A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses.
Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1 (P <1.68 × 10(-6)). Next generation DNA sequence analysis of 4 cases and 6 controls of gene exons within the region revealed a mutation in β-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) as the likely cause of hydrocephalus in Friesian horses. The nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous. A random sample of the Friesian horse population (n = 865) was tested for the mutation in a commercial laboratory. One-hundred and forty-seven horses were carrier and 718 horses were homozygous for the normal allele; the estimated allele frequency in the Friesian horse population is 0.085. Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* in B3GALNT2 (1:75,859,296-75,909,376) is concordant with hydrocephalus in Friesian horses. Application of a DNA test in the breeding programme will reduce the losses caused by hydrocephalus in the Friesian horse population.


Component analysis of fluorescence spectra of thiol DAB dendrimer/ZnSe-PEA nanoparticles.
The fluorescence spectroscopy technique is an accurate method and has great utility in the interpretation of complex systems based on several emission bands. An interpretation of the system requires determination of the number, positions and intensities of the spectral components. In this work, the emission spectra of the synthesized ZnSe complex coated with O-phosphorylethanolamine (ZnSe-PEA), both with and without thiol DAB dendrimer generation 5 (S-DAB G5), were analyzed using a combination of asymmetric (log-normal) and symmetric (Gaussian) models. The method applied for the deconvolution of fluorescence spectra has proven to be very sensitive for observing the stability of the ZnSe-PEA complex after binding with S-DAB. The ZnSe-PEA emission spectrum contains two components. The positions of the emission maxima of these two components are not significantly affected by the presence of S-DAB G5 in the complex, which revealed the presence of a stable complex at a pH of 7. By applying the spectral deconvolution method, strong evidence was obtained that suggested that the ZnSe-PEA complex is stable after complexation with S-DAB G5.


Socio-economic analysis of the risk management of hexabromocyclododecane (HBCD) in China in the context of the Stockholm Convention.
Socio-economic analysis (SEA) plays an important role in decision-making on risk management actions for certain chemicals under Multilateral Environmental Agreements (MEAs) in developing countries. This paper showed the first holistic and quantitative SEA case study on that by developing a country-specific SEA framwork and methodologies and applying the case of HBCD phase-out in China under the Stockholm Convention on Persistent Organic Pollutants (POPs). The study indicates that, under the possible scenarios of 10 years and 5 years , the economic costs of HBCD phase-out in China would be between 9.032 and 19.021 billion RMB. Although the total economic costs seems to be significant, it would only have a marginal impact on the house building industry with a likely cost increase by about 0.07‰-0.14‰. Meanwhile, the HBCD phase-out may render significant environmental and health benefits, including about 23-29 tons of HBCD release prevented to the environment, 1.142-1.469 million tons of potentially HBCD contained hazardous wastes avoided, along with significant reduction from 58% up to almost 100% in local environmental concentrations of HBCD, and about 0.0996-0.128 million workers at risk avoided and at least 3.067-4.033 billion RMB of the health care savings. While the scenario of phasing out HBCD over 10 years would be less costly than the scenario of that over 5 years, the later scenario suggested much greater environmental and health benefits for China.


Roles of paxillin family members in adhesion and ECM degradation coupling at invadosomes.
Invadosomes are acto-adhesive structures able to both bind the extracellular matrix (ECM) and digest it. Paxillin family members-paxillin, Hic-5, and leupaxin-are implicated in mechanosensing and turnover of adhesion sites, but the contribution of each paxillin family protein to invadosome activities is unclear. We use genetic approaches to show that paxillin and Hic-5 have both redundant and distinctive functions in invadosome formation. The essential function of paxillin-like activity is based on the coordinated activity of LD motifs and LIM domains, which support invadosome assembly and morphology, respectively. However, paxillin preferentially regulates invadosome assembly, whereas Hic-5 regulates the coupling between ECM degradation and acto-adhesive functions. Mass spectrometry analysis revealed new partners that are important for paxillin and Hic-5 specificities: paxillin regulates the acto-adhesive machinery through janus kinase 1 (JAK1), whereas Hic-5 controls ECM degradation via IQGAP1. Integrating the redundancy and specificities of paxillin and Hic-5 in a functional complex provides insights into the coupling between the acto-adhesive and ECM-degradative machineries in invadosomes.


[Physiology and biochemistry of streptomycetes. XIII. Biosynthesis of paromomycin by Streptomyces albus var. metamycinus nov. var. supplied with 14C-glucose, 14C-glucosamine, 14C-2-desoxystreptamine and 14C-ribose].
Distribution of radioactivity in paromomycin ascertained after application of 14C-D-glucose, 14C-D-glucosamine, 14C-2-deoxystreptamine, respectively, 14C-D-ribose is taken as basis for a biosynthesis scheme: While ribose bound in the antibiotic originates from glucose by oxidation and following decarboxylation, glucosamine is formed via fructose-6-phosphate. Paromose I arises from glucosamine, but not the cyclohexan derivative 2-deoxystreptamine, whose biosynthesis pathway is directly branching off glucose.


Regional differences and driving forces of ecosystem health in Yangtze River Basin, China.
Ecosystem health in the Yangtze River basin (YRB) shows significant regional differences. Analysis of regional differences and drivers of ecosystem health in YRB is of practical significance for sustainable basin ecological management. However, existing studies lack research on regional differences and driving forces of ecosystem health, especially in big basin regions. Based on multi-source data, this study adopted spatial statistics and distribution dynamics models to quantitatively analyze the regional differences of ecosystem health in the YRB during 2000-2020 and employed the spatial panel model to reveal the driving forces of ecosystem health in the YRB. The ecosystem health index of the upper, middle, and lower reaches of YRB and the entire basin in 2020 was 0.753, 0.781, 0.637, and 0.742, respectively, while they all decreased during 2000-2020. Regional differences in YRB ecosystem health increased during 2000-2020. From the perspective of dynamic evolution, low-level and high-level ecosystem health units evolved to high-level, while medium-high-level ecosystem health units evolved to low-level. High-high (accounting for 30.372% in 2020) and low-low (accounting for 13.533% in 2020) were the main cluster types. Regression result showed that urbanization was the main reason for ecosystem health deterioration. The findings can provide enlightenment to further understand the regional differences of ecosystem health in YRB and provide theoretical reference for the coordinated management of ecosystem at macro-level and the differential regulation of local ecosystem at micro-level in the basin region.


Why the resistance to statistical innovations? A comment on Sharpe (2013).
Sharpe's (2013) article considered reasons for the apparent resistance of substantive researchers to the adoption of newer statistical methods recommended by quantitative methodologists, and possible ways to reduce that resistance, focusing on improved communication. The important point that Sharpe missed, however, is that because research methods vary radically from one subarea of psychology to another, a particular statistical innovation may be much better suited to some subareas than others. Although there may be some psychological or logistical explanations that account for resistance to innovation in general, to fully understand the resistance to any particular innovation, it is necessary to consider how that innovation impacts specific subareas of psychology. In this comment, I focus on the movement to replace null hypothesis significance testing (NHST) with reports of effect sizes and/or confidence intervals, and consider its possible impact on research in which only the direction of the effect is meaningful, and there is no basis for predicting specific effect sizes (and very large samples are rarely used). There are numerous examples of these studies in social psychology, for instance, such as those that deal with priming effects. I use a study in support of terror management theory as my main example. I conclude that the degree to which statistical reformers have overgeneralized their criticisms of NHST, and have failed to tailor their recommendations to different types of research, may explain some of the resistance to abandoning NHST. Finally, I offer suggestions for improved communication to supplement those presented by Sharpe. (PsycINFO Database Record


The impact of conductive hearing loss on balance.
Balance is a complex process involving the coordinated activities of multiple sensory, motor and biomechanical components. Balance function may be disturbed in subjects suffering from hearing loss but the impairment has been attributed to the pathology underlying the hearing loss. The purpose of the study was to investigate the possible interference of simulated conductive hearing loss with the ability to maintain postural balance. Twenty normal-hearing subjects, 20-30 years old, underwent the computerised dynamic posturography test battery before and after plugging their external ear canals with earplugs, thus simulating a 40dB conductive hearing loss. Eighteen females and two males were tested before and after plugging their ear canals. Average CHL was 40 ± 4.9dB. The composite equilibrium score was significantly diminished after plugging the ears with an average sway score of 73.5% (P < .05, T = 2.27). The fourth test condition was specifically affected with an average sway score of 72.85% with earplugs (P < .05, T = 2.37). Conductive hearing loss has a negative effect on balance. This can be theoretically explained by the association between hearing loss and saccular dysfunction.


Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS).
The immunopathogenesis of leukopenia and thrombocytopenia in patients with severe acute respiratory syndrome (SARS) is unclear. In order to explore the leukopenia mechanism, we studied 15 SARS patients who were previously healthy, and 15 age-matched normal controls in a paired design. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble Fas ligand (sFasL) in plasma were measured by ELISA, and intracellular activated caspase-3 fragment in different leukocytes was determined by flow cytometry. Patients with SARS had significantly lower lymphocyte and platelet counts and significantly higher sVCAM-1 and sFasL levels compared to healthy controls. sVCAM-1 levels correlated negatively with total leukocytes and platelet counts, but positively with plasma sFasL levels. Intracellular cleaved caspase-3 expression was also significantly higher in lymphocytes from SARS patients in acute phase than in convalescent stage. Lymphopenia and thrombocytopenia in SARS patients may be caused, in part, by enhanced vascular sequestration associated with increased sVCAM-1 levels. However, lymphopenia may be due to enhanced cell death. Inhibition of cell adhesion and caspase-3 activation could, therefore, have prevented SARS patients from developing thrombocytopenia and lymphopenia.


The effect of time since measles vaccination and age at first dose on measles vaccine effectiveness - A systematic review.
In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies.


Impact of residual contamination on the biofunctional properties of purified alginates used for cell encapsulation.
Alginate is frequently used for cell encapsulation, but its biocompatibility is neither optimal nor reproducible. Purifying the alginate is critical for achieving a suitable biocompatibility. However, published purification methods vary in efficiency and may induce changes in polymer biofunctionality. Applying X-ray photoelectron spectroscopy, we showed that commercial alginates, purified by in-house and industrial methods, contained elemental impurities that contributed 0.41-1.73% of their atomic composition. Residual contaminants were identified to be proteins (nitrogen/COOH), endotoxins (phosphorus), and fucoidans (sulphur). Studies using attenuated total reflectance Fourier transform infrared spectroscopy suggested that trace contamination did not alter the alginate molecular structure. Alginate hydrophilicity increased by 19-40% after purification, in correlation with a reduction in protein and polyphenol content. Solution viscosity of the alginate increased by 28-108% after purification, in correlation with a reduction in protein content. These results demonstrate that commercial alginates contain potentially immunogenic contaminants that are not completely eliminated by current purification methods. Moreover, these contaminants alter the functional properties of the alginate in a manner that may compromise biocompatibility: Hydrophilicity may affect protein adsorption and solution viscosity influences the morphology of alginate-based microcapsules. These findings highlight the need to improve and better control alginate purity to ensure a reproducible biofunctionality and optimal biocompatibility of alginate and microcapsules.


Saw palmetto extract enhances erectile responses by inhibition of phosphodiesterase 5 activity and increase in inducible nitric oxide synthase messenger ribonucleic acid expression in rat and rabbit corpus cavernosum.
To evaluate whether saw palmetto extract (SPE) relaxes corpus cavernosum and explore the underlying mechanisms. Forty Sprague-Dawley rats and 30 New Zealand rabbits were randomly allocated into 3 SPE-treated groups (low-, middle-, and high-dose) and 1 saline-treated control group. SPE was administered intragastrically for 7 consecutive days. Another 23 rats treated with sildenafil were used to appraise the erectile response to electrical stimulation of nerves in the corpus cavernosum. The erectile functions of rats and rabbits were evaluated 24 hours after the last SPE administration or 15 minutes after intragastric sildenafil. Outcome measures included corpus cavernosum electrical activity recording, phosphodiesterase 5 (PDE5) activity detected by the colorimetric quantitative method, and messenger ribonucleic acid (mRNA) expression level for PDE5 and inducible nitric oxide synthase (iNOS) determined using real-time polymerase chain reaction. In the SPE-treated animals, the relaxant response to electrical stimulation of nerves in the corpus cavernosum, reflected by the amplitude of the electrical activity within the cavernosum, was significantly and dose-dependently augmented. Similar effects were observed in the sildenafil-treated rats. PDE5 activity in rat and rabbit corpus cavernosum tissues was significantly and dose-dependently inhibited in SPE-treated animals, whereas the iNOS mRNA level increased compared with the saline group. PDE5 mRNA, however, was only significantly enhanced in the rats treated with the middle dose of SPE. The results suggest that SPE may have potential application value for the prevention or treatment of erectile dysfunction through an increase in iNOS mRNA expression and inhibition of PDE5 activity in corpus cavernosum smooth muscles.


Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice.
Recent studies have discovered a strong link between physical exercise and the prevention of neuro-degenerative symptoms, especially in elderly subjects, nonetheless, the exact underlying mechanism remains unclear. In this study, we hypothesized that aerobic exercise training may have a protective effect on myelin sheath in aged mice by regulating the ROCK signal pathway, which is considered as a crucial mechanism for decreasing apoptosis and promoting regeneration. Briefly, C57/BL aged mice underwent an exercise training (5 days/week, lasting 6 weeks). Memory and cognitive impairment were examined using Novel object recognition (NOR) test and Morris water maze test (MWM). Demyelination was explored using Luxol fast blue staining and transmission electron microscopy in the corpus callosum (CC), and the expression of ROCK and apoptotic protein were analyzed via western blot. We demonstrated the impairment of memory and cognitive and the decrease of myelin sheath thickness in aged mice. In addition, severe demyelination was observed in aged mice, accompanied with increased expression of RhoA, ROCK, ATF3, and Caspase 3, and reduced expression of MBP, Olig2, and NG2. Aerobic exercise training improved behavioral functions, increased the expression of MBP and myelin sheath thickness, reduced apoptosis and promoted myelination. To sum up, our data indicate that aerobic exercise training protects demyelination from aging-related white matter injury, which is associated with the up-regulation of ROCK signal pathway.


Age-dependent changes in brain glycine concentration and strychnine-induced seizures in the rat.
Glycine levels and receptor binding were measured in the medulla and spinal cord of 2-month, 10-month, and 24-month-old Fischer 344 rats. The behavioral response to the administration of the glycine antagonist, strychnine, was also evaluated in 2- and 24-month-old animals to investigate the relevance of these parameters to the susceptibility to seizures. Significant reductions in glycine in both the spinal cord and medulla occurred from 2 to 24 months of age. The glycine precursors, serine and threonine, were decreased only in the spinal cord. [3H]Strychnine binding was also decreased by 38% and 34% in the medulla and spinal cord, respectively, of 24-month-old rats compared to 2-month-olds. [3H]GABA binding was similarly reduced while no age-related changes in [3H]diazepam binding in the spinal cord were detected. Comparison of 2- and 24-month-old animals after systemic injection of 1.75 mg/kg strychnine showed that senescent animals have a higher incidence of seizures and mortality compared to young animals. Decreases in glycinergic neurotransmission may lower strychnine seizure threshold in the aged animal.


Hypertension in thoracic transplant recipients.
There are many mechanisms underlying the hypertension which occurs after thoracic transplantation. Previous disease, effects of cyclosporin, tacrolimus and steroid immunosuppression and cardiac denervation are major contributory factors. Abnormal sodium and water balance is an important common mediating factor. A new approach is clearly needed for classifying the severity of hypertension in these patients taking into account day-night variation and total blood pressure (BP) load. This would allow improved strategies for investigation and treatment. The evidence suggests that ambulatory BP measurements should be included in the assessment of initial severity of post-transplant hypertension as well as response to treatment. Further studies are needed to look at the effects of raised clinic and 24-h ambulatory BP and its treatment on longer term morbidity and mortality in thoracic transplant patients.


Oral health literacy: the new imperative to better oral health.
Effective communication with patients is the cornerstone of quality dental care and oral health outcomes. Oral health literacy skills are critical to empowering individuals' ability to improve their oral health. A large part of the American public has low health literacy skills. Low health literacy contributes to disease and is costly. Being able to understand health information and how to obtain services is critical to oral health management. The communication skills of the dental team are pivotal to increasing oral health literacy skills of Americans.


Prevention of bronchial hyperreactivity in children.
Hyperresponsiveness of the bronchi is defined as an excessive reaction of bronchial mucosa to irritants that do no harm to a healthy mucosa. Measures to prevent bronchial hyperreactivity in children with asthma and other diseases remain rather ineffective at present. Though progress has been made in some areas.


Bedbugs.
Though most people have a sense of revulsion at the mention of the word 'bedbugs' they are actually quite fascinating. Klaus Reinhardt offers insights into these much-maligned creatures.


Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway.
Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg-1· d-1, iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1-100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway.


[Effect of disseminated necrotic heart lesions on incorporation of radioactive precursors into the RNA of the inner membranes of rat myocardial mitochondria].
The authors studied the role played by the internal membranes of the myocardial mitochondria of rats as the site of radioactive precursors incorporation into the mitochondrial RNA. As revealed, kinetics of the changes of the specific RNA activity of the internal membranes of the myocardial mitochondrial in vivo and in vitro differed. Necrosis of the myocardium induced both in vivo and in vitro significant changes in the specific activity of the RNA of the mitochondrial membranes.


Marital interaction coding system: revision and empirical evaluation.
Given the vast amount of codeable information in marital interactions, observational coding systems must emphasize particular classes of behavior. The most widely used marital coding scheme, the Marital Interaction Coding System (MICS), like many older behavioral coding systems, emphasizes verbal content over affect. Changes made to the MICS between versions III and IV are described; they were intended to increase the system's use of coded affect and to decrease autodependence in sequential analysis. We used an archival data set of 994 couples' videotaped conflict negotiations coded with the MICS. As intended, the MICS-IV, relative to the MICS-III, was found to have the advantage of capturing more non-verbal affect expressed during marital interactions, which resulted in stronger interactional contingencies (e.g. Wife Blame-->Husband Blame, Husband Facilitation-->Wife Facilitation). The MICS-IV also yielded significantly lower levels of spurious autodependence.


Angiogenesis inhibitors derived from thalidomide.
5-Hydroxy-2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33: 10), which was obtained during our previous structural development studies on thalidomide, was revealed to possess potent anti-angiogenic activity in a human umbilical vein endothelial cell (HUVEC) assay. Thalidomide (1) and its metabolite, 5-hydroxythalidomide (5-HT: 2), which possesses a hydroxyl group at the position corresponding to that of 5HPP-33, as well as IMiDs (immunomodulatory derivatives of thalidomide: 3 and 5), also showed weak or moderate activity in the same assay.


Lessons from Wolfram Syndrome: Initiation of DDAVP Therapy Causes Renal Salt Wasting Due to Elevated ANP/BNP Levels, Rescued by Fludrocortisone Treatment.
Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and "B" had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2-4 fold elevated. Fludrocortisone 100-200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation.


Oxygen-dependent electron transport and protection from photoinhibition in leaves of tropical tree species.
The roles of photorespiration and the Mehlerperoxidase pathway in sustaining electron transport and protection from photoinhibition were studied in outer canopy leaves of two species of tropical trees: the drought-deciduous Pseudobombax septenatum (Jacq.) Dug. and the evergreen Ficus insipida Willd. Ficus had a higher photosynthetic capacity than Pseudobombax and also a greater capacity for light-dependent electron transport under photorespiratory conditions (in the absence of CO2). As a consequence, in the absence of CO2, Ficus was able to maintain a largely oxidized electron-transport chain at higher photon flux densities than Pseudobombax. Under the same light conditions, photoinhibition (reduction in Fv/Fm) was always greater in Pseudobombax than Ficus, was increased when leaves were exposed to 2% O2 in nitrogen compared to 21% O2 in CO2-free air, but was not increased by the absence of CO2. Rates of electron transport due to the Mehler-peroxidase pathway (assessed in 2% O2 in nitrogen) ranged between 16-40 μmol · m-2·s-1 in both species. As the dry season approached and Pseudobombax neared leaf senescence there was a decline in the capacity for photorespiratory flux to maintain electron transport in Pseudobombax, but not in Ficus. Ratios of light-dependent electron transport to net CO2 fixation for Pseudobombax, Ficus and two other species in the field, Luehea seemannii Tr. & Planch, and Didymopanax morototoni (Aubl.) Dec. & Planch., ranged from 6.2 (Ficus) to 16.7 (Pseudobombax). High in-situ rates of photorespiration combined with the decreased capacity of Pseudobombax for photorespiratory flux as the dry season approached indicates a decreased capacity to protect against photooxidative damage. This may contribute to the promotion of leaf senescence in Pseudobombax during the transition from wet to dry season.


Etiology of breast carcinoma: no apparent role for papillomavirus types 6/11/16/18.
A recent study has shown that human papillomavirus (HPV) types 16 and 18 can immortalize normal breast epithelium, and raised the possibility that HPV may be etiologically related to some cases of breast cancer. In order to investigate this possibility, we performed polymerase chain reaction (PCR) assays for HPV types 6, 11, 16 and 18 in 15 papillomas, 15 papillary carcinomas, and 13 infiltrating ductal carcinomas of the breast. No HPV-related DNA sequences were identified by Southern blotting of the PCR products. It therefore seems unlikely that a significant percentage of human breast carcinomas is etiologically related to infection with one of these HPV types.


Oral lichenoid dysplasia: a clinicopathologic analysis.
Three women had a diagnosis of oral lichen planus (OLP), which was made on the basis of clinical and histologic features. All three had persistent burning pain associated with large mucosal lesions. Changes in the color (red, red and white, white), configuration, and severity of the lesions were unpredictable and did not correlate well with topical corticosteroid therapy. Only one patient used tobacco (cigarettes)--this patient had recurrent oral candidiasis and was receiving multiple medications. One of the two nonsmokers was a denture wearer with a single episode of candidiasis. After 63, 32, and 56 (mean 50) months, carcinoma developed in all three. In retrospect, the initial biopsy specimens of two patients exhibited lichenoid dysplasia, whereas that of the third showed only lichenoid mucositis. Although speckled erythroplakia was the earliest clinical sign of a classic, nonregressing premalignant lesion, it already signaled the presence of invasive carcinoma. Some early epithelial dysplasias appear to have a robust inflammatory/immunologic response to the antigenically (but as yet not histologically) altered dysplastic epithelium and a high probability of at least temporary resolution. Mucosal erythema of obscure origin displaying spontaneous, usually temporary, partial to complete regression may be common to both purely inflammatory conditions like lichen planus and early epithelial dysplasia. We contend that some, if not most, cases of apparent malignant transformation of OLP likely represent red and white lesions that were dysplastic from their inception but that mimic OLP both clinically and histologically.


Compound implant to project the nasal tip.
Use of a compound implant to project the nasal tip in cases of thick skin, a depressed or slightly descending tip, and a minimal bony hump is reported. This implant gives shape and projection, is easy to obtain, and is well tolerated by the organism. It is made of a strip of septal cartilage or silastic; the anterior end is covered by a portion of alar cartilage. There is a low percentage of complications with this technique.


Field measurements and modeling of dilution in the wake of a US navy frigate.
A field measurement and computer modeling effort was made to assess the dilution field of pulped waste materials discharged into the wake of a US Navy frigate. Pulped paper and fluorescein dye were discharged from the frigate's pulper at known rates. The subsequent particle and dye concentration field was then measured throughout the wake by a following vessel using multiple independent measures. Minimum dilution of the pulped paper reached 3.2 x 10(5) within 1900 m behind the frigate, or about 8 min after discharge. Independent measures typically agreed within 25% of one another and within 20% of model predictions. Minimum dilution of dye reached 2.3 x 10(5) at a down-wake distance of approximately 3500 m, or roughly 15 min. Comparison to model measurements were again within 20%. The field test was not only successful at characterizing wake dilution under one set of at-sea conditions, but was successful at validating the computer model used for assessing a wide range of ships and conditions.


Wide sugar substrate specificity of galactokinase from Streptococcus pneumoniae TIGR4.
Galactokinases (GALK) have attracted significant research attention for their potential application in the enzymatic synthesis of unique sugar phosphates. The galactokinase (GalKSpe4) cloned from Streptococcus pneumoniae TIGR4 had a temperature optimum of 45°C, and a pH optimum of 8.0. The substrate specificity and kinetics studies revealed that GalKSpe4 had moderate activity toward glucose, in contrast with very low or no activity observed in other previously reported GALKs. Most interestingly, GalKSpe4 exhibited activity for GalNAc, which had never been recorded in other GALKs found by now. This is the first time to report that bacterial GALK can recognize GalNAc.


Alcohol seeking in C57BL/6 mice induced by conditioned cues and contexts in the extinction-reinstatement model.
We have recently shown that the alcohol self-administration context can reinstate extinguished responding for alcohol when that extinction occurs in a different context [Burattini, C., Gill, T. M., Aicardi, G., & Janak, P. H. (2006)]. The ethanol self-administration context as a reinstatement cue: acute effects of naltrexone. Neuroscience, in press; Zironi, I., Burattini, C., Aicardi, G., & Janak, P. H. (2006). Context is a trigger for relapse to alcohol. Behav Brain Res 167, 150-155). Here, we test whether the C57BL/6 mice will also show context-induced reinstatement for alcohol, and whether presentation of an alcohol-associated cue will alter the observed responding. Male C57BL/6 mice were trained to lever press on a fixed ratio-3 schedule for a 10% ethanol solution in a context made distinctive using visual, tactile, and olfactory stimuli. Each ethanol delivery was paired with a compound tone-light stimulus. After training, extinction sessions were given in a distinct context, comprised of different visual, tactile, and olfactory stimuli; the compound cue and the alcohol were not available during these sessions. In Experiment 1, after response extinction, subjects were tested by placement into both the alcohol self-administration context and, on a subsequent test, by response-contingent presentation of the cue following placement into the alcohol self-administration context. In Experiment 2, after response extinction, subjects were tested in both of these conditions, with the addition of a test of the effects of response-contingent presentation of the cue in the extinction context. The results indicate that the alcohol self-administration context produces a mild increase in responding at the alcohol lever, and that presentation of the alcohol-associated cue in the alcohol context, but not the extinction context, strongly increases responding on the alcohol lever. These findings suggest that the power of an alcohol-associated cue can be modulated by the context. The observed effects of alcohol contexts and cues on alcohol-seeking behavior in the C57BL/6 mouse suggest that this reinstatement model may be useful for understanding the neurobiological and genetic mechanisms of relapse triggered by conditioned environmental stimuli.


Physiological and health consequences of social status in zebrafish (Danio rerio).
Social status affects access to food, mates and shelter and has consequences for the physiology of individuals and their health status. In the zebrafish (Danio rerio), an emerging model for studies into animal behavior, the possible consequences of social hierarchy to an individual's physiology and health are unknown. To address this, in this species we assessed the effects of social interaction (for periods of 1-5days) on growth, stress, immune function and reproductive condition. Wide-ranging differences in physiology occurred between the social ranks, some of which were sex-related and time-dependent. In both sexes, dominant fish were larger than subordinates and dominant males had a higher growth rate during the trials. Subordinates had higher plasma cortisol and in males higher telencephalic corticotrophin-releasing hormone, neuropeptide y and glucocorticoid receptor gene expression. Splenic cytokine expression suggested differences in immune status between ranks in both sexes and hematocrit was elevated in subordinate males. In both sexes, dominants and subordinates differed in the expression of genes for various gonadal sex steroid receptors and steroidogenic enzymes and in dominant females the ovary was larger relative to body mass compared with in subordinates. Dominant males had higher plasma 11-ketotestosterone than subordinates and there was an increase in the number of spermatids in their testes over the duration of the study that was not seen in subordinate males. The wide-ranging physiological differences seen between dominant and subordinate zebrafish as a consequence of their social status suggest negative health impacts for subordinates after prolonged durations in those hierarchies.


Caregiving burden and positive aspects of caregiving in schizophrenia: Mediating roles of hope and social support.
Caring for an ill relative with schizophrenia can lead to both negative and positive experiences. The study aimed to determine the relationship between caregiving burden and positive caregiving experiences and evaluate the roles of hope and social support as possible mediators in this relationship. This study included 344 Chinese family caregivers of adults with schizophrenia. Instruments included Positive Aspects of Caregiving, Herth Hope Index, Caregiver Burden Inventory, and Multidimensional Scale of Perceived Social Support. Data was analysed by Mann-Whitney U tests, Kruskal-Wallis H tests, Spearman correlation, and a serial mediation model. Results showed that hope and social support separately and serially mediated the relationship between caregiving burden and positive caregiving experiences. The mediation effect of hope was stronger than that of social support and their serial mediation effect. Increasing hope and social support of family caregivers may alleviate caregiving burden and improve positive caregiving experiences.


Simultaneous selection for grain yield and protein content in genomics-assisted wheat breeding.
Large genetic improvement can be achieved by simultaneous genomic selection for grain yield and protein content when combining different breeding strategies in the form of selection indices. Genomic selection has been implemented in many national and international breeding programmes in recent years. Numerous studies have shown the potential of this new breeding tool; few have, however, taken the simultaneous selection for multiple traits into account that is though common practice in breeding programmes. The simultaneous improvement in grain yield and protein content is thereby a major challenge in wheat breeding due to a severe negative trade-off. Accordingly, the potential and limits of multi-trait selection for this particular trait complex utilizing the vast phenotypic and genomic data collected in an applied wheat breeding programme were investigated in this study. Two breeding strategies based on various genomic-selection indices were compared, which (1) aimed to select high-protein genotypes with acceptable yield potential and (2) develop high-yielding varieties, while maintaining protein content. The prediction accuracy of preliminary yield trials could be strongly improved when combining phenotypic and genomic information in a genomics-assisted selection approach, which surpassed both genomics-based and classical phenotypic selection methods both for single trait predictions and in genomic index selection across years. The employed genomic selection indices mitigated furthermore the negative trade-off between grain yield and protein content leading to a substantial selection response for protein yield, i.e. total seed nitrogen content, which suggested that it is feasible to develop varieties that combine a superior yield potential with comparably high protein content, thus utilizing available nitrogen resources more efficiently.


A Year of Fractures: a snapshot analysis of the logistics, problems and outcomes of a hospital-based fracture liaison service.
Our fracture liaison service identifies patients with low trauma fractures, determines the need for osteoporosis therapy and instigates therapy if necessary. We describe the tracking and outcome of 768 patients attending our emergency department over 1 year and discuss the problems we encountered and potential solutions. Osteoporotic fractures result in substantial morbidity, mortality and economic cost, and patients sustaining a first fracture are known to be at higher risk of sustaining future fracture. Treatment of at-risk patients has been shown to assist in prevention of future fracture including hip fracture. We established a "First Fracture Project" to identify and treat these patients in 2003. We assessed "A Year of Fractures": the logistics, outcome and problems in tracking patients presenting to our emergency department with a low trauma fracture by our fracture liaison service, over 1 year from July 2008 to June 2009. Patients were tracked by our osteoporosis nurse and offered assessment, and treatment where necessary. In 1 year, 768 patients aged 50 or over were identified from emergency department records as attending with a low trauma fracture. About 84 % of patients eventually received assessment. Of the162 patients progressing through the entire process, 74 % had osteoporosis treatment planned and/or commenced. Our fracture liaison service was effective at identifying most low trauma fracture patients at risk of further fracture and providing access to osteoporosis assessment. There were many difficulties: we outline logistic and practical issues in delivering our service and suggest potential improvements.


Valproate-Associated Parkinsonism: A Critical Review of the Literature.
Valproate was first approved as an antiepileptic drug in 1962 and has since also become established as a mood stabiliser and as prophylaxis for migraine. In 1979, Lautin published the first description of a valproate-associated extrapyramidal syndrome. Many cases of valproate-associated parkinsonism have subsequently been published, but uncertainties remain concerning its prevalence, risk factors and prognosis. The aim of this paper is to provide a critical review of the existing literature on valproate-associated parkinsonism and to discuss possible mechanisms. Literature databases were searched systematically: we identified a total of 116 patients with valproate-associated parkinsonism published in case reports, case series and systematic analyses. Prevalence rates ranged widely, between 1.4 and 75 % of patients taking valproate. There was great heterogeneity with regard to clinical presentation, age of onset, valproate dose, concomitant conditions and imaging findings. In all patients apart from three, valproate plasma concentrations were within or even below the recommended reference range when the parkinsonism occurred. Parkinsonism was reversible in the majority of patients, although recovery was often prolonged and sometimes incomplete. A dopaminergic deficit was confirmed in three of six patients investigated with dopamine transporter imaging. Seven of 14 patients who were treated with dopaminergic medication had a good response. The quality of the evidence was assessed and probability of causation was examined using the Naranjo score, which ranged from 0 to 7 (median: 5.0). Several pathophysiological mechanisms, including altered gene expression and neurotransmitter signalling, enhanced neurodegeneration or unmasking subclinical dopaminergic degeneration, could theoretically lead to valproate-associated parkinsonism. Further studies are warranted to elucidate this entity and its underlying pathophysiology.


The strength of corticomotoneuronal drive underlies ALS split phenotypes and reflects early upper motor neuron dysfunction.
Split phenotypes, (split hand, elbow, leg, and foot), are probably unique to ALS, and are characterized by having a shared peripheral input of both affected and unaffected muscles. This implies an anatomical origin rostral to the spinal cord, primarily within the cerebral cortex. Therefore, split phenotypes are a potential marker of ALS upper motor neuron pathology. However, to date, reports documenting upper motor neuron dysfunction in split phenotypes have been limited to using transcranial magnetic stimulation and cortical threshold tracking techniques. Here, we consider several other potential methodologies that could confirm a primary upper motor neuron pathology in split phenotypes. We review the potential of: 1. measuring the compound excitatory post-synaptic potential recorded from a single activated motor unit, 2. cortical-muscular coherence, and 3. new advanced modalities of neuroimaging (high-resolution imaging protocols, ultra-high field MRI platforms [7T], and novel Non-Gaussian diffusion models). We propose that muscles involved in split phenotypes are those functionally involved in the human motor repertoire used particularly in complex activities. Their anterior horn cells receive the strongest corticomotoneuronal input. This is also true of the weakest muscles that are the earliest to be affected in ALS. Descriptions of split hand in non-ALS cases and proposals that peripheral nerve or muscle dysfunction may be causative are contentious. Only a few carefully controlled cases of each form of split phenotype, using upper motor neuron directed methodologies, are necessary to prove our postulate.


An audit of structured diabetes care in a rural general practice.
To assess the impact of structured diabetes care in a rural general practice. A cohort study of structured diabetes care (care plans, multidisciplinary involvement and regular patient recall) in a large general practice in a medium-sized Australian rural town. Medical care followed each doctor's usual practice. The first 404 consecutive patients with type 2 diabetes who consented to take part in the program were evaluated 24 months after enrolment in July 2002 to December 2003. Change in cardiovascular disease risk factors (waist circumference, body mass index, serum lipid levels, blood pressure); change in indicators of risks associated with poorly controlled diabetes (glycated haemoglobin [HbA1c] concentration, foot lesions, clinically significant hypoglycaemia); change in 5-year cardiovascular disease risk. Women had a lower 5-year risk of a cardiovascular event at enrolment than men. Structured care was associated with statistically significant reductions in mean cardiovascular disease risk factors (waist circumference, - 2.6 cm; blood pressure [systolic, - 3 mmHg; diastolic - 7 mmHg]; and serum lipid levels [total cholesterol, - 0.5 mmol/L; HDL cholesterol, 0.02 mmol/L; LDL cholesterol, - 0.4 mmol/L; triglycerides, - 0.3 mmol/L]); and improvements in indicators of diabetic control (proportion with severe hypoglycaemic events, - 2.2%; proportion with foot lesions, - 14%). The greatest improvements in risk factors occurred in patients with the highest calculated cardiovascular risk. There was a statistically significant increase in the proportion of patients with "ideal" blood pressure (systolic, < 130 mmHg; diastolic, < 80 mmHg) and LDL cholesterol level (< 2.5 mmol/L) of 6.4% and 20.5%, respectively. Implementing structured care in this rural general practice coincided with improved risk factor management, and may have contributed to the improvement. The greatest benefits were in patients with high cardiovascular risk.


Optimization of the operating parameters for radon reduction on brattice induced cavern ventilation using CFD.
Cavern is a place where workers often work in underground spaces, where radon is constantly released from surrounding rock surfaces. It is of great significance to develop effective ventilation to reduce radon in underground space for safe production and occupational health. For the purpose of controlling the radon concentration level in the cavern, the influence of upstream and downstream brattice length, upstream and downstream brattice to wall width on the volume average radon concentration and the plane average radon concentration at the height of the human respiratory zone (Z = 1.6 m) in the cavern, was studied by using the CFD (Computational fluid dynamics) method, and the operating parameters of ventilation induced by the brattice are optimized. The results show that the radon concentration in the cavern can be significantly reduced by using the brattice induced ventilation compared with no ventilation auxiliary facilities. This study provides a reference for local radon-reducing ventilation design of underground cavern.


Temperature Changes and SEM Effects of Three Different Implants-Abutment Connection during Debridement with Er:YAG Laser: An Ex Vivo Study.
The study aimed to evaluate a temperature increase in, and damage to, titanium implants during flapless laser debridement. The study analyzed 15 implants with various implant-abutment connections: a two-piece implant (n = 4) with a screw abutment (IA-Implant-Abutment) and a one-piece implant with a ball type fixture (BTF, n = 4) or fix type fixture (FTF, n = 4). The implants were placed in porcine mandibles 2 mm over a bone crest to imitate a peri-implantitis. The implants were debrided in contact mode for 60 s with a Er:YAG laser at fluence of 9.95 J/cm2 (G1 group: 50 mJ/30 Hz); 19.89 J/cm2 (G2 group: 100 mJ/30 Hz); 39.79 J/cm2 (G3 group: 200 mJ/30 Hz), or a scaler with a ceramic tip (G4 control group: 4 W/20 Hz). The temperature was measured with thermocouples at implant and abutment levels. The damage in the titanium surface (n = 3, non-irradiated implants from each type) was assessed using SEM (Scanning Electron Microscopy). The temperature increase at the implant level for the laser was higher at IA in contrast with FTF and BTF. (p < 0.05) The temperature change at the abutment level was lower for the scaler in contrast to Er:YAG laser at FTF. (p < 0.0002) Er:YAG laser didn't increase the temperature by 10 °C at 100 mJ/30 Hz and 50 mJ/30 Hz. Based on SEM analysis, cracks occurred on the surface of two-piece implants and were more pronounced. Cracks and the melting of the titanium surface of two-piece implants cleaned with Er:YAG laser at 100 or 200 mJ were observed. The specimens treated with the ultrasonic scaler with a plastic curette showed the remaining dark debris on the titanium surface. We recommend using Er:YAG laser at 50 mJ/30 Hz during flapless implants debridement.


Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ.
Polycystin-1 (PC1), encoded by the PKD1 gene that is mutated in the autosomal dominant polycystic kidney disease, regulates a number of processes including bone development. Activity of the transcription factor RunX2, which controls osteoblast differentiation, is reduced in Pkd1 mutant mice but the mechanism governing PC1 activation of RunX2 is unclear. PC1 undergoes regulated cleavage that releases its C-terminal tail (CTT), which translocates to the nucleus to modulate transcriptional pathways involved in proliferation and apoptosis. We find that the cleaved CTT of PC1 (PC1-CTT) stimulates the transcriptional coactivator TAZ (Wwtr1), an essential coactivator of RunX2. PC1-CTT physically interacts with TAZ, stimulating RunX2 transcriptional activity in pre-osteoblast cells in a TAZ-dependent manner. The PC1-CTT increases the interaction between TAZ and RunX2 and enhances the recruitment of the p300 transcriptional co-regulatory protein to the TAZ/RunX2/PC1-CTT complex. Zebrafish injected with morpholinos directed against pkd1 manifest severe bone calcification defects and a curly tail phenotype. Injection of messenger RNA (mRNA) encoding the PC1-CTT into pkd1-morphant fish restores bone mineralization and reduces the severity of the curly tail phenotype. These effects are abolished by co-injection of morpholinos directed against TAZ. Injection of mRNA encoding a dominant-active TAZ construct is sufficient to rescue both the curly tail phenotype and the skeletal defects observed in pkd1-morpholino treated fish. Thus, TAZ constitutes a key mechanistic link through which PC1 mediates its physiological functions.


A model of antiglucocorticoid action for designing a potent glucocorticoid antagonist.
We have previously shown that the biological efficacy of an antiglucocorticoid is directly related to its affinity for the glucocorticoid receptor in whole cells at 37 degrees C. We have also shown that RU 486-receptor complexes differ from other antiglucocorticoid-receptor complexes in so far as their affinity is as high at 37 degrees C in whole cells as at 0 degree C in a cell-free system, whereas a decrease by a factor of 5-10 is observed with the other antagonists. The aim of the present paper was to evaluate the contributions of temperature and cellular integrity (or the biological events linked to temperature and cellular integrity) to the affinity of a steroid for its receptor for the purpose of determining the parameters favorable to high affinity, which is the prerequisite of a potent antagonist. We provide evidence showing that: (1) an increase in temperature has an unfavorable effect on the affinity of a glucocorticoid for its receptor (4-6-fold decrease between 0 and 37 degrees C), (2) RU 486, like an agonist, forms a complex with the cytosolic glucocorticoid receptor, which satisfies the criteria for an "activated" complex under "in vitro activating treatment", (3) these biological post-binding events (either agonistic or otherwise nature), which change the nature of the complexes, contribute to compensating for the negative effect of rising temperatures on their apparent dissociation constant. We conclude that potent antiglucocorticoids must have a chemical structure allowing them to induce biological post-binding events, such as receptor activation, but in an abortive form which thus effectively "traps" the receptor in a non-functional state.


Pediatricians' perspectives on COVID-19 and HPV vaccine hesitancy.
Rises in parental vaccine hesitancy, observed during the COVID-19 pandemic, threaten public health. This is especially concerning for vaccines not typically required for school-entry, such as the vaccines for COVID-19 and human papillomavirus (HPV), both of which also have much lower rates of completion compared to other adolescent vaccines. Pediatricians are well-positioned to address vaccine hesitancy and can offer insights into parents' perspectives in this area. There is evidence that pediatricians' sharing their own vaccine stories may help to address parents' concerns; yet we have little information on pediatricians' or their children's COVID-19 vaccine uptake. To address these gaps, we conducted a cross-sectional survey about Massachusetts pediatricians' behaviors and perspectives on vaccines that face significant resistance: HPV and COVID-19 vaccines. A total of 144 people initiated the survey, and 109 participants were eligible and completed the survey. Participants reported high levels of COVID-19 vaccine uptake for themselves (97%) and their children (98%). Similarities in parents' resistance toward both vaccines were identified: fear of side effects; general vaccine resistance. Pediatricians reported a rise in vaccine hesitancy since the beginning of the COVID-19 pandemic. Future research should focus on identifying strategies to build overall vaccine confidence and streamline these efforts for pediatricians.


Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.
Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL). Data mining identified 451 differentially regulated proteins. These proteins were analyzed on the basis of temporal regulation, cellular localization, and literature-mined functional information. Of the 451 proteins, 378 were clustered into six functional groups based on major clinically-relevant effects of CS in liver. MPL-responsive proteins were highly localized in the mitochondria (20%) and cytosol (24%). Interestingly, several proteins were related to hepatic stress and signaling processes, which appear to be involved in secondary signaling cascades and in protecting the liver from CS-induced oxidative damage. Consistent with known adverse metabolic effects of CS, several rate-controlling enzymes involved in amino acid metabolism, gluconeogenesis, and fatty-acid metabolism were altered by MPL. In addition, proteins involved in the metabolism of endogenous compounds, xenobiotics, and therapeutic drugs including cytochrome P450 and Phase-II enzymes were differentially regulated. Proteins related to the inflammatory acute-phase response were up-regulated in response to MPL. Functionally-similar proteins showed large diversity in their temporal profiles, indicating complex mechanisms of regulation by CS. Clinical use of corticosteroid (CS) therapy is frequent and chronic. However, current knowledge on the proteome-level effects of CS in liver and other tissues is sparse. While transcriptomic regulation following methylprednisolone (MPL) dosing has been temporally examined in rat liver, proteomic assessments are needed to better characterize the tissue-specific functional aspects of MPL actions. This study describes a functional pharmacoproteomic analysis of dynamic changes in MPL-regulated proteins in liver and provides biological insight into how steroid-induced perturbations on a molecular level may relate to both adverse and therapeutic responses presented clinically.


YAP Facilitates NEDD4L-Mediated Ubiquitination and Degradation of ACSL4 to Alleviate Ferroptosis in Myocardial Ischemia-Reperfusion Injury.
Ferroptosis is a novel iron-dependent type of cell death that takes part in the progression of myocardial ischemia/reperfusion injury (MIRI). However, the detailed mechanism of ferroptosis underlying MIRI remains unclear. This study aimed to investigate the regulatory role of yes-associated protein (YAP) in ferroptosis during MIRI. The in vivo and in vitro MIRI models were established in the Sprague-Dawley (SD) rats and H9C2 cardiomyocytes. The infarct volume, pathologic changes, cardiac function, serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK)-MB were detected. Western blotting and immunohistochemistry were performed to measure the expression of YAP, neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) and ferroptosis-related proteins. Ferroptosis was evaluated by Fe2+, malondialdehyde (MDA), LDH, glutathione (GSH), and lipid reactive oxygen species (ROS) levels. Molecular mechanism was analyzed by co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assay. YAP and NEDD4L were remarkably low expressed in MIRI models. YAP overexpression reduced myocardial infarct volume and improved cardiac function. In addition, YAP inhibited MIRI-induced ferroptosis as confirmed by reducing levels of Fe2+, MDA, LDH, lipid ROS, and ferroptosis-related protein ACSL4, and enhancing GSH level and cell viability. Mechanistically, YAP facilitated NEDD4L transcription that consequently caused ubiquitination and degradation of ACSL4, thereby restraining ferroptosis in MIRI. YAP knockdown aggravated MIRI-induced ferroptosis, which was counteracted by NEDD4L overexpression. YAP represses MIRI-induced cardiomyocyte ferroptosis via promoting NEDD4L transcription and subsequent ubiquitination and degradation of ACSL4. YAP-mediated ferroptosis inhibition might be a novel therapeutic strategy for MIRI.


Correlation between compensated patient claims and 30-day mortality.
To test if compensation claims from patients (reported to the Norwegian System of Patient Injury Compensation) are correlated with the existing quality indicator of 30-day mortality (based on data from Norwegian Patient Registry). This correlation has not been previously evaluated. The association between patient claims and 30-day mortality at hospital trust level was assessed by the Pearson correlation coefficient. The Norwegian System of Patient Injury Compensation is a governmental agency under the Ministry of Health and Care Services and deals with patient-reported complaints about incorrect treatment in the public and private healthcare services. Patient-reported claims may be an indicator of healthcare quality, as 30-day mortality. All 19 Norwegian hospital trusts. : None. Patient claims rates, 30-day mortality and Pearson correlation coefficient. Both number of deaths within 30 days and number of claims have declined over time. High correlation (0.77, P < 0.001) was found between number of deaths within 30 days and the total number of claims. In addition, an even stronger association was found with approved claims, with a correlation coefficient of 0.83 (P < 0.001). Moreover, adjusted 30-day mortality was significantly correlated with the patient-claim rate using number of bed-days as denominator, but not when using number of discharges. The results from the present study indicate an association between compensation claims from patients and 30-day mortality, suggesting that both parameters reflect the latent quality of care for the hospital trusts, but they may capture different aspects of care.


An electrophoretic analysis of sheep plasma protein labeled with Na2 75SeO3 in vivo.
Following an intravenous injection of 75Se, sodium selenite plasma samples were analyzed by two-dimensional electrophoresis. 75Se was detected by indirect autoradiography. From 0.5 to 53 hr postinjection of 75Se, 21 75Se peptides were detected. Both the isoelectric points and molecular weights of these peptides are reported. The molecular weights of the peptides ranged from 20,000 to 70,000 daltons.


Surface-associated glycosyltransferase activities in rat Sertoli cells in vitro.
We have previously demonstrated fucosyltransferase (FT) activity on mouse germ cell surfaces at different stages of spermatogenesis. To complement these findings, here we report FT activity on the Sertoli cell (SC) surface. SC isolated and cultured from 20-day-old rat testes displayed FT activity with a Vmax of 12.5 pmoles/mg protein/min and a Km of 22 microM, while purified Sertoli cell plasma membranes (SCPM) showed FT activity with a Vmax of 10 pmoles/mg protein/min and a Km of 18.2 microM for GDP-[14C]-L-fucose. Fucosyltransferase activities were 16.7 and 2.6 pmoles/mg protein/min in SC and SCPM, respectively; approximately 16% of FT activity is, therefore, on the cell surface. To test whether the expression of FT activity in SC was regulated by hormones and growth factors, SC were cultured in serum-free medium supplemented with insulin, transferrin, sodium selenite, and epidermal growth factor (medium 4F) or in 4F plus follicle-stimulating hormone, testosterone, hydrocortisone, and vitamin E (medium 8F). We found that FT activity in SC is not modulated by these hormones or growth factors (4F or 8F). For comparison with FT, galactosyltransferase (GalTase) activities in SC and SCPM were also determined. SC displayed GalTase activity with a Vmax of 50 pmoles/mg protein/min and a Km of 38.5 microM, while SCPM showed GalTase activity with a Vmax of 25 pmoles/mg protein/min and a Km of 20.8 microM for UDP-[3H]-galactose. Galactosyl-transferase activities were 29.2 and 9.6 pmoles/mg protein/min in SC and SCPM, respectively. Therefore, approximately 33% of the total cell GalTase activity was detected on the surface membranes of rat Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic and phenotypic assessments for the safety of probiotic Bacillus clausii 088AE.
In this study, we report on whole genome sequence analysis of clinically documented, commercial probiotic Bacillus clausii 088AE and genome features contributing to probiotic properties. The whole genome sequence of B. clausii 088AE generated a single scaffold of 4,598,457 bp with 44.74 mol% G + C. This assembled genome sequence annotated by the RAST resulted in 4371 coding genes, 75 tRNAs, and 22 rRNAs. Gene ontology classification indicated 39.5% proteins with molecular function, 44.24% cellular component, and 16.25% proteins involved in biological processes. In taxonomic analysis, B. clausii 088AE shared 99% identity with B. clausii DSM 8716. The gene sequences related to safety and genome stability such as antibiotic resistance (840), virulence factors (706), biogenic amines (1), enterotoxin (0), emetic toxin (0), lanthipeptides (4), prophage (4) and clustered regularly interspaced short palindromic repeats (CRISPR) sequences (11), were identified and evaluated for safety and functions. The absence of functional prophage sequences and the presence of CRISPR indicated an advantage in genome stability. Moreover, the presence of genome features contributing to probiotic characteristics such as acid, and bile salt tolerance, adhesion to the gut mucosa, and environmental resistance ensure the strains survivability when consumed as a probiotic. In conclusion, the absence of risks associated with sequences/genes in the B. clausii 088AE genome and the presence of essential probiotic traits confirm the strain to be safe for use as a probiotic.


Administrative Data Research UK.
ADR UK is helping to transform the way researchers access the UK's wealth of administrative data, enabling government policy to be informed by the best evidence available. Emma shares her insights into the ADR UK approach to making this happen, explaining why building trust is central to the ADR UK mission.


Global identification of circular RNAs in chronic myeloid leukemia reveals hsa_circ_0080145 regulates cell proliferation by sponging miR-29b.
Circular RNAs (circRNAs) are a class of non-coding RNAs that participate in various biological processes and disease pathogenesis. However, the role of circRNAs in chronic myeloid leukemia (CML) remains largely unknown. In this study, high-throughput sequencing was performed to explore the expression profile of circRNAs in CML patients for the first time, and a large number of differentially expressed circRNAs were identified. In addition, we constructed potential circRNA-miRNA interaction networks in CML, including a detailed hsa_circ_0080145-mediated competing endogenous RNA (ceRNA) regulatory network. Furthermore, functional experiments demonstrated that hsa_circ_0080145 knockdown significantly suppressed CML cell proliferation and hsa_circ_0080145 regulated CML cell proliferation by acting as an miR-29b sponge.


Differences in specificity of "DPw2-specific" cytotoxic T cell clones revealed with HLA-mutant lines: evidence that non-DP HLA genes influence recognition by some clones.
Seven allospecific cytotoxic T lymphocyte (CTL) clones derived from DPw2-specific bulk populations were characterized by three approaches to obtain a more detailed understanding of the T cell recognition of the HLA-DPw2 molecule. All seven of the clones were DPw2 specific and indistinguishable in specificity by three approaches: (a) patterns of lysis of panels of targets from normal donors; (b) inhibition of lysis by anti-class II monoclonal antibodies (mAb); (c) lysis of mutant lymphoblastoid B cell lines (LCL) with isolated loss of DP2 alpha or DP2 beta gene expression (as a result of selection for resistance to DPw2-specific CTL). However, only four of the seven CTL clones (which we designate "orthodox") lysed all mutant DPw2+ LCL tested; the other three ("heterodox") CTL clones showed reduced or no lysis of particular LCL which expressed DPw2 but had been mutagenized and selected for loss of DR expression. Cold target blocking experiments with the mutant LCL confirmed differences in: (a) specificity among CTL clones and (b) CTL-defined phenotype among serologically indistinguishable DR-DPw2+ mutant LCL. Differences were not explained by different levels of DP expression by the mutant LCL. Given the nature of the mutagens and mutations, it is highly improbable that point mutations in DP account for differences in recognition. These data suggest that non-DP HLA genes influence recognition by some DP-specific clones, potentially due to corecognition of HLA-DR alpha or another non-DP HLA product in the context of a DPw2 alpha/beta dimer.


[Influencing Factors of Adherence to Exercise Prehabilitation in Older Patients With Colorectal Cancer: A Qualitative Study].
To investigate the influencing factors of adherence to exercise prehabilitation in older patients with colorectal cancer. Based on the capacity, opportunity, and motivation of behavior change (COM-B) model, 12 older colorectal tumors patients undergoing elective surgeries at a tertiary-care hospital in Shanghai between August 2022 and December 2022 were enrolled for the study through purposive sampling. The respondents were involved in semi-structured interviews. Directed content analysis of their data was conducted to extract themes. A total of 3 themes and 8 sub-themes were deduced from the analysis, including capacity (physical ability to tolerate exercise intensity and psychological experience of worrying about exercise risks), opportunity (adequate information support and professional guidance and simple and feasible exercise prescriptions and prehabilitation conditions), motivation (the intrinsic drive to identify with the prehabilitation values, the positive drive of inherent exercise habits, the continuous drive of exercise benefits, and the dual inspiration of team spirit and family support). These themes and subthemes were identified as influencing factors of adherence to exercise prehabilitation in older patients with colorectal cancer. Prehabilitation in older patients with colorectal cancer is influenced by multiple factors. Healthcare professionals should enhance education, develop individualized prehabilitation programs, and improve the diversified social support system to enhance patients' adherence to prehabilitation exercise and maximize the benefits of prehabilitation.


From Denis Burkitt to Dar es Salaam. What happened next in East Africa?--Tanzania's story.
East Africa was at the forefront of early achievements and discoveries in paediatric oncology thanks to Denis Burkitt's seminal work. Although these successes have been built upon and continued elsewhere, they were sadly not sustained in sub-Saharan Africa for a variety of reasons. In recent years however this situation is slowly changing in countries across the continent. Tanzania is one such African country. Until very recently, survival rates of 5-10% for all children's cancers were expected. However, change has been brought about thanks to the combined efforts and commitments of the Tanzanian Ministry of Health, non-governmental organizations--such as The International Network for Cancer Treatment and Research, and Children in Crossfire-- and the participation of the private sector. Services are rapidly developing and outcomes are continuing to improve with 1-year survival rates of approximately 60% achieved. Efforts to maintain this early progress are concentrated around providing high quality local subspecialty medical training and continued local ownership of the programme.


Conditioned soils reveal plant-selected microbial communities that impact plant drought response.
Rhizobacterial communities can contribute to plant trait expression and performance, including plant tolerance against abiotic stresses such as drought. The conditioning of microbial communities related to disease resistance over generations has been shown to develop suppressive soils which aid in plant defense responses. Here, we applied this concept for the development of drought resistant soils. We hypothesized that soils conditioned under severe drought stress and tomato cultivation over two generations, will allow for plant selection of rhizobacterial communities that provide plants with improved drought resistant traits. Surprisingly, the plants treated with a drought-conditioned microbial inoculant showed significantly decreased plant biomass in two generations of growth. Microbial community composition was significantly different between the inoculated and control soils within each generation (i.e., microbial history effect) and for the inoculated soils between generations (i.e., conditioning effect). These findings indicate a substantial effect of conditioning soils on the abiotic stress response and microbial recruitment of tomato plants undergoing drought stress.


A neurophysiological analysis of working memory in amyotrophic lateral sclerosis.
Frontal lobe functions, in particular working memory (WM) and verbal fluency, have been found to be deficient in amyotrophic lateral sclerosis (ALS). To study the neural correlates of WM-impairment, ALS patients and healthy age-matched controls were subjected to two working memory tasks following the 2-back paradigm, one requiring the storage of figural information, the other storage of spatial information. A significant proportion of ALS patients were unable to perform the WM-tasks. Those who could showed worse performance in the spatial task than the controls. Event-related brain potentials recorded during the task revealed a topographical change of the working memory effect in the ALS patients. Thus, behavioral and electrophysiological data suggest an alteration of working memory, in particular for spatial information, in ALS. Additionally, the patients also took part in two Go/Nogo tasks (spatial, figural) using the same stimulus material but defining targets prior to the experiment instead of a working memory manipulation. Here, an anteriorization of the nogo-P3 was found which has been established as an index of impaired inhibitory functions.


Urology: a trip into metaverse.
Metaverse is becoming an alternative world in which technology and virtual experiences are mixed with real life, and it holds the promise of changing our way of living. Healthcare is already changing thanks to Metaverse and its numerous applications. In particular, Urology and urologic patients can benefit in many ways from Metaverse. A non-systematic literature review identified recently published studies dealing with Metaverse. The database used for this review was PubMed, and the identified studies served as the base for a narrative analysis of the literature that explored the use of Metaverse in Urology. Virtual consultations can enhance access to care and reduce distance and costs, and pain management and rehabilitation can find an incredible support in virtual reality, reducing anxiety and stress and improving adherence to therapy. Metaverse has the biggest potential in urologic surgery, where it can revolutionize both surgery planning, with 3D modeling and virtual surgeries, and intraoperatively, with augmented reality and artificial intelligence. Med Schools can implement Metaverse in anatomy and surgery lectures, providing an immersive environment for learning, and residents can use this platform for learning in a safe space at their own pace. However, there are also potential challenges and ethical concerns associated with the use of the metaverse in healthcare. This paper provides an overview of the concept of the metaverse, its potential applications, challenges, and opportunities, and discusses the implications of its development in Urology.


Methylphenidate effects in attention deficit/hyperactivity disorder: electrodermal and ERP measures during a continuous performance task.
Previous research investigating the effects of stimulants, such as methylphenidate (MPH), on children with attention deficit/hyperactivity disorder (AD/HD) has rarely included autonomic measures of arousal. Our aim was to clarify the effects of MPH on central and autonomic measures in AD/HD children during a continuous performance task (CPT) using a naturalistic open-label study. Thirty-six boys (18 AD/HD and 18 control) participated in a CPT over two trial periods, allowing a more valid estimate of the effects of medication, rather than assuming that retesting per se has no substantial impact. MPH was administered to the AD/HD group 1 h prior to the second trial. Errors and reaction time (RT) were recorded as measures of performance, electrodermal activity as an autonomic nervous system measure and event-related potentials (ERPs) as an index of central nervous system activity. AD/HD children made more errors than controls in the first session, but no group differences were found after medication. No significant differences were observed for RT. Skin conductance level was found to be lower in AD/HD children than controls, but this difference was also ameliorated after medication. Conversely, mean skin conductance response to target stimuli was found not to differ between groups during the initial test phase but became significantly different in phase 2. ERP data showed topographic differences between groups in N1, P2, N2 and P3 at the initial test phase, which were reduced at the second test. Stimulant medication ameliorated some of the dysfunctions in AD/HD children, which are reflected in behavioural and ERP measures. These results, in combination with general differences in electrodermal activity, support a hypo-arousal model of AD/HD, which can explain the action of MPH in these children.


Systemizing influences attentional processes during the Navon task: an fMRI study.
Systemizing ability exists on a spectrum, with a high systemizing style meaning proficiency in analysing the rules of a system, to predict how that system works. This study uses fMRI to investigate a spectrum of low to high systemizing, to assess whether individuals with a high systemizing style exhibit an attentional bias towards local details. This is the first study to test for the neural correlates of systemizing. Participants with a range of scores on the Systemizing Quotient (SQ) were given a version of the Navon task during fMRI, which elicits perceptual conflict between local and global levels of visual attention. SQ score was correlated with a focus on local detail in the behavioural study. During conditions eliciting perceptual conflict SQ score was associated with increased activation in the lateral prefrontal, parietal and extrastriate visual cortices. However, neural investigations did not imply a neural correlate of systemizing during local processing per se. Results are discussed in terms of a heightened ability to maintain an attentional set in those with a high systemizing cognitive style.


Rehabilitative training paired with peripheral stimulation promotes motor recovery after ischemic cerebral stroke.
Spontaneous recovery of ischemic stroke is very limited and often results in the loss of motor and sensory function. Till now, rehabilitative training is the most widely accepted therapy to improve long-term outcome. However, its effectiveness is often suboptimal, largely due to a sharp decline of neuroplasticity in adults. In this study, we hypothesized that a combination of proprioceptive stimulation and rehabilitative training will promote neuroplasticity and functional recovery post injury. To test this hypothesis, we first established a photothrombotic stroke model that lesions the hindlimb sensorimotor cortex. Next, we demonstrated that injecting Cre-dependent AAV-retro viruses into the dorsal column of PV-Cre mice achieves specific and efficient targeting of proprioceptors. With chemogenetics, this method enables chronic activation of proprioceptors. We then assessed effects of combinatorial treatment on motor and sensory functional recovery. Our results showed that pairing proprioceptive stimulation with rehabilitative training significantly promoted skilled motor, but not tactile sensory functional recovery. This further led to significant improvement when compared to rehabilitation training or proprioceptor stimulation alone. Mechanistically, combinatorial treatment promoted cortical layer V neuronal mTOR activity and sprouting of corticospinal axon into the area where proprioceptive afferents terminate in the denervated side of the spinal cord. Serving as a proof of principle, our study thus provided novel insights into the application of combining proprioceptive stimulation and rehabilitative training to improve functional recovery of ischemic stroke and other traumatic brain or spinal cord injuries.


An endogenous serotonergic rhythm acting on 5-HT(2A) receptors may be involved in the diurnal changes in tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in female rats.
The central serotonergic system has long been known to have a stimulatory role on the secretion of prolactin (PRL). The integrity of serotonergic neurotransmission is essential for the expression of the estrogen-induced afternoon PRL surge. Whether its effect on PRL involves change in the activity of tuberoinfundibular dopaminergic (TIDA) neurons has not been ascertained. In adult ovariectomized rats treated with estrogen, depletion of central serotonin (5-HT) by 5,7-dihydroxytryptamine (5,7-DHT, 200 microg/rat, i.c.v.) effectively prevented the afternoon fall in TIDA neuronal activity (using the levels of 3,4-dihydroxyphenylalanine and 3, 4-dihydroxyphenylacetic acid (DOPAC), and the ratio of DOPAC/dopamine in the median eminence as indices), and blunted the afternoon PRL surge. A single injection of a 5-HT(2A) receptor antagonist, ketanserin (5 mg/kg, i.p. at 12.00 h), also had the same effects on the diurnal changes in TIDA neuronal activity and PRL secretion as the treatment with 5,7-DHT did. Intracerebroventricular injection of a 5-HT(2) receptor agonist 2, 5-dimethoxy-4-iodoamphetamine (DOI) in the morning inhibited the TIDA neuronal activity and stimulated PRL secretion in a dose-dependent manner; while injection of a 5-HT(1) agonist, 8-hydroxy-dipropylaminotetralin, was without effect. Injection of DOI in 5,7-DHT-pretreated rats at 14.30 h also lowered the TIDA neuronal activity and reinstated the PRL surge. In all, endogenous 5-HT, acting through the 5-HT(2A) receptor, appears to exhibit an inhibitory effect on TIDA neuronal activity during the afternoon, which is essential for the PRL surge.


Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization.
Focal brain injury in mice induced c-fos mRNA and protein in neurons throughout the damaged neocortex, including the piriform and the entorhinal cortices, as well as in nonneural brain cells (e.g., glia, pia, ependyma). The pattern of c-fos induction after injury suggested that injury led to spreading depression which then led to c-fos induction in neurons. Human neurons in the temporal cortex and hippocampus also showed c-fos protein induction after neurosurgical trauma. The c-fos mRNA and protein induction in mouse neurons was prevented by the noncompetitive NMDA antagonist ketamine but only partially inhibited by the voltage-dependent calcium channel antagonist nifedipine and the calmodulin antagonist trifluoperazine. The c-fos protein induction in nonneural brain cells after injury was not affected by these drugs. Thus, induction of c-fos in neocortical neurons after focal brain injury is partly NMDA receptor mediated.


Should hemodialysis patients with atrial fibrillation undergo systemic anticoagulation? A cost-utility analysis.
Approximately 14% of hemodialysis patients have atrial fibrillation. Hemodialysis patients with atrial fibrillation appear to be at increased risk of both thromboembolic complications and bleeding. Furthermore, there is uncertainty regarding the efficacy of warfarin or acetylsalicylic acid (ASA) therapy for preventing strokes in this subgroup because they were excluded from relevant trials. We performed a cost-utility analysis. Probabilistic sensitivity analysis was used to incorporate parameter uncertainty into the model. Expected value of perfect information and scenario analyses were performed to identify the important drivers of the decision and focus future research. Base case was a 60-year-old male hemodialysis patient in the United States. A Markov Monte Carlo microsimulation model was constructed from the perspective of the health care payer, and patients were followed up during their lifetime. We compared 3 alternative treatment strategies for permanent atrial fibrillation in hemodialysis patients: warfarin, ASA, or no treatment. Quality-adjusted survival and cost. ASA and warfarin both prolonged survival compared with no treatment (0.06 and 0.15 quality-adjusted life-years [QALYs], respectively). ASA was associated with an incremental cost-effectiveness ratio of $82,100/QALY. Warfarin provided additional benefits at a cost of $88,400 for each QALY gained relative to ASA. At a threshold of $100,000/QALY, the probabilities that no treatment, warfarin, and ASA were the most efficient therapy were 20%, 58%, and 23%, respectively. Parameterization data and costs were taken from US studies and may not be generalizable to other countries. Peritoneal dialysis patients were not included in the analysis. The high future cost of hemodialysis constrains incremental cost-effectiveness ratios to values greater than commonly cited thresholds ($50,000/QALY). Based on available evidence, warfarin appears to be the optimal therapy to prevent thromboembolic stroke in hemodialysis patients with atrial fibrillation. Additional study is required to determine the efficacy of warfarin and risk of bleeding complications in this population so that patients can make a more informed choice.


Isolation of Legionella pneumophila from hotels of Greece.
Twenty water samples collected from 6 hotels situated in various areas of Greece were examined for the presence of Legionella pneumophila and Legionella-like organisms. Five of the six hotels included in this investigation were associated with cases of legionellosis. Legionella pneumophila serogroups 1 and 8 were isolated from four of six hotels, mainly from the hot water supply system. This is the first isolation and identification of L. pneumophila in Greece.


Exploring 129Xe NMR parameters for structural investigation of biomolecules: relativistic, solvent, and thermal effects.
In recent years, the study of new probes has aroused great interest in the scientific community around the world. Therefore, in the present work, we present a potential candidate for a new spectroscopic probe, the Xe(CO)3(NNO) conjugated to 2-(4'-aminophenyl) benzothiazole complex, XeABT. For this proposal, chemical shift calculations at the DFT level were performed; thus, a factorial design was carried out in order to choose the best computational method. The best combination was the base function ZORA-def2-TZVP, with the functional PBE0 and considering the relativistic effects with the ZORA implementation. Our findings reveal that the 129Xe chemical shifts are affected by thermal and solvent effects, and considering an enzymatic environment, a significant decrease in δ(129Xe) values is observed, suggesting with the XeABT complex it may be a promising spectroscopic probe.


The susceptible period for deprivation-induced myopia in tree shrew.
To examine the susceptible period for deprivation-induced myopia, six groups of tree shrew pups (Tupaia glis belangeri) were monocularly deprived for 12 days with an opaque occluder starting 7, 15, 21, 33, 48, or 63 days after natural eyelid opening. Compared to the untreated fellow control eye, significant myopia and vitreous chamber elongation were produced by the deprivation in all six groups. The effect was greater in the middle three groups in comparison with the youngest and the two oldest groups and the amount of induced myopia and axial elongation was not proportional to the normal rate of axial growth. The peak period of susceptibility was between approximately 15 and 45 days after eye opening during the juvenile, slow-elongation phase of ocular development when the eye is within 7% of its adult axial length. Significant myopia and axial elongation were also induced in adult animals by 70 days of monocular deprivation. To examine recovery from deprivation-induced myopia, the occluder was removed at the end of the 12 day deprivation period. After an additional 48 days of binocular visual experience, no significant myopia was present in the previously deprived eyes in any experimental group. During the recovery period, the elongation rate of the previously deprived eyes was reduced in comparison with the control eyes while normal corneal flattening and lens development continued, thus reducing the myopia. No difference in corneal curvature, relative to the untreated control eyes, was found after deprivation or after the recovery period. Data are presented which suggests that changes in the thickness of the choroid may occur in this mammal during deprivation and recovery that are in the same direction, but of smaller magnitude, than those reported in the chicken. The results of this study provide evidence that visually guided emmetropization occurs in this mammalian species during a period of ocular development analogous to the juvenile period in humans.


The effect of terminal impedance on aortic morphology and hemodynamics: an in vitro phantom study using flow field visualization.
To investigate the risk factors for aortic dissection tearing, we fabricated a simplified patient-specific aortic silicone phantom using the brush-spin-coating method. The aortic phantom only includes the aorta from the ascending aorta to the descending aorta, without other branches. We designed two experiments to investigate the alteration of aortic morphology and intravascular hemodynamics using the particle image velocimetry method. The results revealed dilation and elongation of the aortic phantom, especially the ascending aorta, after the phantom's terminal resistance was increased. Additionally, the particle image velocimetry results demonstrated an increased vortex region, which caused the inner side of the aortic wall to become scoured by blood. This study suggests that the deformation of the inner side aortic wall and the change in hemodynamics in response to the increased terminal resistance may be a risk factor for aortic tearing and should be monitored.


Association of diabetes with anxiety: a systematic review and meta-analysis.
Anxiety has been shown to be associated with poor outcomes in people with diabetes. However, there has been little research which has specifically examined whether diabetes mellitus is associated with an increased likelihood of co-morbid anxiety. The aim of this systematic review and meta-analysis was to determine whether people with diabetes are more likely to have anxiety disorders or elevated anxiety symptoms than people who do not have diabetes. A systematic review was performed by three independent reviewers who searched for articles that examined the association between anxiety and diabetes in adults 16 or older. Those studies that met eligibility criteria were put forward for meta-analysis using a random-effects model. A total of twelve studies with data for 12,626 people with diabetes were eligible for inclusion in the systematic review and meta-analysis. Significant and positive associations were found for diabetes with both anxiety disorders, 1.20 (1.10-1.31), and elevated anxiety symptoms, 1.48 (1.02-1.93). The pooled OR for all studies that assessed anxiety was 1.25 (1.10-1.39). Results from this meta-analysis provide support that diabetes is associated with an increased likelihood of having anxiety disorders and elevated anxiety symptoms.


Robotic eTEP versus IPOM evaluation: the REVEAL multicenter randomized clinical trial.
For small to medium-sized ventral hernias, robotic intraperitoneal onlay mesh (rIPOM) and enhanced-view totally extraperitoneal (eTEP) repair have emerged as acceptable approaches that each takes advantage of robotic instrumentation. We hypothesized that avoiding mesh fixation in a robotic eTEP repair offers an advantage in early postoperative pain compared to rIPOM. This is a multi-center, randomized clinical trial for patients with midline ventral hernias ≤ 7 cm, who were randomized to rIPOM or robotic eTEP. The primary outcome was pain (0-10) on the first postoperative day. Secondary outcomes included same-day discharge, length of stay, opioid consumption, quality of life, surgeon workload, and cost. Between November 2019 and November 2021, 100 patients were randomized (49 rIPOM, 51 eTEP) among 5 surgeons. Pain on the first postoperative day [median (IQR): 5 (4-6) vs. 5 (3.5-7), p = 0.66] was similar for rIPOM and eTEP, respectively, a difference maintained following adjustments for surgeon, operative time, baseline pain, and patient co-morbidities (difference 0.28, 95% CI - 0.63 to 1.19, p = 0.56). No differences in pain on the day of surgery, 7, and 30 days after surgery were identified. Same-day discharge, length of stay, opioid consumption, and 30-day quality of life were also comparable, though rIPOM required less surgeon workload (p < 0.001), shorter operative time [107 (86-139) vs. 165 (129-212) min, p < 0.001], and resulted in fewer surgical site occurrences (0 vs. 8, p = 0.004). The total direct costs for rIPOM and eTEP were comparable [$8282 (6979-11835) vs. $8680 (7550-10282), p = 0.52] as the cost savings for eTEP attributable to mesh use [$442 (434-485) vs. $69 (62-76), p = < 0.0001] were offset by increased expenses for operative time [$669 (579-861) vs. $1075 (787-1367), p < 0.0001] and use of more robotic equipment [$760 (615-933) vs. $946 (798-1203), p = 0.001]. The avoidance of fixation in a robotic eTEP repair did not reveal a benefit in postoperative pain to offset the shorter operative time and surgeon workload offered by rIPOM.


Clinical applications of quantitative T2 determination: a complementary MRI tool for routine diagnosis of suspected myelination disorders.
Though magnetic resonance imaging (MRI) plays an important role in studying pathological changes in central nervous system, a quantitative measure of contrast variance on MRI, allowing the detection of subtle signal variances in pathological processes, is not readily available for routine imaging. We report on the first experiences with evaluation of routine T2 relaxation time measurement as a diagnostic tool in routine imaging of suspected myelination disorders. Twenty patients suffering from defined or suspected myelination disorders were examined by MRI. T2 relaxation time maps of the brain were derived from a triple spin echo sequence. T2 values were measured for each patient by regions of interest (ROI) analysis. As references age-dependent T2 prediction values in normal maturating brains were calculated by using a biexponentional function reported earlier. Deviations from these prediction values were used as an assisting tool both for detection of pathology and for monitoring of changes over time. These quantitative results were compared to conventional visual inspections by two independent neuroradiologists. In 18 patients with single diagnostic MRI, the T2 measurements were more graduated or definite in 9/18 cases, confirmatory in 9/18 cases. In two patients with MRI follow up, the dynamic clinical course of the disease had no correlate in visual inspection of the images but was associated with the quantitative T2 values. Quantitative T2 measurement is a promising tool for routine imaging as a complementary method in detecting and monitoring of suspected myelination disorders.