Differentially expressed microRNA profiles in exosomes from vascular smooth muscle cells associated with coronary artery calcification.
The pathogenesis of coronary artery calcification (CAC) in coronary heart disease (CHD) is mediated by exosomes derived from vascular smooth muscle cells (VSMCs). However, little is known about their underlying mechanism. In this study, we aimed to investigate the differentially expressed miRNAs in VSMCs undergoing induced calcification. A cellular calcification model was established using the mouse VSMC line MOVAS-1. Calcium deposition was evaluated by Alizarin Red staining. Exosome sizes were determined by Nanoparticle Tracking Analysis (NTA), and exosome morphology was examined by transmission electron microscopy (TEM). The expression of exosome and calcification biomarkers was analyzed by quantitative real-time PCR (qPCR) and western blotting. Differential miRNA profiles were determined by deep sequencing and bioinformatics. Protein levels in VSMCs experiencing interference by a miR-324-3p inhibitor were detected by western blotting. The MOVAS-1 calcification model was confirmed by Alizarin Red staining and expressional alteration of α-SMA, BMP-2, OPN, and MGP. Exosomes from the calcification model showed expression of exosomal biomarkers and regular exosome diameters, which caused significant calcification in MOVAS-1 cells. In total, 987 and 92 miRNAs were significantly upregulated and downregulated in exosomes from the cellular calcification model as compared with those from MOVAS-1 cells, respectively. Target genes of differential miRNAs were involved in various biological processes such as development, metabolism, and cellular component organization and biogenesis as well as multiple signaling pathways such as protein kinase B (AKT) signaling. The most differentially expressed miRNAs were validated by qPCR, which showed that mmu-let-7e-5p was downregulated and mmu-miR-324-3p was upregulated in exosomes from the MOVAS-1 cellular calcification model. The expression of IGF1R was increased, and the expressions of PIK3CA and MAP2K1 were reduced in MOVAS-1 transfected with a miR-324-3p inhibitor. microRNA profiles were significantly altered in exosomes from VSMCs undergoing calcification.


Development of a risk index for prediction of abnormal pap test results in Serbia.
Serbia is one of the countries with highest incidence and mortality rates for cervical cancer in Central and South Eastern Europe. Introducing a risk index could provide a powerful means for targeting groups at high likelihood of having an abnormal cervical smear and increase efficiency of screening. The aim of the present study was to create and assess validity ofa index for prediction of an abnormal Pap test result. The study population was drawn from patients attending Departments for Women's Health in two primary health care centers in Serbia. Out of 525 respondents 350 were randomly selected and data obtained from them were used as the index creation dataset. Data obtained from the remaining 175 were used as an index validation data set. Age at first intercourse under 18, more than 4 sexual partners, history of STD and multiparity were attributed statistical weights 16, 15, 14 and 13, respectively. The distribution of index scores in index-creation data set showed that most respondents had a score 0 (54.9%). In the index-creation dataset mean index score was 10.3 (SD-13.8), and in the validation dataset the mean was 9.1 (SD=13.2). The advantage of such scoring system is that it is simple, consisting of only four elements, so it could be applied to identify women with high risk for cervical cancer that would be referred for further examination.


Isolated osteochondral fracture of the metatarsal head of lesser toes.
Isolated fracture of the metatarsal head is very rare and no consensus has been reached regarding their best management. We reported four cases of isolated osteochondral fracture of the metatarsal head with different method of treatment to achieve the common goal of restoration of the congruity of the metatarsal head.


Steady-state kinetics and spectral properties of Corynebacterium sarcosine oxidase.
The overall reaction kinetics of Corynebacterium sarcosine oxidase were investigated and the reaction was shown to follow a ping-pong, bi-bi mechanism with two substrates, sarcosine and molecular oxygen. Sarcosine analogs, such as acetate, propionate and methoxyacetate, were competitive inhibitors of the reaction. Acetate caused characteristic alterations in optical and circular dichroic spectra, indicating that the microenvironment of the substrate-binding region of the enzyme increased in hydrophobicity on binding with the substrate analog. The dissociation constants of the analogs calculated from the spectral changes were in agreement with the kinetic inhibition constants. Inorganic metallic ions were also inhibitory. Of interest was the finding that the inhibition by Hg2+ was proportional to the square of its concentration, which suggests that at least two sulfhydryl groups are related to the catalytic activity of the enzyme.


Prolactin-producing pituitary adenoma in a 9 year old boy.
A boy aged 9 years and 8 months was evaluated for headache and an enlarged sella. His neurological status and visual fields were normal. After injection of radiographic contrast agent, computerized axial tomography showed evidence of an intrasellar tumor. The most striking endocrine abnormalities were growth hormone insufficiency after arginine infusion and after insulin-induced hypoglycemia, and excessively elevated prolactin levels ranging between 1220 ng/ml and 1560 ng/ml. A slightly granulated, acidophilic pituitary adenoma was selectively removed by the trans-sphenoidal approach. The function of the anterior pituitary improved post-operatively. Growth hormone secretion after insulin-induced hypoglycemia returned to normal, and the basal serum prolactin levels decreased, but are still three times higher than normal.


Rare duplication or deletion of exons 6, 7 and 8 in CYBB leading to X-linked chronic granulomatous disease in two patients from different families.
Chronic granulomatous disease (CGD) is a rare congenital disorder in which phagocytes cannot generate superoxide (O(2)(-)) and other microbicidal oxidants due to mutations in one of the five components of the O(2)(-)-generating NADPH oxidase complex. The most common form is caused by mutations in CYBB on the X chromosome, encoding gp91phox, the enzymatic subunit of the phagocyte NADPH oxidase. Here, we report two rare cases of male X-linked CGD patients, one caused by a 5.7-kb duplication of a region containing CYBB exons 6 to 8 and the other caused by a deletion of this same region. We found both the duplication in patient 1 and the deletion in patient 2 to be bordered by a GT repeat. Indeed, in control DNA, the 3' part of CYBB intron 5 contains a GT repeat and the 5' part of intron 8 also contains such a repeat. Duplication of exons 6, 7 and 8 in patient 1 was probably caused by a non-homologous crossing over between the two GT repeats. The deletion found in patient 2 probably arose from a similar misalignment. The results found in these patients were confirmed by multiplex ligation-dependent probe amplification. The clinical profile of XCGD is severe in both patients.


Cholesterol and oxygenated cholesterol concentrations are markedly elevated in peripheral tissue but not in brain from mice with the Niemann-Pick type C phenotype.
Niemann-Pick disease type C (NP-C) is a rare genetic disorder characterized by progressive neurodegeneration, frequent developmental delay and early death. Tissues of affected individuals accumulate large quantities of free cholesterol in lysosomes. Because cytotoxic oxygenated derivatives of cholesterol are known to form readily when cholesterol concentrations are elevated, we searched for these compounds in liver, kidney, spleen and brain from mice with the NP-C phenotype. In order of abundance, we identified 7 alpha- and 7 beta-hydroxycholesterol, 5 alpha, 6 alpha-epoxycholestan-3 beta-ol, 4 beta-hydroxycholesterol, cholest-4-en-3 beta, 7 alpha-diol and cholest-4-en-3 beta, 6 beta-diol in most tissue samples. Cholesterol concentrations in affected mice were increased 3-fold in kidney and 7- to 8-fold in spleen and liver compared to controls (all p < 0.001) but were unchanged in brain. Although oxysterol levels were markedly elevated in nonbrain tissue, the oxysterol and cholesterol concentrations increased proportionally so that oxysterols expressed as percentage of total sterols were the same for all animals (0.34 +/- 0.19% averaged over all organs in affected animals vs 0.40 +/- 0.42% in control mice). In contrast to peripheral tissue, we could not detect any increase in either absolute or relative oxysterol levels in the brains of affected and control mice (49 +/- 61 vs 53 +/- 43 micrograms/g wet weight and 0.45 +/- 0.52 vs 0.47 +/- 0.37%, respectively). Thus, brain sterols are normal in NP-C mice and it is unlikely that an accumulation of cytotoxic oxygenated derivatives of cholesterol could account for the progressive neuropathology seen in the disease.


Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor beta-chain gene.
The development of T cells within the thymus is not well understood. It is known that thymocytes are derived from a progenitor cell in the bone marrow, the prothymocyte, and that cells in the subcapsular area of the thymus can give rise to progeny in both the cortex and the medulla. However, it is not clear whether all medullary thymocytes are necessarily derived from cortical cells. In particular, it has been difficult to distinguish intrathymic progenitor cells. Recently, however, Lesley et al. have defined a thymocyte subpopulation which can be isolated by treatment of the thymus with cytotoxic anti-Thy-1 antibodies and that seems to be enriched for thymocyte progenitors as measured first by its ability to repopulate transiently the thymus of an irradiated host, and second, by its high content of cells bearing Pgp-1 (refs 10, 11), a cell-surface glycoprotein of relative molecular mass 95,000 that is present on most or all prothymocytes of the bone marrow and on fetal thymocytes, but on only a few per cent of cells in the adult thymus. We show here that the gene encoding the beta-chain of the T-cell receptor for antigen, which is rearranged during T-cell ontogeny, is predominantly in the germline configuration in these cells.


Predictive Value of Acute Phase Proteins for the Short-Term Outcome of Meningoencephalitis of Unknown Origin in Dogs.
Meningoencephalitis of unknown origin (MUO) is one of the most common inflammatory diseases of the central nervous system (CNS). The study evaluates the possible increase and the potential role of acute phase proteins (APPs) and other inflammatory serum parameters as biomarkers predicting the short-term outcome of dogs with meningoencephalitis of unknown origin (MUO). A retrospective cohort study was designed. The APP profile and other markers of systemic inflammation of forty-eight client-owned dogs with a new diagnosis of MUO were compared between 7-day survival and non-survival dogs diagnosed with MUO. Thirty-nine (81%) dogs were alive at the end of the 7-day follow-up period, while 9 (19%) dogs died or were euthanized because of MUO. None of the 11 markers of inflammation studied were different between the survived and non-survived dogs; for this reason, none of them could be used as a predictor of the short-term outcome based on the results of the present study. This confirms that even though MUO is often associated with a severe inflammatory status of the central nervous system (CNS), this condition is probably isolated exclusively to the CNS.


Long noncoding RNA BBOX1-AS1 increased radiotherapy sensitivity in colorectal cancer by stabilizing and activating PFK1.
Our study explored the effect of long noncoding RNA BBOX1-AS1 on colorectal cancer (CRC) radiosensitivity in vivo and in vitro. Differentially expressed lncRNAs in CRC were screened using a bioinformatics database and an online prediction website. The expression of BBOX1-AS1 in tissue samples was analyzed via real-time quantitative PCR (RT-qPCR). Subcellular localization of BBOX1-AS1 in CRC cells was analyzed using fluorescence in situ hybridization (FISH). The correlation between BBOX1-AS1 and PFK1 expression levels in CRC tissues was analyzed via Pearson's correlation coefficient. The effect of BBOX1-AS1 on PFK1 stability was investigated using RNA and protein stability testing. RNA Binding Protein Immunoprecipitation (RIP) and RNA pull-down assays were used to confirm the binding of BBOX1-AS1 to PFK1. BBOX1-AS1 was highly expressed in CRC and associated with poor prognosis. Similarly, it was highly expressed in CRC tissues and CRC cell lines. In addition, BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells and inhibited apoptosis. RIP and RNA pull-down experiments confirmed that BBOX1-AS1 bound to PFK1. RNA stability and protein stability experiments showed that BBOX1-AS1 affected the stability of PFK1 mRNA and protein. Furthermore, we confirmed that BBOX1-AS1 increased radiation resistance through the regulation of PFK1 expression. BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells through stabilization of the expression of PFK1. BBOX1-AS1 also inhibited CRC cell apoptosis and increased radiotherapy resistance in CRC cells.


Temporary inactivation of the rostral perirhinal cortex induces an anxiolytic-like effect on the elevated plus-maze and on the yohimbine-enhanced startle response.
The present study investigated whether the rostral perirhinal cortex is involved in aversive information processing, particularly in unconditioned fear (anxiety). We temporarily inactivated the rostral perirhinal cortex by local injections of the GABA(A) agonist muscimol (0.0, 1.1, and 4.4 nmol/0.5 microl) and tested whether these injections affected the behavior of rats in the elevated plus-maze and in the yohimbine-enhanced startle test. Temporary inactivation of the rostral perirhinal cortex increased the number of open arm entries and the open arm ratio in the elevated plus-maze. In addition, startle response enhancement caused by the anxiogenic drug yohimbine was reduced by perirhinal cortex inactivation. Taken together, these data clearly show that the rostral perirhinal cortex is involved in the processing of emotional stimuli and is critical for the expression of unconditioned fear (anxiety).


Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats.
It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper-responsiveness of wide dynamic range neurons (WDR) and Toll-like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI, in parallel with thermal hyperalgesia, the expression of TLR4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post-injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyper-responsiveness of WDR neurons in CCI rats. The results of this study indicate that post-injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper-responsiveness. This study confirms that post-injury modulation of microglial activity is a new strategy for treating neuropathic pain.


Effect of a novel prosthetic anal neosphincter on human colonic blood flow.
An artificial anal sphincter has been developed which aimed to simulate the normal physiology of the anorectum. As a prelude to human implantation the present study reports the effect of inflation of this device on colonic perfusion in patients undergoing colectomy, which was assessed by using a laser Doppler scanner. Eleven patients (median age 49.8 (range 24.3-78.7) years) were studied. Five patients had inflammatory bowel disease (IBD). The neosphincter was placed around the bowel and progressively inflated. The model was designed so that blood flow changes to the colon under the neosphincter would be reflected in the distal segment of the bowel, which could be scanned by the laser Doppler scanner. The blood flow in the colon distal to the device was significantly higher in patients with IBD (mean(s.e.m.) 288.6(71.9) versus 211.1(57.6) perfusion units; P < 0.001). The mean(s.e.m.) 'biological zero' value was 46(14) perfusion units. Blood flow distal to the neosphincter decreased progressively with increased sphincteric compression by 0.66 per cent per mmHg applied pressure in controls and 0.35 per cent per mmHg in patients with IBD (P < 0.05). These results suggest that at the planned operating occlusion pressure (less than 45 mmHg) this neosphincter should not put the vascularity of the human colon at risk.


Chemical biology on the brain.
A two-day symposium on chemical neurobiology revealed an open frontier for researchers at the interface of chemistry and neuroscience.


LCA of municipal wastewater treatment.
Wastewater treatment plants play a significant role in minimizing environmental pollution by treating wastewater and reducing the release of contaminants into the environment. However, their operation can still have an environmental footprint. Therefore, Life Cycle Assessment (LCA) of wastewater treatment provides a comprehensive framework to quantify the environmental impact of plants across various categories. By conducting LCA assessments, the environmental impacts of different scenarios or treatment technologies can be compared, enabling decision-makers to identify the most environmentally friendly options. This information helps in optimizing the plant's design, operation, and resource allocation to minimize their environmental burden. The current research hypothesis was to conduct an LCA of a typical activated sludge plant in Greece, considering three different scenarios in order to provide an innovative take on wastewater treatment plant foam waste and utilize them for the production of biogas through anaerobic digestion. The assessment was carried out using OpenLCA software as well as EcoInvent v3.3. database. The study focused on the impact assessment of five categories (eutrophication potential, acidification potential, global warming potential, ozone depletion, and photochemical ozone creation). The results indicated that the baseline scenario had the highest impact on these categories, followed by Scenario I, while Scenario II had the least impact. Additionally, the cumulative energy demand assessment showed that the baseline scenario required significantly more energy compared to Scenarios I and II. However, Scenario II, which involved fine screens and utilization of biogas, exhibited the highest energy production, thereby reducing the overall energy demands for the system. Based on these findings, it is crucial for wastewater treatment facilities to actively pursue energy demand mitigation strategies by implementing energy-efficient technologies and utilizing biogas. These measures not only contribute to environmental protection but also promote a greener and more sustainable future for WWTP operations.


2-Aminopurine inhibits lipid accumulation induced by apolipoprotein E-deficient lipoprotein in macrophages: potential role of eukaryotic initiation factor-2alpha phosphorylation in foam cell formation.
We previously reported that apolipoprotein (Apo) E-deficient, ApoB48-containing (E(-)/B48) lipoproteins inhibited expression of lysosomal hydrolase and transformed mouse peritoneal macrophages (MPMs) into foam cells. The present study examined the effect of 2-aminopurine (2-AP), an inhibitor of eukaryotic initiation factor (eIF)-2alpha phosphorylation, on E(-)/B48 lipoprotein-induced changes in gene expression and foam cell formation. Our data demonstrated that E(-)/B48 lipoproteins enhanced phosphorylation of eIF-2alpha in macrophages. Incubation of MPMs with E(-)/B48 lipoproteins inhibited the translation efficiency of mRNAs encoding lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor, with a parallel reduction in the level of these proteins. Addition of 2-AP to the culture media alleviated the suppressive effect of E(-)/B48 lipoproteins on lysosomal hydrolase mRNA translation, increased macrophage degradation of E(-)/B48 lipoproteins, and inhibited foam cell formation. Transfection of MPMs with a nonphosphorylatable eIF-2alpha mutant also attenuated the suppressive effect of E(-)/B48 lipoproteins on expression of lysosomal acid lipase, associated with a reduced accumulation of cellular cholesterol esters. This is the first demonstration that ApoE-deficient lipoproteins inhibit lysosomal hydrolase synthesis and transform macrophages into foam cells through induction of eIF-2alpha phosphorylation.


Translating drug resistant tuberculosis treatment guidelines to reality in war-torn Kandahar, Afghanistan: A retrospective cohort study.
Afghanistan is affected by one of the world's longest protracted armed conflicts, frequent natural disasters, disease outbreaks and large population movements and it suffers from a high burden of tuberculosis (TB), including rifampicin-resistant TB (RR-TB). The study shows Médecins Sans Frontières' experiences with care for patients with RR-TB in Kandahar Province. We describe the uptake of RR-TB treatment, how World Health Organisation criteria for the choice between the short and an individualized regimen were implemented, and treatment outcomes. This is a retrospective cohort analysis of routinely collected data from RR-TB patients enrolled in care from 2016 until 2019. Descriptive analysis was performed to present characteristics of patients and treatment outcomes. Multivariable Cox analysis was performed to identify risk factors for having an unfavourable treatment outcome. Out of 146 enrolled RR-TB patients, 112 (76.7%) started treatment: 41 (36.6%) and 71 (63.4%) with the short and individualized treatment regimen, respectively. Of 82 with results for fluoroquinolone susceptibility, 39 (47.6%) had fluoroquinolone-resistant TB. Seven patients with initially fluoroquinolone-resistant TB and three pregnant women started the short regimen and 18 patients eligible for the short regimen started the injectable-free individualized regimen. Overall, six-month smear and culture conversion were 98.7% and 97.1%, respectively; treatment success was 70.1%. Known initial fluoroquinolone resistance (aHR 3.77, 95%CI:1.53-9.27) but not choice of regimen predicted having an unfavourable outcome. Even though criteria for the choice of treatment regimen were not applied strictly, we have achieved acceptable outcomes in this cohort. To expand RR-TB care, treatment regimens should fit provision at primary health care level and take patient preferences into account.


Integration of photo-induced biocidal and hydrophilic antifouling functions on nanofibrous membranes with demonstrated reduction of biofilm formation.
Survival and pathogenic microbial adhesions on surfaces of materials followed by the formation of biofilms with robust resistance to antibiotics constitute the forefront of disease transmissions. Conventional strategies responding to this challenge are rather limited due to the biofouling effect of microorganisms or the irreversible consumption of antimicrobial agents embedded into the materials. Herein, we report an approach of combining photo-induced rechargeable biocidal properties with microbial resisting and releasing zwitterionic hydrophilic functions on surfaces of materials to improve antifouling performances. Poly(vinyl alcohol-co-ethylene) (EVOH) nanofibrous membranes (NFMs) were chemically incorporated with both 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BPTCD), a photoactive chemical, and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), a zwitterionic monomer. Both functional agents work independently and construct concerted microbial resisting, killing, and releasing functions to reduce microbial contamination and biofilm formation. The resulted SBMA@EVOH NFMs exhibited integrated features of large ROS production capacity, ease of photoactive rechargeability and controllability, long-term stability, high biocidal efficacy (>99.9999% via contact killing), and promising antifouling performance, which enable the SBMA@EVOH NFMs to serve as a biocidal material for food safety and medical applications.


Two distinct genomic regions, harbouring the period and fruitless genes, affect male courtship song in Drosophila montana.
Acoustic signals often have a significant role in pair formation and in species recognition. Determining the genetic basis of signal divergence will help to understand signal evolution by sexual selection and its role in the speciation process. An earlier study investigated quantitative trait locus for male courtship song carrier frequency (FRE) in Drosophila montana using microsatellite markers. We refined this study by adding to the linkage map markers for 10 candidate genes known to affect song production in Drosophila melanogaster. We also extended the analyses to additional song characters (pulse train length (PTL), pulse number (PN), interpulse interval, pulse length (PL) and cycle number (CN)). Our results indicate that loci in two different regions of the genome control distinct features of the courtship song. Pulse train traits (PTL and PN) mapped to the X chromosome, showing significant linkage with the period gene. In contrast, characters related to song pulse properties (PL, CN and carrier FRE) mapped to the region of chromosome 2 near the candidate gene fruitless, identifying these genes as suitable loci for further investigations. In previous studies, the pulse train traits have been found to vary substantially between Drosophila species, and so are potential species recognition signals, while the pulse traits may be more important in intra-specific mate choice.


Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan.
CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas. We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases. The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells. The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.


Lipoid proteinosis: pathognomonic clinical and radiological features.
A 22-year-old woman presented with a facial rash and hoarseness of voice. On examination, coarse waxy thickening and scarring was noted on the forehead and both the cheeks. The eyelid margins revealed a row of beaded papules termed 'moniliform blepharosis'. CT scan of the brain revealed bilateral, symmetric calcification of the amygdala of the hippocampal nuclei. This led to the diagnosis of lipoid proteinosis which is a rare genetic disorder.


Translocation of the umbilical artery to the lower abdomen: an adjunct to the postoperative monitoring of arterial blood gases in major abdominal wall defects.
A technique is presented for preserving the umbilical arteries for postoperative monitoring of arterial blood gases after repair of giant omphaloceles and gastroschisis. Translocation of the arteries to the lower abdominal wall removes them from the operative field and allows cannulation and long-term blood sampling. Complications have been minimal and the improved application of modern pulmonary support mechanisms has materially contributed to better patient management. The technique is a simple one and may prove applicable to other major newborn medical and surgical diseases involving respiratory insufficiency.


Development of an analytical method to determine avermectins in water, sediments and soils using liquid chromatography-tandem mass spectrometry.
A comprehensive analytical multi-residue method has been developed for the determination of seven avermectins (abamectin, doramectin, ivermectin, emamectin benzoate, eprinomectin, moxidectin and selamectin) in surface water, sediment and soil samples. Solid samples were extracted applying pressurised liquid extraction followed by a solid-phase extraction (SPE) clean-up step. For aqueous samples, extraction was done utilising only SPE. All compounds were measured using liquid chromatography coupled to tandem mass spectrometry using atmospheric pressure chemical ionisation. The recoveries were 38-67% (relative standard deviation: 9-26%), 63-88% (16-23%) and 63-80% (9-15%) for spiked Rhine water, spiked sediment and spiked soil samples, respectively, and limit of quantifications were 2.5-14 ngl(-1) in water and 0.5-2.5 ngg(-1) in soil and sediment.


Which neuromuscular attributes are most associated with mobility among older primary care patients?
To identify the neuromuscular attributes that are associated with self-reported mobility status among older primary care patients. Cohort study. Metropolitan-based health care system. Community-dwelling primary care patients aged ≥65 years (N=430), with self-reported modification of mobility tasks resulting from underlying health conditions. Not applicable. Basic and Advanced Lower Extremity Function as measured by the Late Life Function and Disability Instrument. We constructed multivariable linear regression models evaluating both outcomes. For Basic Lower Extremity Function, leg strength, leg velocity, trunk extensor muscle endurance, and ankle range of motion (ROM) were statistically significant predictors (P<.001, R(2)=.21). For Advanced Lower Extremity Function, leg strength, leg strength asymmetry, leg velocity, trunk extensor muscle endurance, and knee flexion ROM were statistically significant predictors (P<.001, R(2)=.39). Sensitivity analyses conducted using multiple imputations to account for missing data confirmed these findings. This analysis highlights the relevance and importance of 5 categories of neuromuscular attributes: strength, speed of movement, ROM, asymmetry, and trunk stability. It identifies novel attributes (leg velocity and trunk extensor muscle endurance) relevant to mobility and highlights that impairment profiles vary by the level of mobility assessed. These findings will inform the design of more thorough and potentially more effective disability prevention strategies.


Sarcopenia in patients with rheumatic musculoskeletal diseases.
To investigate the impact of high-dose glucocorticoid therapy on sarcopenia in hospitalized patients with rheumatic musculoskeletal diseases (RMDs). We included patients with RMDs who were hospitalized between 2020 and 2022 for remission induction treatment and collected information on skeletal mass index (SMI) before high-dose glucocorticoid therapy and 1 month later. We divided the patients into 2 groups according to the progression of sarcopenia, defined as a >10% decrease in SMI, and compared their clinical characteristics. Forty-nine patients were included in this analysis. The mean age was 53.3 years, 73.5% were female, and the mean SMI was 5.3 kg/m2 . Before treatment, 83.7% had already met the definition of sarcopenia, and 57.1% experienced further sarcopenia progression after 1 month of high-dose glucocorticoid treatment. Patients with sarcopenia progression were predominantly male (P = 0.025), had a higher body weight (P = 0.048), and showed a higher SMI than those without sarcopenia at baseline (P = 0.008). Multivariable analysis revealed that body weight increase from 0 to week 1 of high-dose glucocorticoid treatment was associated with sarcopenia progression (odds ratio: 0.22, 95% CI: 0.04-0.61, P = 0.007) with a cut-off of -1.8 kg. During a mean observation period of 30.2 days, the incidence of infection was significantly higher in patients with progressive sarcopenia (P = 0.042). One-month hospitalization with high-dose glucocorticoid therapy is associated with sarcopenia progression in patients with RMDs. An early decrease in body weight can be used to predict muscle volume loss.


[Histoautoradiographic study of thymidine-3H incorporation into the parenchymal nuclei of the kidneys and other organs in rats with nephrotoxic nephritis].
The features of changes in the index of thymidine-3H incorporation into the renal parenchyma in nephrotoxic nephritis are compared to other organs. In the kidneys the index of incorporation inthe epithelial cells of the renal cortex was 7.5-fold and in the brain cortex epithelium 15-fold as increased, respectively. The number of labeled glomerular cells was 2.5-fold as increased. In glomerulonephritis, the index of thymidine-3H incorporation in the epithelium of the adrenals, liver, goiter gland and small intestine lowered within 30-80% from normal.


Preliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin levels.
Ghrelin is a signal peptide isolated from rat stomach antagonistic to actions of leptin. Ghrelin stimulates the secretion of growth hormone (GH) and increases food intake, body mass, and adiposity in rodents. Photoperiod and melatonin regulate leptin secretion of mammals. The aim of the study was to investigate possible melatonin-ghrelin interactions in weight regulation by studying the effects of continuous pharmacologic melatonin treatment and constant light on plasma ghrelin, leptin, and GH levels in rats. Plasma ghrelin concentrations were significantly reduced by exogenous melatonin. Ghrelin levels correlated negatively with plasma leptin levels in control rats kept in 12 h of light/12 h of dark but not in the melatonin-treated animals. The inverse ghrelin-leptin relationship was also disrupted by constant illumination. The circulating ghrelin and GH levels may not be interrelated in all metabolic situations. The results suggest new interplay between the pineal gland and energy metabolism as well as reenforce the hypothesis that ghrelin is antagonistic to leptin.


A pilot study on staged surgery by delta video-assisted anal fistula treatment (dVAAFT) for complex anal fistula.
Complex anal fistulas (CAF) present a challenge in achieving healing while preserving anal sphincter function. This study aims to introduce a novel staged approach for CAF treatment, combining video-assisted anal fistula treatment (VAAFT), seton placement, and other staged approaches. Consecutive patients with CAF underwent the staged approach involving VAAFT and seton placement. Data on patient demographics, fistula characteristics, and operative findings were collected. Pre-operative work-up included clinical evaluation, endoanal ultrasonography (EAUS), and magnetic resonance imaging (MRI). Surgical techniques and outcomes were evaluated. Eighteen patients (median age 38 years) were included. Misplacement of a previously placed seton was observed in 64% of cases. VAAFT combined with seton placement achieved simplification and healing of secondary tracts in 66% of cases. Operative times significantly decreased across interventions. At a median follow-up of 14 months, complete healing was achieved in 2 patients, with 1 patient demonstrating persistence of the fistula. Post-operative complications were observed in 11% of patients, with no deterioration in continence. The staged approach combining VAAFT, seton placement, and staged procedures offers a potential solution for treating CAF. VAAFT provides diagnostic and therapeutic benefits, simplifying the fistula anatomy and optimizing seton placement. The approach allows subsequent procedures based on individual fistula characteristics.


An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder.
Previous work suggests that GET 73, a novel compound with putative activity on the metabotropic glutamate receptor subtype 5 (mGluR5), may represent a novel pharmacological treatment for alcohol use disorder (AUD). In this study, we investigated the safety, tolerability, pharmacokinetics, and biobehavioral effects of GET 73, when co-administered with alcohol, in individuals with alcohol dependence (AD). This was an inpatient, cross-over, randomized, double-blind, placebo-controlled, human laboratory study with non-treatment-seeking, alcohol-dependent individuals. The study used a within-subject design, with two counterbalanced stages, during which participants received GET 73 and then placebo, or vice versa. During each stage, participants underwent an alcohol interaction session and, on a separate day, an alcohol cue reactivity, followed by an alcohol self-administration session. Safety outcomes of GET 73 were excellent with no serious adverse events, nor adverse events of severe grade. The co-administration of alcohol and GET 73 did not affect the pharmacokinetics of GET 73 or alcohol. GET 73, compared to placebo, did not affect the alcohol-related stimulation effects, but increased the subjective sedative effects of alcohol. GET 73 did not affect alcohol cue-induced craving, or alcohol self-administration in the laboratory. The study confirms the safety and tolerability of GET 73 when co-administered with alcohol. Although, under this experimental condition, we did not detect an effect on alcohol craving and consumption in the laboratory, additional studies should be conducted administering GET 73 for an extended period in an outpatient setting.


Feasibility and efficiency of contrast enhanced ultrasound real time guided fine needle aspiration for sentinel lymph node of breast cancer.
To assess the feasibility and efficiency of contrast-enhanced ultrasound (CEUS) real-time guided fine needle aspiration (FNA) for sentinel lymph node (SLN) of breast cancer. This retrospective study reviewed 21 breast cancer patients who scheduled for surgical resection performed CEUS real-time guided SLN-FNA and intraoperative SLN biopsy (SLNB). The success rate of CEUS real-time guided SLN-FNA was analyzed. The FNA diagnostic efficiency of SLN metastasis was analyzed compared to SLNB. Twenty-six SLNs were detected by intradermal CEUS whereas 130 SLNs were detected by SLNB. The median SLNs detected by intradermal CEUS (n = 1) and by SLNB (n = 5) was significantly difference (p < 0.001). All 26 CE-SLNs of 21 patients were successfully performed intradermal CEUS dual image real-time guided SLN-FNA including 5 SLNs of 4 patients which were difficult to distinguish in conventional ultrasound. Compared to SLNB, FNA found 2 of 5 cases of SLN metastasis, the diagnosis sensitivity, specificity, positive predictive value, negative predictive value, false negative rate, false positive rate and Yoden index were 40%, 100%, 100%, 84.2%, 60%, 0%and 40%, respectively. SLN-FNA real-time guided by dual CEUS image mode was technically feasible. Patients with a positive SLN-FNA should be advised to ALND without intraoperative SLNB according to Chinese surgeon and patients' conservatism attitude. But a negative SLN-FNA did not obviate the need of conventional SLNB because of the high false negative rate.


The influence of a genetic change in egg production, body weight, fertility or response to cold stress on semen yield in the turkey.
Egg production and semen yield, sperm concentration and total sperm per ejaculate were positively associated in a line (E) selected for increased egg production. Semen yield was decreased in a line (F) selected for increased 16-week body weight in comparison to a randombred control population (RBC). The effect may be attributable to decreased egg production in this line, as another line (I), developed from the same RBC, which exhibited genetic increases in body weight but no reduction in egg production, did not differ significantly in semen yield from the RBC. Genetic increases in body weight reduced sperm concentration and total sperm per ejaculate. Genetic changes in average clutch length, total days lost from broodiness, fertility, and response to cold stress did not have a major influence on semen production in the turkey.


Reduction of serum Interleukin-1-like activity after treatment with dexamethasone.
The ability of steroids to modulate the appearance of Interleukin-1(IL-1) in vivo was evaluated in a model of endotoxin shock. High levels of IL-1 were found in serum from A/J mice which were sensitized with P. acnes and challenged with bacterial lipopolysaccharide (LPS). The factor appeared in the serum 2-4 hours after LPS challenge and was dependent on the period of P. acnes sensitization and the dose of LPS. Treating the mice with dexamethasone prior to LPS challenge resulted in significantly lower thymocyte proliferative activity in the serum. Three experiments demonstrated that this reduced activity reflects a decrease in IL-1. 1) The reduced activity was not due to the presence of proliferation inhibitors since mixing the serum from dexamethasone-treated mice with purified IL-1 or adding the equivalent amount of steroid directly to thymocyte cultures did not reduce the degree of proliferation. 2) When the serum was fractionated by gel filtration, the proliferative activity for both control and steroid treated sera eluted at 10-16 kilodaltons; however, the activity was nearly 50% less in the sample from steroid-treated mice. 3) In addition to thymocyte proliferative activity, IL-1 induces an increase in the serum titer of the acute phase protein known as serum amyloid A. Both serum- and gel-purified samples were able to induce the SAA, but again the samples from steroid-treated mice were much less active. We conclude that the factor produced in vivo has the properties of IL-1 and that the serum titre of the factor is reduced by dexamethasone treatment.


Long-term effect of estrogen replacement on plasma nitric oxide levels: results from the estrogen in the prevention of atherosclerosis trial (EPAT).
The estrogen in the prevention of atherosclerosis trial (EPAT) was a 2-year randomized controlled trial in which unopposed 17beta-estradiol reduced subclinical atherosclerosis progression, measured as change in carotid intima-media thickness (CIMT). This study was conducted to determine whether long-term 17beta-estradiol 1mg daily increased plasma nitric oxide (NO) levels and whether this accounted for atheroprotection in EPAT. Although the on-trial serum estradiol level was significantly higher in the estradiol-treated group (n = 91 subjects) than the placebo group (n = 89 subjects) (mean (S.D.) = 59.0 (31.7) pg/ml versus 14.3 (10.4) pg/ml, p < 0.0001), there was no significant difference in the on-trial plasma NO levels, 18.5 (8.2) microM versus 20.1 (9.3) microM. Correlation between on-trial estradiol level and NO change was -0.22 (p = 0.003) in the total sample (placebo- and estradiol-treated subjects) and -0.21 (p = 0.049) in the estradiol-treated group. Change in NO levels was inversely correlated to change in LDL-cholesterol in the estradiol group (r = -0.23, p = 0.03). An NO response to 17beta-estradiol according to age, time since menopause and baseline CIMT was not found arguing against a possible NO effect in healthy versus diseased endothelium. NO levels were not related to CIMT progression. In this study, we found no evidence for an estrogen-induced effect on plasma total NO levels which unlikely accounted for the mechanism underlying the 17beta-estradiol atheroprotective effect on subclinical atherosclerosis progression.


The autophagy enhancer spermidine reverses arterial aging.
Arterial aging, characterized by stiffening of large elastic arteries and the development of arterial endothelial dysfunction, increases cardiovascular disease (CVD) risk. We tested the hypothesis that spermidine, a nutrient associated with the anti-aging process autophagy, would improve arterial aging. Aortic pulse wave velocity (aPWV), a measure of arterial stiffness, was ~20% greater in old (O, 28 months) compared with young C57BL6 mice (Y, 4 months, P<0.05). Arterial endothelium-dependent dilation (EDD), a measure of endothelial function, was ~25% lower in O (P<0.05 vs. Y) due to reduced nitric oxide (NO) bioavailability. These impairments were associated with greater arterial oxidative stress (nitrotyrosine), superoxide production, and protein cross-linking (advanced glycation end-products, AGEs) in O (all P<0.05). Spermidine supplementation normalized aPWV, restored NO-mediated EDD and reduced nitrotyrosine, superoxide, AGEs and collagen in O. These effects of spermidine were associated with enhanced arterial expression of autophagy markers, and in vitro experiments demonstrated that vascular protection by spermidine was autophagy-dependent. Our results indicate that spermidine exerts a potent anti-aging influence on arteries by increasing NO bioavailability, reducing oxidative stress, modifying structural factors and enhancing autophagy. Spermidine may be a promising nutraceutical treatment for arterial aging and prevention of age-associated CVD.


Embryonal tumors in the adult population: implications in therapeutic planning.
The natural history of neuroectodermal tumors is still debated as far as prognostic factors are concerned; the same uncertainty applies to the optimal radiotherapy schedule and even more to the presumptive additive effect of chemotherapy. The rarity of these tumors and the heterogeneity of management make interpretation of literature data also more difficult. We evaluated clinical course in a cohort of 39 patients, including 31 with medulloblastoma (MB) and 8 with primitive neuroectodermal tumors (PNET). All patients were treated with radiotherapy, a standardized chemotherapy protocol including PCV scheme, and a second-line chemotherapy with cisplatin and etoposide (VP16) at recurrence. In 27 patients, intrathecal chemotherapy was also delivered. Median follow-up was 10.8 years. Overall, PNET had a worse outcome as compared to MB: median survival times were 42.8 vs. 92.6 months, respectively (p = 0.05). At 5 years, 45% of MB patients are alive. No significant difference in disease-free period was found between patients of different age, desmoplastic variant, tumor localization, or extent of surgery. Patients considered to be "high risk" had a significantly shorter disease-free period as compared with low-risk patients (27 vs. 54.7 months, p = 0.04). Systemic or intrathecal chemotherapy did not influence progression-free survival (PFS). However, in the majority of chemotherapy-treated patients, a low-dose craniospinal radiotherapy was also delivered. This combination of treatments may have avoided the expected increased percentage of failure. Moreover, more than half of recurrent patients had a partial response to chemotherapy that extended survival for approximately 3 years. Repeated surgery and chemotherapy at recurrence favorably influenced survival time.


Mononuclear phagocytes in the blood of turtles characterized by ultrastructural and cytochemical analyses and by phagocytic activity.
Ultrastructural and cytochemical characteristics of mononuclear phagocyte cells in turtles are not well described in the literature, especially in Phrynops hilarii. Thus, the aim of this study was to evaluate these characteristics in the mononuclear phagocyte cells and their phagocytic activity "in vitro" using the turtle P. hilarii as an experimental animal model. The six turtles used in the study were observed in two seasons, spring and summer. Results showed that mononuclear phagocytes incubated only in diluted solution or with colloidal charcoal have cytoplasm phagolysosomes. The cells incubated with colloidal charcoal and further exposed to the cytochemical reaction for acid beta-glycerophosphatase, showed cytoplasm phagolysosomes filled by charcoal particles being digested and some positively stained lysosomes. Acid beta-glycerophosphatase positive reaction was present in lysosomes and inside the phagolysosomes, while acid cytidine 5-monophosphatase staining occurred in lysosome surroundings. A positive reaction for trimetaphosphatase was also found inside phagolysosomes. In conclusion, the presence of lysosomal enzymes like trimetaphosphatase and cytidine-5'-sodium monophosphate, in the circulating blood of P. hilarii indicate that mononuclear phagocytes participate in the phagocytic process by gathering many phagocytic cells and forming multinucleated giant cells, which probably have a role in the blood "clearance" process.


Osteogenesis Promotion of Selenium-Doped Hydroxyapatite for Application as Bone Scaffold.
The combined bioceramic of selenium (Se) and hydroxyapatite (HA) has been considered as a moderate bone scaffold biomaterial. In the present work, Se was doped into the HA structure using the mechano-chemical alloying (MCA) method for the improvement of osteogenic properties of HA. HA extracted from fish bone and Se-doped hydroxyapatite (Se-HA) were analyzed using X-ray diffraction spectra (XRD), scanning electron microscope (SEM), energy dispersion X-ray spectrometer (EDX), and Fourier transform infrared spectroscopy (FT-IR). In-vitro cell responses on the Se-HA bioceramic scaffold were investigated using human adipose-derived mesenchymal stem cells (hAD-MSCs). The effect of Se on cell proliferation was studied by MTT assay, and cell adhesion responses were analyzed by optical microscopy and SEM. Furthermore, the effect of Se on osteogenic properties of HA was studied by alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and Western blot tests. The MTT results showed that the Se dopant synergistically increases the proliferation of hAD-MSCs. Moreover, good cell-adhesive and osteoblast-shaped behaviors were observed on the Se-HA scaffold. The results of osteogenic differentiation demonstrated synergistically enhanced ALP activity and calcification on the Se dopant compared to HA. Also, the results of Western blot test presented that the differentiation of hAD-MSCs toward being a bone tissue was increased by up to 50% while selenium doping. Additional MTT analysis using Human Bone Osteosarcoma cell line (KHOS-240S) revealed the antiproliferative activity of the Se-HA scaffold against bone cancerous cells. Therefore, it has been concluded that Se-HA bioceramic can be employed as a scaffold with simultaneous anticancer and bone regenerative properties.


A comparison of direct brush cytology and biopsy in the diagnosis of colorectal cancer.
Direct brush cytology has been underutilized as compared with direct biopsy in the endoscopic diagnosis of colorectal lesions. We report on a large series of patients in whom biopsy and brush cytology were compared with each other and with the pathology of the specimen. Our results show that cytology should be used with biopsy to get maximal yield (97% accuracy), especially in areas of strictures or obstruction.


Performance of polarization-sensitive neurons of the locust central complex at different degrees of polarization.
The polarization pattern of the sky is exploited by many insects for spatial orientation and navigation. It derives from Rayleigh scattering in the atmosphere and depends directly on the position of the sun. In the insect brain, the central complex (CX) houses neurons tuned to the angle of polarization (AoP), that together constitute an internal compass for celestial navigation. Polarized light is not only characterized by the AoP, but also by the degree of polarization (DoP), which can be highly variable, depending on sky conditions. Under a clear sky, the DoP of polarized sky light may reach up to 0.75 but is usually much lower especially when light is scattered by clouds or haze. To investigate how the polarization-processing network of the CX copes with low DoPs, we recorded intracellularly from neurons of the locust CX at different stages of processing, while stimulating with light of different DoPs. Significant responses to polarized light occurred down to DoPs of 0.05 indicating reliable coding of the AoP even at unfavorable sky conditions. Moreover, we found that the activity of neurons at the CX input stage may be strongly influenced by nearly unpolarized light, while the activity of downstream neurons appears less affected.


EphrinB-EphB receptor signaling contributes to bone cancer pain via Toll-like receptor and proinflammatory cytokines in rat spinal cord.
Treating bone cancer pain poses a major clinical challenge, and the mechanisms underlying bone cancer pain remain elusive. EphrinB-EphB receptor signaling may contribute to bone cancer pain through N-methyl-d-aspartate receptor neuronal mechanisms. Here, we report that ephrinB-EphB signaling may also act through a Toll-like receptor 4 (TLR4)-glial cell mechanism in the spinal cord. Bone cancer pain was induced by tibia bone cavity tumor cell implantation (TCI) in rats. TCI increased the expression of TLR4 and the EphB1 receptor, the activation of astrocytes and microglial cells, and increased levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The increased expression of TLR4 and EphB1 were colocalized with each other in astrocytes and microglial cells. Spinal knockdown of TLR4 suppressed TCI-induced behavioral signs of bone cancer pain. The TCI-induced activation of astrocytes and microglial cells, as well as the increased levels of IL-1β and TNF-α, were inhibited by intrathecal administration of TLR4-targeting siRNA2 and the EphB receptor antagonist EphB2-Fc, respectively. The administration of EphB2-Fc suppressed the TCI-induced increase of TLR4 expression but siRNA2 failed to affect TCI-induced EphB1 expression. Intrathecal administration of an exogenous EphB1 receptor activator, ephrinB2-Fc, increased the expression of TLR4 and the levels of IL-1β and TNF-α, activated astrocytes and microglial cells, and induced thermal hypersensitivity. These ephrinB2-Fc-induced alterations were suppressed by spinal knockdown of TLR4. This study suggests that TLR4 may be a potential target for preventing or reversing bone cancer pain and other similar painful processes mediated by ephrinB-EphB receptor signaling.


Determination of 3β-hydroxy-Δ5-bile acids and related compounds in biological fluids of patients with cholestasis by liquid chromatography-tandem mass spectrometry.
A method for the determination of conjugated and unconjugated 3β-hydroxy-Δ5-bile acids and related bile acids in human urine and serum has been developed using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry. Calibration curves for the bile acids were linear over the range of 10 2000 pmol/mL, and the detection limit was less than 4 pmol/mL for all bile acids using selected reaction monitoring analysis. The bile acids in urine and serum samples from two patients with severe cholestatic liver disease were measured by this analytical method. Glycine-conjugated 3β-hydroxy-Δ5-bile acid 3-sulfates were determined to be the major bile acids in the urine and serum from patients with a 3β-hydroxy-Δ5-C27-steriod dehydrogenase/isomerase deficiency or dysfunction.


Hydroxyl-directed conjugate additions of carbon nucleophiles to cyclopentadienones.
[Structure: see text] The conjugate additions of different carbon nucleophiles to cyclopentadienone substrates (1 and 2) with one free hydroxyl functional group were investigated to determine the role of the hydroxyl group in controlling regiochemistry. During this reaction an unexpected intramolecular displacement of OTBS by the enolate intermediate occurs, to afford cyclopropane derivatives.


Glucose transformation to 5-hydroxymethylfurfural in acidic ionic liquid: A quantum mechanical study.
Isomerization and transformation of glucose and fructose to 5-hydroxymethylfurfural (HMF) in both ionic liquids (ILs) and water has been studied by the reference interaction site model self-consistent field spatial electron density distribution (RISM-SCF-SEDD) method coupled with ab initio electronic structure theory, namely coupled cluster single, double, and perturbative triple excitation (CCSD(T)). Glucose isomerization to fructose has been investigated via cyclic and open chain mechanisms. In water, the calculations support the cyclic mechanism of glucose isomerization; with the predicted activation free energy is 23.8 kcal mol(-1) at experimental condition. Conversely, open ring mechanism is more favorable in ILs with the energy barrier is 32.4 kcal mol(-1) . Moreover, the transformation of fructose into HMF via cyclic mechanism is reasonable; the calculated activation barriers are 16.0 and 21.5 kcal mol(-1) in aqueous and ILs solutions, respectively. The solvent effects of ILs could be explained by the decomposition of free energies and radial distribution functions of solute-solvent that are produced by RISM-SCF-SEDD.


Celastrol ameliorates autoimmune disorders in Trex1-deficient mice.
Celastrol is one of most potent bioactive molecule isolated from the medicinal plant Tripterygium wilfordii (Thunder God Vine) and is well known for its potential therapeutic value against various chronic diseases including the autoimmune diseases, such as systemic lupus erythematosus and Aicardi-Goutieres syndrome, or other interferonopathies. However, the underlying mechanism of celastrol function remains unclear. Here we showed that celastrol caused inhibition of interferon regulatory factor 3 (IRF3) activation leading to the down-regulation of the interferon response triggered by cytosolic nucleic acids in vitro and in vivo. Moreover, celastrol treatment markedly ameliorates the autoimmune phenotypes including myocarditis, aberrant interferon response and autoantibody production, as well as the excessive T-cell activation in Trex1-/- autoimmune disease mouse model. Collectively, our results indicate that celastrol inhibits interferon response by targeting IRF3 activation and may be used as an effective treatment for interferon response-dependent autoimmune diseases.


Hepatectomy for huge primary liver cancer: report of 171 patients.
To discuss the safety and feasibility of hepatectomy for huge primary liver cancer (PLC). The effect of resection of huge PLC was examined retrospectively. Some problems about resection of huge PLC were discussed. In 171 patients with huge PLC undergoing hepatectomy, 2 (1.2%) died in one month after operation. The 1-, 2-, 3-, 5- and 10-year survival rates of the patients were 66.1%, 42.1%, 32.7%, 12.2% and 2.3%, respectively. The effect of prolonging survival time was significant. Hepatectomy for huge PLC is safe, feasible, and effective.


Postural balance under normal and altered sensory conditions in normal-weight and overweight children.
little or no research has been done in the overweight child on the relative contribution of multisensory information to maintain postural stability. Therefore, the purpose of this study was to investigate postural balance control under normal and experimentally altered sensory conditions in normal-weight versus overweight children. sixty children were stratified into a younger (7-9yr) and an older age group (10-12yr). Participants were also classified as normal-weight (n=22) or overweight (n=38), according to the international BMI cut-off points for children. Postural stability was assessed during quiet bilateral stance in four sensory conditions (eyes open or closed, normal or reduced plantar sensation), using a Kistler force plate to quantify COP dynamics. Coefficients of variation were calculated as well to describe intra-individual variability. removal of vision resulted in systematically higher amounts of postural sway, but no significant BMI group differences were demonstrated across sensory conditions. However, under normal conditions lower plantar cutaneous sensation was associated with higher COP velocities and maximal excursion of the COP in the medial-lateral direction for the overweight group. Regardless of condition, higher variability was shown in the overweight children within the 7-9yr old subgroup for postural sway velocity, and more specifically medial-lateral velocity. in spite of these subtle differences, results did not establish any clear underlying sensory organization impairments that may affect standing balance performance in overweight children compared to normal-weight peers. Consequently, it is believed that other factors account for overweight children's functional balance deficiencies.


Genetically engineered biosynthetic pathways for nonnatural C60 carotenoids using C5-elongases and C50-cyclases in Escherichia coli.
While the majority of the natural carotenoid pigments are based on 40-carbon (C40) skeleton, some carotenoids from bacteria have larger C50 skeleton, biosynthesized by attaching two isoprene units (C5) to both sides of the C40 carotenoid pigment lycopene. Subsequent cyclization reactions result in the production of C50 carotenoids with diverse and unique skeletal structures. To produce even larger nonnatural novel carotenoids with C50 + C5 + C5 = C60 skeletons, we systematically coexpressed natural C50 carotenoid biosynthetic enzymes (lycopene C5-elongases and C50-cyclases) from various bacterial sources together with the laboratory-engineered nonnatural C50-lycopene pathway in Escherichia coli. Among the tested enzymes, the elongases and cyclases from Micrococcus luteus exhibited significant activity toward C50-lycopene, and yielded the novel carotenoids C60-flavuxanthin and C60-sarcinaxanthin. Moreover, coexpression of M. luteus elongase with Corynebacterium cyclase resulted in the production of C60-sarcinaxanthin, C60-sarprenoxanthin, and C60-decaprenoxanthin.


Ultrastructural and autoradiographic observations of hamster cheek pouch epithelium grown in vitro.
Epithelial outgrowths from hamster cheek pouch explants were cultured for varying periods of time up to 22 days. Growth of the epithelial sheets was monitored, employing colcemid for demonstrating mitotic activity and tritiated thymidine for DNA synthesis. Mitoses and thymidine uptake were observed among epithelial outgrowths at a considerable distance form the original explant. The epithelial nature of the growing cell sheets was confirmed, employing electron microscopic techniques. The cells exhibited the presence of tonofilaments, desmosomes, ribosomes, Golgi, mitochondria, and rough endoplasmic reticulum. The cultured explants were treated with cyclic nucleotides in order to investigate their modulatory effects on epithelial cell differentiation. Dibutyryl cAMP induced marked mitotic inhibition (46.3%) in our assay, which was increased to 57% with the addition of theophylline. Dibutyryl cGMP showed only a mild (5%) stimulatory effect on mitotic activity. Dibutyryl cAMP enhanced keratinization in the epithelial cell outgrowths with the biogenesis of keratohyalin granules, whereas dibutyryl cGMP did not produce any observable alterations.


Impact of portal-phase signal intensity of dynamic gadoxetic acid-enhanced magnetic resonance imaging in hepatocellular carcinoma.
To evaluate the prognostic impact of dynamic gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC). We retrospectively reviewed the data of 206 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI and hepatectomy and quantitatively evaluated the signal intensity ratio of the tumor to the surrounding liver tissue in the portal phase (SIRPP). We verified the survival rates and assessed the prognostic factors associated with overall survival (OS) and recurrence-free survival (RFS) using SIRPP. Multivariate analysis revealed that the independent predictive factors for poorly-differentiated HCC were α-fetoprotein > 20 ng/mL (hazard ratio [HR]: 3.1909, 95% confidence interval [CI]: 1.3464-7.5622, p = .0084) and SIRPP ≤ 0.85 (HR: 3.7155, 95% CI: 1.521-9.076, p = .004). The 5-year OS and RFS rates in the high and low SIRPP groups were 83.2 and 52.1%, respectively (p < .0001) and 49.7 and 18.5%, respectively (p = .0003). Multivariate analysis revealed that SIRPP ≤ 0.68 was an independent prognostic factor related to OS (HR: 4.4537, 95% CI: 1.6581-11.9626, p = .003). The SIRPP of preoperative Gd-EOB-DTPA-enhanced MRI might predict the histological differentiation and prognosis of HCC.


Pain management: the veterinary technician's perspective.
In veterinary medicine, technicians provide primary nursing care and function as patient advocates. In this role, veterinary technicians have great influence over animal pain management. This article focuses on assessing patients for comfort, providing appropriate nonpharmacologic and pharmacologic therapy, and general concepts of providing optimal analgesia. The communication necessary for successful implementation of pain management strategies is discussed in detail.


Mitochondrial uncoupling protein 1 expression in thymocytes.
Using an antibody specific and selective to mitochondrial uncoupling protein 1 (UCP1) peptide, this study confirms the observation that UCP 1 is present in thymocytes isolated from UCP 1 wild-type, but not UCP 1 knock-out mice. UCP 1 is also shown to be present in thymocytes isolated from rat. It was also demonstrated that an antibody raised to the full-length UCP 1 protein appears to be non-specific for UCP 1, as it detects protein in UCP 1 wild-type and UCP 1 knock-out mice, protein in mitochondria isolated from brown adipose tissue of both UCP 1 wild-type and UCP 1 knock-out mice, as well as detecting protein in mitochondria isolated from rat spleen, kidney, skeletal muscle and liver, tissues that do not express UCP 1. We were also able to show that CIDEA, a soluble protein with a suggested role in regulating UCP 1 function, is equally abundant in thymocytes from UCP 1 wild-type and UCP 1 knock-out mice. Taken together our data demonstrate that (a) UCP 1 is present in rat and mouse thymocytes, (b) that the antibody to full-length UCP 1 is not specific for UCP 1 and (c) that the absence of UCP 1 does not affect native expression of CIDEA in thymocytes.


Does cyclic GMP mediate amylase release from mouse parotid acini?
In mouse parotid acini both cholinergic and beta-adrenergic agonists increased intracellular levels of cyclic-GMP (c-GMP) as well as amylase release. The derivative of c-GMP, 8-bromo-c-GMP, mimicked the effects of cholinergic and beta-adrenergic stimulation on amylase release. Nitroprusside (NP), hydroxylamine (HA) and sodium azide (NaA) increased c-GMP levels and also enhanced amylase release in a dose-dependent manner; cyclic-AMP (c-AMP) levels were not affected. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (MIX) enhanced the effects of carbachol on both c-GMP accumulation and amylase release. These results suggest that c-GMP may mediate the actions of cholinergic agonists and at least partially mediate the actions of beta-adrenergic agonists on mouse parotid enzyme release.


A Retrospective Database Study of Liraglutide Persistence Associated with Glycemic and Body Weight Control in Patients with Type 2 Diabetes.
In both randomized controlled trials and real-world studies, liraglutide has demonstrated glycemic and body weight benefits in patients with type 2 diabetes. However, persistence with diabetes medication can be challenging. This study compared glycated hemoglobin (HbA1c) and other outcomes in patients with type 2 diabetes who continued treatment with liraglutide for over 12 months with those who discontinued treatment earlier, in a real-life setting. This is a retrospective study of adult patients with type 2 diabetes from Maccabi Healthcare Services in Israel, who initiated treatment with liraglutide from 2010 to 2015. Mean HbA1c and body weight change from initiation to after 24 months was compared between patients who received liraglutide for at least 12 months ("continuers") and those who discontinued within the first year ("discontinuers"). Adjustment for HbA1c, body weight, and other potentially confounding factors was performed using 1:1 propensity score matching. The 3580 patients comprised 2695 continuers and 885 discontinuers; 882 patients per group were matched. A significant (p < 0.001) reduction in HbA1c (- 0.80% vs - 0.32%) was seen in continuers compared with discontinuers, despite higher insulin usage (70.2% vs 59.0%; p < 0.001), and a higher proportion of patients using ≥ 3 oral glucose-lowering drugs (20.6% vs 6.2%; p < 0.001) at 24 months among discontinuers. Mean body weight reduction was greater in continuers than discontinuers (3.57 vs 1.25 kg; p < 0.001). In a real-world setting, persistent use of liraglutide was associated with good glycemic and body weight control. Novo Nordisk Health Care AG.


Cryptosporidium species from human immunodeficiency-infected patients with chronic diarrhea in Jakarta, Indonesia.
Cryptosporidium is an opportunistic parasite that manifests as chronic and severe diarrhea in the immune-compromised subject. We investigated the species of Cryptosporidium to understand the epidemiology, mode of transmission, response to treatment, and prevention. Polymerase chain reaction/restriction fragment length polymorphism of the 18 S rRNA gene and sequencing were performed on 41 Cryptosporidium-positive stools from 36 patients with HIV AIDS, which comprised 36 pretreatment stools and 5 stools after treatment with Paromomycin. C. hominis, C. meleagridis, C. felis, and C. parvum were detected; 28 of 36 (77.7%) patients were infected with C. hominis and two (5.5%) patients with multiple species of Cryptosporidium. Treatment with Paromomycin resulted in different outcomes, perhaps because patients harbored other intestinal parasitic infections. Multiple infection with various Cryptosporidium species in the presence of other intestinal parasites occurs in patients with HIV AIDS suffering from chronic diarrhea who are severely immune-compromised. Common transmission of Cryptosporidium is anthroponotic.


Incentive delivery timing and follow-up survey completion in a prospective cohort study of injured children: a randomized experiment comparing prepaid and postpaid incentives.
Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study's objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.


Panic-fear in asthma: a divergence between subjective report and behavioral patterns.
The reported frequency of occurrence of Panic-Fear symptoms during asthmatic attacks varies widely and is related to treatment response independently of the objective severity of asthma. In a previous study, symptom minimizers (Low Panic-Fear) requested few as-needed (PRN) medications and treatments while hospitalized, even on days when significant airway obstruction was present. In contrast symptom emphasizers (High Panic-Fear) requested PRNs frequently, even on days when no airway obstruction was present. In the present study, these behavioral differences toward PRNs occurred despite the similar ability of patients in various Panic-Fear groups to perceive and report changes in airway obstruction. Together these results suggest that specific behavioral strategies, which do not derive from differences in symptom perception, influence the treatment response of asthmatic patients differing in Panic-Fear symptomatology.


Different inhibitory mechanisms of chlortetracycline and enrofloxacin on mesophilic anaerobic degradation of propionate.
In anaerobic digestion, propionate is a key intermediate whose degradation is thermodynamically challenging and accumulation is detrimental to the process. Many wastewater streams contain antibiotics due to its globally increasing use, and these compounds can inhibit methane production. However, the effect of antibiotics on propionate degradation in anaerobic digestion remains unclear. In this study, the influence of two antibiotics (chlortetracycline [CTC] and enrofloxacin [EFX]) on biogas production and mesophilic propionate-degrading microbial community was investigated. CTC strongly repressed propionate oxidation, acetate utilization, and methane production, while EFX only inhibited propionate oxidation and methane production to a lesser extent. Microbial community analyses showed that syntrophic propionate-oxidizing bacteria (SPOB) Syntrophobacter had strong tolerance to both CTC and EFX. CTC inhibition mainly acted on the activity of acetate-oxidizing bacteria (Mesotoga, Geovibrio, Tepidanaerobacter, unclassified Bacteroidetes, and unclassified Clostridia) and acetoclastic methanogen, while EFX inhibition applied to the SPOB Smithella and acetoclastic methanogen. Network analysis further indicated that more complicated correlation among bacterial genera occurred in CTC treatments. These results suggested that CTC and EFX inhibited propionate degradation via different mechanisms, which was the result of joint action by antibiotics and microbial interactions.


Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery.
To determine whether using topical vancomycin powder in fracture surgery may result in low levels of vancomycin in the serum and not result in nephrotoxicity. Prospective observational at a single site as a substudy of the VANCO trial. Single, large urban level I trauma center. Fifty-eight patients with tibial plateau and pilon fractures randomized to the treatment arm at the principal investigator's site. Topical vancomycin powder (1000 mg) applied directly in the wound over all metal implants at the time of wound closure. Serum vancomycin levels at 1 hour and 6-8 hours after surgery. Secondary outcomes included serum creatinine before surgery, a day after surgery, and at 2 weeks postoperatively and complete blood count at 2 weeks postoperatively. Except in 2 patients who also received intravenous vancomycin, none of the study patients had detectable (>5 µg/mL) serum vancomycin levels at 1 hour and 6-8 hours after surgery. One patient with a history of elevation of serum creatinine had a minor increase of serum creatinine but had undetectable vancomycin levels. None of the other patients had a clinically significant increase in creatinine levels. Despite its relatively widespread usage, little data exist regarding the systemic levels and nephrotoxicity associated with the topical use of vancomycin powder in orthopaedic fracture surgery. These prospective data indicate that there seems to be little clinical concern regarding toxicity associated with systemic absorption of vancomycin powder in this specific clinical application. Therapeutic Level IV. See instructions for authors for a complete description of levels of evidence.


From successful measurement to the birth of a law: Disentangling coordination in Ohm's scientific practice.
In this paper, I argue for a distinction between two scales of coordination in scientific inquiry, through which I reassess Georg Simon Ohm's work on conductivity and resistance. Firstly, I propose to distinguish between measurement coordination, which refers to the specific problem of how to justify the attribution of values to a quantity by using a certain measurement procedure, and general coordination, which refers to the broader issue of justifying the representation of an empirical regularity by means of abstract mathematical tools. Secondly, I argue that the development of Ohm's measurement practice between the first and the second experimental phase of his work involved the change of the measurement coordination on which he relied to express his empirical results. By showing how Ohm relied on different calibration assumptions and practices across the two phases, I demonstrate that the concurrent change of both Ohm's experimental apparatus and the variable that Ohm measured should be viewed based on the different form of measurement coordination. Finally, I argue that Ohm's assumption that tension is equally distributed in the circuit is best understood as part of the general coordination between Ohm's law and the empirical regularity that it expresses, rather than measurement coordination.


Flunitrazepam induces neurotoxicity in zebrafish through microbiota-gut-brain axis.
The abuse of psychoactive substances has led to their frequent detection in the environment, with unknown effects on the nervous system. In this study, zebrafish were exposed to benzodiazepine drug flunitrazepam (FLZ, 0.2 and 5 μg/L) for 30 days to assess its neurotoxicity. Results revealed that FLZ disrupted the balance of gut microbiota and caused an increase in pathogenic bacteria, such as Paracoccus and Aeromonas, leading to pathological damage to the intestine. The upregulation of intestinal pro-inflammatory factors, IL-1β and TNF-α, by 2.4 and 6.3 times, respectively, along with the downregulation of tight junction proteins, Occludin and zonula occludens 1 (ZO-1), by 80 % and 50 %, increased in intestinal permeability. Moreover, untargeted metabolomics demonstrated that FLZ interfered with intestinal nucleotide metabolism and amino acid biosynthesis. FLZ could also increase the levels of lipopolysaccharide (LPS) and malondialdehyde (MDA) in the brain by 0.9 and 3.4 times, respectively, leading to pathological changes in brain tissue. Furthermore, FLZ significantly disturbed nucleotide metabolism and amino acid biosynthesis and metabolism pathways in the brain. Correlation analysis between gut microbiota and neurochemicals confirmed that FLZ can induce neurotoxicity through the microbiota-gut-brain axis. These findings elucidate the molecular mechanisms of psychoactive drugs on microbiota-gut-brain axis and provide a theoretical basis for the ecological environmental risk assessment of various psychoactive substances.


Effect of cell culture on rabbit colonic smooth muscle bradykinin receptors.
The aim of this study was to assess the effect of cell culture on the bradykinin receptor of rabbit colon myocytes. In longitudinal muscle strips prepared from distal colon, bradykinin stimulated dose-dependent contraction that was 62% of the maximal response to bethanecol. At 4 degrees C, [3H]bradykinin binding to fresh muscle homogenates from the distal colon was time dependent, saturable, and linearly related to tissue concentration. Specific binding of 0.6 nmol/L [3H]bradykinin was 80% +/- 2% of total binding. In competitive binding studies, Hill coefficients approached unity, suggesting the presence of a single class of receptors. The order of potency was bradykinin greater than [D-Phe7]bradykinin much greater than des-Arg9, [Leu8]bradykinin, which is consistent with results of a B2 receptor subclass. Colon myocytes from the longitudinal muscle layer achieved confluence and were harvested for studies after 12-14 days in culture. Bradykinin receptors were of high affinity [disassociation constant (Kd) = 672 pmol/L] and numbered 10,217 +/- 2567/cell. To show that the receptors on cultured myocytes were functional, the effect of bradykinin was measured (a) on intracellular calcium concentration using Fura 2 and (b) on prostaglandin E2 concentration in the culture media using radioimmunoassay. In cells grown to confluence on cover slips and preloaded with Fura 2, bradykinin stimulated the threshold response at 1 nmol/L and maximal response (increased intracellular calcium concentration from 229 to 633 nmol/L) at 1 mumol/L. Bradykinin, 100 nmol/L, increased Prostaglandin E2 in the culture media threefold. In summary, colon myocytes express functioning bradykinin receptors, which, unlike muscarinic receptors, persist in culture. Bradykinin appears to be a suitable agonist for studies of receptor-mediated intracellular events in cultured colon myocytes.


Strengthening the service continuum between transfusion providers and suppliers: enhancing the blood services network.
As the cost of health care increases, the focus on cost containment grows. The pressure to reduce costs comes at the same time the public focus is on ensuring a zero-risk blood supply. The blood supply has never been safer or more expensive. With the relative vanquishing of transfusion-transmitted diseases, noninfectious risks now exceed infectious risks. This has resulted in a call to refocus blood safety efforts on interconnected processes that link a unit of blood from its volunteer blood donor to the patient. Additional costs in the blood supply chain will create new pressures on an already taxed system that gets little additional reimbursement with each new safety initiative. Opposing interests have created a tenuous relationship between the blood supplier and the transfusion provider. This adversarial relationship does not benefit the ultimate stakeholder, the patient. It is time to create a service partnership that is built on access, cost, and quality. Initiatives must be undertaken at a local, regional, and national level. Locally, blood suppliers and transfusion providers must reevaluate policies that are focused on individual gain and reinvent policies that will reward improvements in the overall system and expand cooperative services. Regionally, both blood suppliers and transfusion providers need to consolidate services to gain cost and quality benefits without compromising the competitive nature of the industry. Nationally, the creation of a strategic plan will help ensure that a mutually beneficial relationship focused on the patient is created between the blood supplier and transfusion provider at all levels. Development of such a plan would benefit the transfusing and supplying parties by identifying areas of common interest and how each may facilitate the achievement of shared benefits.


How COVID-19 pandemic affected medical waste management in Türkiye.
The COVID-19 pandemic has caused an increase in medical waste in hospitals. To evaluate how the COVID-19 pandemic is affecting medical waste management in hospitals in Isparta Province, south-western Türkiye. We examined medical waste production in 3 different types of hospital (1 private, 1 public and 1 university) in Isparta Province, south-western Türkiye. We compared the number of patients, amount of medical waste and occupancy rates of the 3 hospitals during the pre-pandemic (2019-2020) and pandemic (2020-2021) periods. The data were analysed using SPSS, version 22.0, and statistical significance was set at P < 0.05. During the pandemic, the number of inpatients in the public and university hospitals decreased, while the number in the private hospital increased. The amount of medical waste during the pre-pandemic period was 8.4 kg per person in the public hospital, 7.7 kg per person in the university hospital and 6.3 kg per person in the private hospital. During the pandemic, these amounts were 14.2 kg, 10.1 kg and 7.6 kg per person, respectively. There was a significant increase in medical waste during the COVID-19 pandemic. Health institutions in Isparta Province, Türkiye, need to review their medical waste management strategies to better manage the increased waste.


Gastroesophageal reflux in athletes.
Gastroesophageal reflux (GER) and its associated symptoms are common among athletes. In the athlete, GER increases with intensity of exercise, is more common with endurance sports, and worse with postprandial exercise. GER has symptoms that overlap with other upper gastrointestinal (GI) conditions. Symptoms of GER can be difficult to distinguish from cardiac chest pain. GER may exacerbate asthma. Proposed mechanisms causing GER during exertion include altered GI blood flow and motor function, neuroendocrine changes, and mechanical effects. GER symptoms that interfere with activity may respond to lifestyle modification or pharmacologic therapy.


Single charge exchange in collisions of energetic nuclei with biomolecules of interest to ion therapy.
This study is on the theory of single electron capture by fast nuclei from a variety of molecular targets of biological significance with high relevance to ion therapy of deep-seated tumors. The adopted theoretical framework is that of the first principles of quantum physics. As such, no free, adjustable parameters are used. This is in sharp contrast to the associated existing cross section input data to Monte Carlo simulations that all abound with empirical/phenomenological formulae. The present theory has the well-established track of its predictive power. This means that the computed cross sections can confidently be used in the cases for which no experimental data exist. These cross sections are from the full continuum distorted wave method (CDW). We first compute atomic cross sections in the independent electron model and then generate the corresponding molecular cross sections. The latter follow from the former within the independent atom model accompanied by the Bragg additivity rule. The investigated atomic targets are from the backbone of DNA and/or RNA molecules. These are atomic hydrogen, carbon, nitrogen and oxygen (H, C, N, O). Neon is also added to this sequence of targets as an isoelectronic atomic counterpart of water vapor, methane and ammonia molecules. The studied molecular targets are H2O (water vapor), CO (carbon-monoxide), CO2 (carbon-dioxide), CH4 (methane), C2H4 (ethylene), C2H6 (ethane), C4H10 (butane) as well as the DNA/RNA nucleobases C4H4N2O2 (uracil), C5H5N5 (adenine), C5H5N5O (guanine), C5H6N2O2 (thymine) and C4H5N3O (cytosine). The obtained total cross sections for any electronic target shell are compared with the available experimental data and overall favorable agreement is recorded at intermediate and high impact energies, which is the validity domain of the CDW method.


System design of a clinical facility for diagnostic ultrasound.
This two-part report sets out the fundamental considerations that are necessary for the successful development and functioning of a clinical diagnostic ultrasound facility. Part 1, "Establishing a Clinical Diagnostic Ultrasound Facility," deals with the myriad details that must be considered when establishing such a facility. Part 2, "Managing a Clinical Diagnostic Ultrasound Facility," is concerned with the functioning of the facility once it is established.


Risk profile of individuals who provide assistance with illicit drug injections.
Assisted injection is a common practice among injection drug users (IDU) that carries significant risk for health-related harm. However, little is known about the individuals who provide assistance with injections. We evaluated factors associated with providing help injecting among participants enrolled in the Vancouver Injection Drug User Study (VIDUS) using univariate and logistic regression analyses. We also examined self-reported relationships between the provider and the receiver of assisted injection, if compensation was provided for assistance, and what type of compensation was given. Of the 704 IDU eligible for this analysis, 193 (27.4%) had provided help injecting during the last 6 months. Variables independently associated with providing help injecting included: lending one's own syringe (adjusted odds ratio [AOR] = 3.99, p = 0.004); frequent heroin injection (AOR = 3.75, p < 0.001); unstable housing (AOR = 2.15, p < 0.001); binge drug use (AOR = 2.01, p = 0.012); frequent cocaine injection (AOR = 1.95, p = 0.002); and frequent use of crack cocaine (AOR = 1.85, p = 0.002). Help was most often provided to a casual (47.2%) or a close friend (41.5%). Of the 96 (49.7%) individuals who received compensation for providing help, the most common forms of compensation were drugs (89.6%) and money (45.8%). Providing help injecting was common among IDU in this cohort and was associated with various high-risk behaviours, including elevated levels of syringe lending. These findings indicate the need for interventions that offset the risks associated with this dangerous practice.


A method for harvesting viable cells from wound dressings.
Wound fluid has been well studied for exploring protein biomarkers contained in it. However, cells in wound fluid have not received much attention due to the difficulty in their collection. Our study aimed to establish a method for collecting viable cells from discarded wound dressings. A protocol was designed to wash out nonadherent cells and detach adherent cells from silicone-faced foam wound dressings using trypsin-EDTA. The optimal concentration and incubation time of trypsin-EDTA for collecting equivalent proportions of different cell types to the original cell population were determined in vitro. Cell composition and gene expression changes in monocytes, lymphocytes, neutrophils, fibroblasts and keratinocytes were confirmed using immunocytochemistry and RNA-sequencing ex vivo. Full-thickness wounds were created on 9-week-old male C57BL/6J mice. Wound fluid was collected, and half of it was applied to the wound dressings. The original cell population in the wound fluid and the cell population collected from wound dressings were compared. In the in vitro study, 0.25% trypsin-EDTA and 2.5-min incubation time were considered optimal for collecting adherent cells from wound dressings. In the ex vivo study, among all cell types, only CD3+ lymphocytes showed a significantly higher cell proportion in the collected group. The relative gene expression of the five selected cells showed no significant changes (p-value >0.05, |log2 fold change| < 1.5, differential gene expression analysis). Viable nonadherent and adherent cells were collected from wound dressings without altering gene expression and could be used in future studies for cellular analysis of wound fluid.


Alcohol prevention at sporting events: study protocol for a quasi-experimental control group study.
Alcohol intoxication and overserving of alcohol at sporting events are of great concern, given the relationships between alcohol consumption, public disturbances, and violence. During recent years this matter has been on the agenda for Swedish policymakers, authorities and key stakeholders, with demands that actions be taken. There is promising potential for utilizing an environmental approach to alcohol prevention as a strategy to reduce the level of alcohol intoxication among spectators at sporting events. Examples of prevention strategies may be community mobilization, Responsible Beverage Service training, policy work, and improved controls and sanctions. This paper describes the design of a quasi-experimental control group study to examine the effects of a multi-component community-based alcohol intervention at matches in the Swedish Premier Football League. A baseline assessment was conducted during 2015 and at least two follow-up assessments will be conducted in 2016 and 2017. The two largest cities in Sweden are included in the study, with Stockholm as the intervention area and Gothenburg as the control area. The setting is Licensed Premises (LP) inside and outside Swedish football arenas, in addition to arena entrances. Spectators are randomly selected and invited to participate in the study by providing a breath alcohol sample as a proxy for Blood Alcohol Concentration (BAC). Actors are hired and trained by an expert panel to act out a standardized scene of severe pseudo-intoxication. Four types of cross-sectional data are generated: (i) BAC levels among ≥ 4 200 spectators, frequency of alcohol service to pseudo-intoxicated patrons attempting to purchase alcohol at LP (ii) outside the arenas (≥200 attempts) and (iii) inside the arenas (≥ 200 attempts), and (iv) frequency of security staff interventions towards pseudo-intoxicated patrons attempting to enter the arenas (≥ 200 attempts). There is an urgent need nationally and internationally to reduce alcohol-related problems at sporting events, and it is essential to test prevention strategies to reduce intoxication levels among spectators. This project makes an important contribution not only to the research community, but also to enabling public health officials, decision-makers, authorities, the general public, and the sports community, to implement appropriate evidence-based strategies.


Brain natriuretic peptide increases in septic patients without severe sepsis or shock.
B-type natriuretic peptide (BNP) production increases in critically ill septic patients. We assessed the hypothesis that BNP is elevated in patients with community-acquired infections without severe sepsis or septic shock. We studied 54 patients [20 males, median age 39 (interquartile range 23, 71)] without heart disease, persistent arrhythmias, or renal failure. BNP was measured in all patients at hospital admission and at pre-discharge and in a control group of 52 individuals. Myoglobin levels were also measured in septic patients. The infection was microbial in 40 patients, viral in 11, and of undefined etiology in 3. A systemic inflammatory response was evident in 38 patients on the initial evaluation. BNP on admission was higher in patients than in controls [25 (10, 82) pg/ml vs. 13 (5, 30) pg/ml, p=0.01] and it decreased to 16 (5, 47) pg/ml pre-discharge (p=0.0002). Multiple logistic regression identified the presence of microbial infection as the only independent predictor of an elevated BNP value on admission [adjusted odds ratio 9.8 (1.02-93.8), p=0.04]. In patients with microbial infection, location of infection in the lower respiratory tract and the presence of diabetes mellitus were independent predictors of the magnitude of BNP increase. Myoglobin was also increased on hospital admission 80 (37, 231) ng/ml and decreased pre-discharge to 59 (38, 94) ng/ml, p=0.004. Myoglobin level changes from admission to discharge were more prominent with increasing age and in females. BNP levels are elevated in the acute phase of community-acquired microbial infections without severe sepsis or septic shock.


Inhibition of adenosylmethionine decarboxylase and perturbation of polyamine metabolism by 3-deaza-(+/-)aristeromycin.
3-Deaza-(+/-)aristeromycin, previously known mainly as a potent inhibitor of adenosylhomocysteine hydrolase, can also inhibit the activity of adenosylmethionine decarboxylase. The release of [14C]CO2 from HeLa cells labeled with [carboxyl-14C]methionine was inhibited by more than 70% after 4 hours in the presence of 4 microM 3-deaza-(+/-)aristeromycin. Concomitant with this inhibition, there was a significant increase in the amount of putrescine in the HeLa cells. Adenosylmethionine decarboxylase isolated from HeLa cells could also be inhibited by 3-deaza-(+/-)aristeromycin and 3-deazaadenosine, 3-deazaadenosylhomocysteine, and 3-deaza-(+/-)aristeromycinylhomocysteine.