormal auditory brain stem responses (p < 0.05). Of the 27 patients who did not receive steroid therapy, the improvement rate was 41% in those with normal auditory brain stem responses and 20% in those with abnormal auditory brain stem responses (p = 0.09). Magnetic resonance imaging with gadolinium was obtained on all 14 patients with abnormal auditory brain stem responses but on none with normal auditory brain stem responses.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconfigurable dipole receive array for dynamic parallel imaging at ultra-high magnetic field.
To extend the concept of 3D dynamic parallel imaging, we developed a prototype of an electronically reconfigurable dipole array that provides sensitivity alteration along the dipole length. We developed a radiofrequency array coil consisting of eight reconfigurable elevated-end dipole antennas. The receive sensitivity profile of each dipole can be electronically shifted toward one or the other end by electrical shortening or lengthening the dipole arms using positive-intrinsic-negative-diode lump-element switching units. Based on the results of electromagnetic simulations, we built the prototype and tested it at 9.4 T on phantom and healthy volunteer. A modified 3D SENSE reconstruction was used, and geometry factor (g-factor) calculations were performed to assess the new array coil. Electromagnetic simulations showed that the new array coil was capable of alteration of its receive sensitivity profile along the dipole length. Electromagnetic and g-factor simulations showed closely agreeing predictions when compared to the measurements. The new dynamically reconfigurable dipole array provided significant improvement in geometry factor compared to static dipoles. We obtained up to 220% improvement for 3 × 2 (Ry × Rz ) acceleration compared to the static configuration case in terms of maximum g-factor and up to 54% in terms of mean g-factor for the same acceleration. We presented an 8-element prototype of a novel electronically reconfigurable dipole receive array that permits rapid sensitivity modulations along the dipole axes. Applying dynamic sensitivity modulation during image acquisition emulates two virtual rows of receive elements along the z-direction, and therefore improves parallel imaging performance for 3D acquisitions.


Intimate partner violence: A clinical update.
Intimate partner violence (IPV) is a significant public health issue associated with substantial morbidity and mortality. NPs are ideally positioned to screen for and intervene in IPV, thereby mitigating the health risks IPV carries for women, infants, and young children. Safety planning and appropriate referrals to community-based resources are critical components of addressing IPV.


Prevalence of root dilaceration in adult dental patients in Croatia.
To determine the prevalence and distribution of dilaceration in all tooth groups by using radiographs. The sample included 953 periapical intraoral radiographs and 488 panoramic radiographs from different caucasian patients. The ages of the patients ranged from 18-65 years. Dilaceration of the root was detected by measuring the degree of deviation from the long axis (deviation ł 90 degrees), and evaluating the "bull's eye" appearance. The prevalence of root dilaceration for each tooth-type was expressed in percentages. The teeth showing the highest prevalence of root dilaceration were mandibular third molars (24.1%), maxillary first molars (15.3%), second molars (11.4%) and third molars (8.1%). In the mandible, dilacerations were less common than in the maxilla. In the adult population examined in Croatia, dilaceration was most frequently found to affect posterior teeth.


Two proteinase activities in HCV polypeptide expressed in insect cells using baculovirus vector.
Processing of HCV viral precursor protein requires at least two viral proteinases, Cpro-1 and Cpro-2, in addition to cellular proteinases. The HCV polypeptide that covers the region for the two viral proteinase domains was expressed in insect cells using a baculovirus expression system. The two proteinase activities were demonstrated in the infected cells. The Cpro-1-dependent cleavage site was estimated from the amino acid sequence of the N-terminus of the processed product. Analyses of the susceptibilities of various mutants altered at position P1 and P1' of the putative cleavage site suggested that amino acid residues at these positions is not essential for recognition and cleavage by Cpro-1-dependent activity.


Angiographic demonstration of cervical extradural meningioma.
The diagnosis of a cervical extradural meningioma was made preoperatively on the basis of angiographic criteria. The entire extent of the tumor that partially encircled the dural sac could be demonstrated with regional spinal angiography.


Genetic estimates of correlation and causality between blood-based biomarkers and psychiatric disorders.
There is a long-standing interest in exploring the relationship between blood-based biomarkers and psychiatric disorders, despite their causal role being difficult to resolve in observational studies. In this study, we leverage genome-wide association study data for a large panel of heritable serum biochemical traits to refine our understanding of causal effect in biochemical-psychiatric trait pairings. We observed widespread positive and negative genetic correlation between psychiatric disorders and biochemical traits. Causal inference was then implemented to distinguish causation from correlation, with strong evidence that C-reactive protein (CRP) exerts a causal effect on psychiatric disorders. Notably, CRP demonstrated both protective and risk-increasing effects on different disorders. Multivariable models that conditioned CRP effects on interleukin-6 signaling and body mass index supported that the CRP-schizophrenia relationship was not driven by these factors. Collectively, these data suggest that there are shared pathways that influence both biochemical traits and psychiatric illness.


Abdominal pseudotumor caused by gastric displacement of the spleen: sonographic demonstration.
An infant with a factitious abdominal mass due to splenic displacement by the distended stomach is described. Two other cases of this phenomenon have been previously reported, both in infants and both diagnosed by radionuclide scans and plain radiographs. In our patient, diagnosis was made with ultrasound without the need for further studies.


Promising results of a new treatment in patients with bowel obstruction in colorectal surgery.
Bowel obstruction increases risk of emergency surgery and leads to suboptimal physical and nutritional condition. Preventing emergency surgery and prehabilitation might improve outcomes. This pilot study aimed to examine the effect of a multimodal obstruction protocol for bowel obstruction patients on the risk of emergency surgery and postoperative morbidity and mortality. All bowel obstruction patients treated according to the obstruction protocol in the period 2013-2017 were included in this uncontrolled observational cohort study. Benign and malignant causes of bowel obstruction were included. The protocol consisted of: 1. specific dietary adjustments to reduce prestenotic dilatation, 2. oral laxatives and 3. prehabilitation. Emergency surgery and postoperative morbidity and mortality rates were compared to known rates from the literature. Sixty-one patients were included: 44 (72%) were treated for colorectal cancer and 17 (28%) for Crohn's disease or diverticulitis. Four patients (7%) underwent emergency surgery. Primary anastomosis was constructed in 49 out of 57 elective patients (86%). Severe complications (Clavien-Dindo ≥ III) occurred in four patients (7%). No bowel perforation, anastomotic leakages or 30-day mortality was observed. These rates were much lower than rates reported in the literature after surgery for colorectal cancer (3% bowel perforation, 8% anastomotic leakage, 4% 30-day mortality, 15% severe complications) and benign disease (30-day mortality 17%, severe complications 7%). Using the obstruction protocol in patients with bowel obstruction reduced emergency surgery and postoperative morbidity and mortality in this pilot study. This protocol seems to be a viable and efficient alternative to emergency surgery.


Design, synthesis and evaluation of novel 2-butyl-4-chloroimidazole derived peptidomimetics as Angiotensin Converting Enzyme (ACE) inhibitors.
A series of novel 2-butyl-4-chloro-1-methylimidazole derived peptidomimetics were designed, synthesized and evaluated for their Angiotensin Converting Enzyme (ACE) inhibitor activity. 2-Butyl-4-chloro-1-methylimidazole-5-carboxylic acid 2 obtained after oxidation of respective carboxaldehyde 1, was condensed with various amino acid methyl esters 3a-k to give imidazole-amino acid conjugates 4a-k in very good yields. Ester hydrolysis of 4a-k with aqueous LiOH gave the desired peptidomimetics 5a-k. Screening all the new compounds 4a-k and 5a-k using ACE inhibition assay, resulted five compounds 4i, 4k, 5e, 5h and 5i as potent ACE inhibitors with IC50 of 0.647, 0.531, 1.12, 0.657 and 0.100μM with minimal toxicity. Among them, 5i emerged as most active ACE inhibitor with greater potency than marketed drugs Lisinopril, Ramipril and relatively equipotent to Benazepril, Quinapril and Enalapril.


The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation.
Various forms of fibrosis, comprising tissue thickening and scarring, are involved in 40% of deaths across the world. Since the discovery of scarless functional healing in fetuses prior to a certain stage of development, scientists have attempted to replicate scarless wound healing in adults with little success. While the extracellular matrix (ECM), fibroblasts, and inflammatory mediators have been historically investigated as separate branches of biology, it has become increasingly necessary to consider them as parts of a complex and tightly regulated system that becomes dysregulated in fibrosis. With this new paradigm, revisiting fetal scarless wound healing provides a unique opportunity to better understand how this highly regulated system operates mechanistically. In the following review, we navigate the four stages of wound healing (hemostasis, inflammation, repair, and remodeling) against the backdrop of adult versus fetal wound healing, while also exploring the relationships between the ECM, effector cells, and signaling molecules. We conclude by singling out recent findings that offer promising leads to alter the dynamics between the ECM, fibroblasts, and inflammation to promote scarless healing. One factor that promises to be significant is fibroblast heterogeneity and how certain fibroblast subpopulations might be predisposed to scarless healing. Altogether, reconsidering fetal wound healing by examining the interplay of the various factors contributing to fibrosis provides new research directions that will hopefully help us better understand and address fibroproliferative diseases, such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis.


[Circadian-induced change in the pharmacokinetic pattern exemplified on hexobarbital/Retrospective analysis of experimental data (author's transl)].
The present study dealt with data from a study to evaluate circadian influences on the pharmacokinetics of hexobarbital. It could be seen that the pharmacokinetic model changes from an open one-compartment model to an open two-compartment model in dependence of the time of application. The curve fitting to an open two-compartment model reached high correlations when the test substance was applied at 18 h. The pharmacokinetic parameters to be evaluated did not fit to literature data. After application of the substance at 10 h in the morning the curve fitting to an open one-compartment model correlated highly. The pharmacokinetic parameters at this time comparable with the known literature.


Interleukin-17A Promotes Proliferation and Osteogenic Differentiation of Human Ligamentum Flavum Cells Through Regulation of β-Catenin Signaling.
A basic experimental study. To elucidate the role and mechanism of interleukin (IL)-17A in thoracic ossification of the ligamentum flavum (TOLF). TOLF is characterized by the replacement of the thoracic ligamentum flavum with ossified tissue and is one of the leading causes of thoracic spinal stenosis. IL-17A is an important member of the IL-17 family that has received widespread attention for its key contributions to the regulation of bone metabolism and heterotopic ossification. However, it is unclear whether IL-17A is involved in TOLF. Cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine staining were performed to assess the proliferation of ligamentum flavum cells (LFCs). Alkaline phosphatase activity assay, Alizarin red staining, and protein level expression of osteogenic-related genes were used to evaluate the osteogenic differentiation potential of LFCs. The effect of IL-17A on the proliferation and osteogenic differentiation of LFCs was further assessed after silencing β-catenin by transfection with small interfering RNA. In addition, the possible source of IL-17A was further demonstrated by coculture assays of T helper 17 (Th17) cells with LFCs. Student t test was used for comparisons between groups, and the one-way analysis of variance, followed by the Tukey post hoc test, was used for comparison of more than two groups. IL-17A was elevated in TOLF tissue compared with normal ligamentum flavum. IL-17A stimulation promoted the proliferation and osteogenic differentiation of LFCs derived from patients with TOLF. We found that IL-17A promoted the proliferation and osteogenic differentiation of LFCs by regulating the β-catenin signaling. Coculture of Th17 cells with LFCs enhanced β-catenin signaling-mediated proliferation and osteogenic differentiation of LFCs. However, these effects were markedly attenuated after the neutralization of IL-17A. This is the first work we are aware of to highlight the importance of IL-17A in TOLF. IL-17A secreted by Th17 cells in the ligamentum flavum may be involved in the ossification of the microenvironment by regulating β-catenin signaling to promote the proliferation and osteogenic differentiation of LFCs.