Predictors of compassion satisfaction among healthcare professionals working in intensive care units: A cross-sectional study.
To determine the prevalence of compassion satisfaction, related factors, and predictors among healthcare professionals in Thai intensive care units. A cross-sectional study was conducted in 12 intensive care units at a university hospital in Thailand from August to November 2022. All nurses and doctors were invited to complete an anonymous online survey which included: the Professional Quality of Life Scale version 5, Connor-Davidson Resilience Scale, Passion Scale, Flourishing Scale, and Acceptance and Action Questionnaire. Descriptive statistics, Pearson's correlation coefficients, and hierarchical multiple regressions were used for data analysis in SPSS 28.0. A total of 178 nurses and doctors participated (92.13% nurses, 89.89% female, mean 32.10 years). Average compassion satisfaction (assessed using the Professional Quality of Life Scale) was moderate, with a mean score of 37.94 (SD = 5.58). The final regression model predicting compassion satisfaction was significant and explained 65% of the variance in compassion satisfaction, F (11, 154) = 26.00, p < 0.001. Four out of 11 predictor variables made unique statistically significant contributions to the final model: resilience (β = 0.48, p < 0.001), harmonious passion (β = 0.24, p < 0.001), being a nurse (not a doctor; β = 0.17, p < 0.05), and holding a postgraduate qualification (β = 0.10, p < 0.05). Most healthcare professionals in critical care units have a moderate level of compassion satisfaction, which is correlated with resilience, flourishing, and harmonious passion. Resilience and harmonious passion predict compassion satisfaction. These factors are modifiable through intervention. Assessment of staff psychological well-being can identify those at risk for stress and impaired professional quality of life. Resilience and harmonious passion predict compassion satisfaction and can be modified through psychological interventions to promote psychological well-being and professional quality of life in healthcare workers in intensive care units.


[A dreamed cooperation: Stakeholder query in Flemish Limburg concerning cooperation in the field of mental healthcare for older people].
This study is an extensive stakeholder query on cooperation in the field of mental healthcare for older people. Cooperation is a key theme in the current policy on mental healthcare in Flanders which is an application of the socialisation of care. The consultative platform SPIL recruited representatives of the primary healthcare through local consultative platforms (POP) and other relevant actors. This qualitative study used the appreciative inquiry in focus groups. There were 12 focus groups with a total of 110 participants, asked to dream of an ideal cooperation. Results show a great willingness to work together effectively with a central role for the patient. Participants seek knowledge, expertise and practical support from each other. They request a consult feature to know where to turn to. The main premise to cooperation is knowing each other, for which time and space is needed. A joint patient record is another request. No great new projects are requested. Focus must go to further elaboration of working together.


Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates.
An approach to use multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors (GPCRs) was recently introduced. A known adenosine receptor (AR) agonist was conjugated to polyamidoamine (PAMAM) dendrimer carriers for delivery of the intact covalent conjugate to on the cell surface. Depending on the linking moiety, multivalent conjugates of the N6-chain elongated functionalized congener ADAC (N6-[4-[[[4-[[[(2-aminoethyl)amino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl]-adenosine) achieved unanticipated high selectivity in binding to the cytoprotective human A3 AR, a class A GPCR. The key to this selectivity of > 100-fold in both radioreceptor binding (Ki app = 2.4 nM) and functional assays (EC50 = 1.6 nM in inhibition of adenylate cyclase) was maintaining a free amino group (secondary) in an amide-linked chain. Attachment of neutral amide-linked chains or thiourea-containing chains preserved the moderate affinity and efficacy at the A1 AR subtype, but there was no selectivity for the A3 AR. Since residual amino groups on dendrimers are associated with cytotoxicity, the unreacted terminal positions of this A3 AR-selective G2.5 dendrimer were present as carboxylate groups, which had the further benefit of increasing water-solubility. The A3 AR selective G2.5 dendrimer was also visualized binding the membrane of cells expressing the A3 receptor but did not bind cells that did not express the receptor. This is the first example showing that it is feasible to modulate and even enhance the pharmacological profile of a ligand of a GPCR based on conjugation to a nanocarrier and the precise structure of the linking group, which was designed to interact with distal extracellular regions of the 7 transmembrane-spanning receptor. This ligand tool can now be used in pharmacological models of tissue rescue from ischemia and to probe the existence of A3 AR dimers.


Ruptured vascular malformation masquerading as battered/shaken baby syndrome: a nearly tragic mistake.
Battered/shaken baby syndrome is a clinical and pathologic diagnosis based on clinical examination, central nervous system dysfunction, and intracranial, optic nerve sheath, and retinal hemorrhages in infants under the age of three years. This report describes a case in which the battered/shaken baby syndrome was suspected because of an unusual parental reaction to an acute, mortal illness in their seven-week-old baby, as well as an acute intracranial hemorrhage coupled with the discovery of optic nerve sheath hemorrhages at necropsy. Thorough microscopic study, however, uncovered an unusual subarachnoid vascular malformation, the rupture of which led to the death of the infant. This case underscores the importance of complete postmortem examinations in cases of suspected child abuse, and teaches caution in jumping to hasty conclusions.


Whipple's disease.
Whipple's disease is a chronic, multisystem disease that is caused by Tropheryma whippelii infection. More information is now known about this unusual infectious process, which was once considered uniformly fatal. Immunologic, diagnostic, and therapeutic advancements are reviewed in this article. Hopefully, future advances in the basic and clinical sciences will lead to a more rapid diagnosis, more complete understanding of the effects of infection, improved therapy, and better clinical outcome.


MIS-C is a Clinically Different Entity from Acute COVID-19 in Adults.
Mehra B, Aggarwal V, Kumar P, Gupta D, Kundal M, Kumar A, et al. MIS-C is a Clinically Different Entity from Acute COVID-19 in Adults. Indian J Crit Care Med 2021;25(8):954-955.


New bisfuran derivative from sarsasapogenin. An X-ray and NMR analysis.
The new bisfuran derivative, (22S,23S)-22,23-dihydroxy-23,26-epoxyfurostane, was obtained from the known oxidation of sarsasapogenin acetate with NaNO2/BF3 in 5% aqueous acetic acid. The structure of was established using one and two-dimensional 1H, 13C experiments (DEPT, COSY, HETCOR and HMBC) and the configurations at the newly formed stereogenic centers were established as 22S,23S by an X-ray diffraction analysis. Addition of TiCl4 to bisfuran 5 confirmed that this compound is an intermediate in the rearrangement to 22-oxo-23-spiroketals since it was transformed quantitatively into the latter product. The 23-nitroimino intermediate 2 was isolated from the same reaction and its structure established also by an X-ray diffraction analysis; this compound was further transformed into the 23-nitramine 7 which could find application in functionalization of position 24.


Function of chloroplast RNA-binding proteins.
Chloroplasts are eukaryotic organelles which represent evolutionary chimera with proteins that have been derived from either a prokaryotic endosymbiont or a eukaryotic host. Chloroplast gene expression starts with transcription of RNA and is followed by multiple post-transcriptional processes which are mediated mainly by an as yet unknown number of RNA-binding proteins. Here, we review the literature to date on the structure and function of these chloroplast RNA-binding proteins. For example, the functional protein domains involved in RNA binding, such as the RNA-recognition motifs, the chloroplast RNA-splicing and ribosome maturation domains, and the pentatricopeptide-repeat motifs, are summarized. We also describe biochemical and forward genetic approaches that led to the identification of proteins modifying RNA stability or carrying out RNA splicing or editing. Such data will greatly contribute to a better understanding of the biogenesis of a unique organelle found in all photosynthetic organisms.


Low concentration of 2,4,6-tribromophenol (TBP) represents a risk to South American silver catfish Ramdia quelen (Quoy and Gaimard, 1824) population.
The 2,4,6-tribromophenol (TBP) is an environmental persistent pollutant widely used as flame retardant, antimicrobial and insecticide agent in wood preservation and plastic production. Currently, TBP is found in environmental compartments such as soil, freshwater, groundwater, sewage sludge and domestic dust, but the effects to biota and the risk of exposure to aquatic vertebrates are still scarce. In the present study, Rhamdia quelen fish embryos (8 h post-fertilization - hpf) were exposed to 0.3 and 3.0 μg L-1 of TBP until 96 hpf. Biochemical biomarkers, hatching, survival and larvae/embryo malformations were evaluated after exposure. Additionally, a mathematical model was proposed to evaluate the effects along further generations. The results showed that TBP decreased the survival level but did not cause significant difference in the hatching rates. After 72 and 96 hpf, individuals from the highest tested concentration group showed more severe malformations than individuals from control and the lower concentrations groups. The deformities were concentrated on the embryos facial region where the sensorial structures related to fish behavior are present. The biochemical biomarkers revealed both oxidative stress and neurotoxicity signs after exposure to the contaminant, while the application of the mathematical model showed a decrease of population in both tested TBP concentrations. In conclusion, the current results demonstrated that TBP is toxic to R. quelen embryos and represents a risk to population after early life stage exposure.


Expression profile of small RNAs in Acacia mangium secondary xylem tissue with contrasting lignin content - potential regulatory sequences in monolignol biosynthetic pathway.
Lignin, after cellulose, is the second most abundant biopolymer accounting for approximately 15-35% of the dry weight of wood. As an important component during wood formation, lignin is indispensable for plant structure and defense. However, it is an undesirable component in the pulp and paper industry. Removal of lignin from cellulose is costly and environmentally hazardous process. Tremendous efforts have been devoted to understand the role of enzymes and genes in controlling the amount and composition of lignin to be deposited in the cell wall. However, studies on the impact of downregulation and overexpression of monolignol biosynthesis genes in model species on lignin content, plant fitness and viability have been inconsistent. Recently, non-coding RNAs have been discovered to play an important role in regulating the entire monolignol biosynthesis pathway. As small RNAs have critical functions in various biological process during wood formation, small RNA profiling is an important tool for the identification of complete set of differentially expressed small RNAs between low lignin and high lignin secondary xylem. In line with this, we have generated two small RNAs libraries from samples with contrasting lignin content using Illumina GAII sequencer. About 10 million sequence reads were obtained in secondary xylem of Am48 with high lignin content (41%) and a corresponding 14 million sequence reads were obtained in secondary xylem of Am54 with low lignin content (21%). Our results suggested that A. mangium small RNAs are composed of a set of 12 highly conserved miRNAs families found in plant miRNAs database, 82 novel miRNAs and a large proportion of non-conserved small RNAs with low expression levels. The predicted target genes of those differentially expressed conserved and non-conserved miRNAs include transcription factors associated with regulation of the lignin biosynthetic pathway genes. Some of these small RNAs play an important role in epigenetic silencing. Differential expression of the small RNAs between secondary xylem tissues with contrasting lignin content suggests that a cascade of miRNAs play an interconnected role in regulating the lignin biosynthetic pathway in Acacia species. Our study critically demonstrated the roles of small RNAs during secondary wall formation. Comparison of the expression pattern of small RNAs between secondary xylem tissues with contrasting lignin content strongly indicated that small RNAs play a key regulatory role during lignin biosynthesis. Our analyses suggest an evolutionary mechanism for miRNA targets on the basis of the length of their 5' and 3' UTRs and their cellular roles. The results obtained can be used to better understand the roles of small RNAs during lignin biosynthesis and for the development of gene constructs for silencing of specific genes involved in monolignol biosynthesis with minimal effect on plant fitness and viability. For the first time, small RNAs were proven to play an important regulatory role during lignin biosynthesis in A. mangium.


Glucose control in sepsis.
Hyperglycemia is common during the course of critical illness and is associated with adverse clinical outcomes. Randomized controlled trials and large observational trials of insulin therapy titrated to achieve glucose values approximating the normal range (80 to 110 mg/dL) demonstrate improved morbidity and mortality in heterogeneous populations and have led to recommendations for improved glucose control. Patients who have septic shock, however, appear to be at higher risk for hypoglycemia, and a recent randomized trial focusing exclusively on patients who had severe sepsis did not show benefit. The recent Surviving Sepsis consensus statement recommends insulin therapy using validated protocols to lower glucose (less than 150 mg/dL) pending the results of adequately powered trials to determine if normalization (less than 110 mg/dL) of glucose is needed to optimize outcomes in patients who have severe sepsis.


A feasibility cluster randomised controlled trial of a preschool obesity prevention intervention: ToyBox-Scotland.
High levels of childhood obesity have been observed globally over the last three decades. Preschools are promising settings to implement obesity prevention interventions in the early years. The aim of this study was to test the feasibility of a cluster randomised controlled trial of the ToyBox-Scotland preschool obesity prevention intervention. Six preschools in predominantly deprived areas of Glasgow, UK, were randomised to either the ToyBox intervention (n = 3) or usual curriculum control group (n = 3). The intervention ran for 18 weeks from March-June 2018, and consisted of practitioner-led physical activity and sedentary behaviour sessions in preschools, with an additional interactive home component. Primary outcome measures were intervention fidelity, recruitment rates, attrition rates, and compliance with trial procedures. Secondary outcomes were body mass index (BMI) z-score, bioelectrical impedance analysis (BIA), objectively measured physical activity and sedentary time via activPAL accelerometer, and parent-reported home eating, snacking, and water consumption. The preschool component of the intervention was implemented with high fidelity (64%), while the home component was implemented with low fidelity (41%). A cluster-level recruitment rate of 10% was achieved, and the individual-level recruitment rate was 18% (42/233 children, mean age 4.4 years; 17 girls). The attrition rate was 14%, and compliance rates varied considerably by the outcome. Compliance was highest for BMI (86%), while 19% of the sample returned valid accelerometer data for both baseline and follow-up and the parental questionnaire response rate was 23%. Both intervention and control groups showed small increases in BMI z-scores at follow-up of 0.02 and 0.06, respectively. Both groups had small decreases in physical activity and increases in sedentary time at follow-up. Before progression to an effectiveness trial, additional procedures should be considered to improve recruitment rates, compliance with outcome measures, and implementation of the home-based component of the ToyBox-Scotland intervention. ISRCTN12831555.


Vertical Farming: Moving from Genetic to Environmental Modification.
Vertical farming (VF) is a novel plant production system that allows local production of high-quality fruits and vegetables for rapidly growing cities. VF offers a myriad of opportunities to move from genetic to environmental modification and to produce crops of guaranteed quality and quantity independent of weather, soil conditions, or climate change.


Enzyme-antibody conjugation by a heterobifunctional reagent and its application in enzyme-linked immunosorbent assay (ELISA) for the detection of hepatitis B surface antigen.
The heterobifunctional reagent 3-(2-pyridyl-dithio)propionate (SPDP) was used to prepare defined conjugates composed of horseradish peroxidase (HRP) and goat anti-HBs IgG. The modification of HRP and IgG with SPDP was dependent on both the SPDP: protein molar ratio and the pH of the buffer. Conjugates were separated by a single affinity chromatographic step using concanavalin A-Sepharose 4B equilibrated with 0.1 M Tris-HCl buffer, pH 7.4, containing 0.5 M KCl and 1 mM EDTA. The conjugate was eluted with 10 or 100 mM alpha-methyl-D-mannoside and appropriate pools were made reflecting various HRP/IgG molar ratios. Each pool was examined for performance in an enzyme-linked immunosorbent assay for HBsAg. Conjugate composed of an HRP/IgG molar ratio of 2.5-4 yielded the greatest sensitivity.


GABA inhibition of central angiotensin II and hypertonic CSF pressor responses.
Angiotensin II (AII), hypertonic cerebrospinal fluid (CSF) and serotonin produced an increase in arterial pressure when administered intraventricularly (IVT) in conscious rats. Injection of 25 and 100 micrograms (IVT) of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), while producing slight hypotension, reduced the pressor effect of centrally administered AII and hypertonic CSF, but not serotonin. IVT-administered muscimol, a potent GABA agonist, also attenuated the pressor effect of IVT AII and hypertonic CSF. Thus, in addition to the profound depressor effect of large doses of centrally administered GABA, very low doses (25-100 micrograms, IVT) of this amino acid can alter the pressor responses caused by IVT injection of AII and hypertonic CSF.


Organic-inorganic hybrid [NH3(CH2)6NH3]ZnBr4 crystal: structural characterization, phase transitions, thermal properties, and structural dynamics.
Organic-inorganic hybrid [NH3(CH2)6NH3]ZnBr4 crystals were prepared by slow evaporation; the crystals had a monoclinic structure with space group P21/c and lattice constants a = 7.7833 Å, b = 14.5312 Å, c = 13.2396 Å, β = 90.8650°, and Z = 4. They underwent two phase transitions, at 370 K (T C1) and 430 K (T C2), as confirmed by powder X-ray diffraction patterns at various temperatures; the crystals were stable up to 600 K. The nuclear magnetic resonance spectra, obtained using the magic-angle spinning method, demonstrated changes in the 1H and 13C chemical shifts were observed near T C1, indicating changing structural environments around 1H and 13C. The spin-lattice relaxation time, T 1ρ, increased rapidly near T C1 suggesting very large energy transfer, as indicated by a large thermal displacement around the 13C atoms of the cation. However, the environments of 1H, 14N, and C1 located close to NH3 in the [NH3(CH2)6NH3] cation did not influence it significantly, indicating a minor change in the N-H⋯Br hydrogen bond with the coordination geometry of the ZnBr4 anion. We believe that the information on the physiochemical properties and thermal stability of [NH3(CH2)6NH3]ZnBr4, as discussed in this study, would be key to exploring its application in stable, environment friendly solar cells.


Classification based on event in survival machine learning analysis of cardiovascular disease cohort.
The aim of this study is to assess the effectiveness of supervised learning classification models in predicting patient outcomes in a survival analysis problem involving cardiovascular patients with a significant cured fraction. The sample comprised 919 patients (365 females and 554 males) who were referred to Sulaymaniyah Cardiac Hospital and followed up for a maximum of 650 days between 2021 and 2023. During the research period, 162 patients (17.6%) died, and the cure fraction in this cohort was confirmed using the Mahler and Zhu test (P < 0.01). To determine the best patient status prediction procedure, several machine learning classifications were applied. The patients were classified into alive and dead using various machine learning algorithms, with almost similar results based on several indicators. However, random forest was identified as the best method in most indicators, with an Area under ROC of 0.934. The only weakness of this method was its relatively poor performance in correctly diagnosing deceased patients, whereas SVM with FP Rate of 0.263 performed better in this regard. Logistic and simple regression also showed better performance than other methods, with an Area under ROC of 0.911 and 0.909 respectively.


Effects of population structure on pollen flow, clonality rates and reproductive success in fragmented Serapias lingua populations.
Fragmentation of habitats by roads, railroads, fields, buildings and other human activities can affect population size, pollination success, sexual and asexual reproduction specially in plants showing pollinator limitation, such as Mediterranean orchids. In this study, we assessed pollen flow, selfing rates, vegetative reproduction and female reproductive success and their correlations with habitat characters in nine fragmented subpopulations of Serapias lingua. To improve understanding of population structure effects on plant biology, we examined genetic differentiation among populations, pollen flow, selfing rates and clonal reproduction using nuclear microsatellite markers. Smaller populations showed a significant heterozygote deficit occurred at all five nuclear microsatellite loci, the coefficient of genetic differentiation among populations was 0.053 and pairwise FST was significantly correlated with the geographical distance between populations. Paternity analysis of seeds showed that most pollen flow occurred within a population and there was a positive correlation between percentage of received pollen and distance between populations. The fruit production rate varied between 5.10 % and 20.30 % and increased with increasing population size, while the percentage of viable seeds (78-85 %) did not differ significantly among populations. The extent of clonality together with the clonal and sexual reproductive strategies varied greatly among the nine populations and correlated with the habitats where they occur. The small, isolated populations tended to have high clonal diversity and low fruit production, whereas the large populations with little disturbance were prone to have reductions in clonal growth and increased sexual reproduction. We found that clonality offers an advantage in small and isolated populations of S. lingua, where clones may have a greater ability to persist than sexually reproducing individuals.


Accuracy of impression materials for complete-arch fixed partial dentures.
The accuracy of 12 impression materials of six different types were studied by using complete-arch FPD impressions. Sixty impressions were made of a Columbia dentoform maxillary model with complete cast crown abutment preparations on the canines and the second molars. A one-piece casting was constructed by connecting the four individual castings made for the four abutment teeth. The master prosthesis was seated on the stone casts produced from the impressions. The marginal adaptation on the four abutments was then evaluated with a travelling microscope. The individual marginal adaptation of the four castings on the abutments was also examined after sectioning the four joints. The following conclusions were drawn. 1. The polyethers produced the most accurate complete-arch replicas. The second most accurate were the vinyl polysiloxanes, followed by the polysulfides and the irreversible-reversible hydrocolloids. The least accurate were the reversible hydrocolloids and the irreversible hydrocolloids. 2. The polyether impression materials exhibited the most consistent accuracy for a master cast to fabricate a complete-arch FPD.


Toxic nephropathies.
The general topic of kidney damage produced by drugs and toxins is introduced, emphasizing its clinical importance in critically ill patients. Specific toxins are then examined in detail with respect to the mechanisms of toxicity, clinical features, and management.


Monte Carlo dosimetry of a new (90)Y brachytherapy source.
In this study, we attempted to obtain full dosimetric data for a new (90)Y brachytherapy source developed by the College of Chemistry (Sichuan University) for use in high-dose-rate after-loading systems. The dosimetric data for this new source were used as required by the dose calculation formalisms proposed by the AAPM Task Group 60 and Task Group 149. The active core length of the new (90)Y source was increased to 4.7 mm compared to the value of 2.5 mm for the old (90)Sr/(90)Y source. The Monte Carlo simulation toolkit Geant4 was used to calculate these parameters. The source was located in a 30-cm-radius theoretical sphere water phantom. The dosimetric data included the reference absorbed dose rate, the radial dose function in the range of 1.0 to 8.0 mm in the longitudinal axis, and the anisotropy function with a θ in the range of 0° to 90° at 5° intervals and an r in the range of 1.0 to 8.0 mm in 0.2-mm intervals. The reference absorbed dose rate for the new (90)Y source was determined to be equal to 1.6608 ± 0.0008 cGy s(-1) mCi(-1), compared to the values of 0.9063 ± 0.0005 cGy s(-1) mCi(-1) that were calculated for the old (90)Sr/(90)Y source. A polynomial function was also obtained for the radial dose function by curve fitting. Dosimetric data are provided for the new (90)Y brachytherapy source. These data are meant to be used commercially in after-loading system.


Improvement in the medial meniscus posterior shift following anterior cruciate ligament reconstruction.
Anterior cruciate ligament (ACL) reconstruction can reduce the risk of developing osteoarthritic knees. The goals of ACL reconstruction are to restore knee stability and reduce post-traumatic meniscal tears and cartilage degradation. A chronic ACL insufficiency frequently results in medial meniscus (MM) injury at the posterior segment. How ACL reconstruction can reduce the deformation of the MM posterior segment remains unclear. In this study, we evaluated the form of the MM posterior segment and anterior tibial translation before and after ACL reconstruction using open magnetic resonance imaging (MRI). Seventeen patients who underwent ACL reconstructions without MM injuries were included in this study. MM deformation was evaluated using open MRI before surgery and 3 months after surgery. We measured medial meniscal length (MML), medial meniscal height (MMH), medial meniscal posterior body width (MPBW), MM-femoral condyle contact width (M-FCW) and posterior tibiofemoral distance (PTFD) at knee flexion angles of 10° and 90°. There were no significant pre- and postoperative differences during a flexion angle of 10°. At a flexion angle of 90°, MML decreased from 43.7 ± 4.5 to 41.4 ± 4.5 mm (P < 0.001), MMH from 7.5 ± 1.4 to 6.9 ± 1.4 mm (P = 0.006), MPBW from 13.1 ± 2.0 to 12.2 ± 1.9 mm (P < 0.001) and M-FCW from 10.0 ± 1.5 to 8.5 ± 1.5 mm (P < 0.001) after ACL reconstruction. The PTFD increased from 2.1 ± 2.8 to 2.7 ± 2.4 mm after ACL reconstruction (P = 0.015). ACL reconstruction affects the contact pattern between the MM posterior segment and medial femoral condyle and can reduce the deformation of the MM posterior segment in the knee-flexed position by reducing abnormal anterior tibial translation. It possibly prevents secondary injury to the MM posterior segment and cartilage that progresses to knee osteoarthritis. IV.


The C-terminal domain of MinC, a cell division regulation protein, is sufficient to form a copolymer with MinD.
Assembly of cell division protein FtsZ into the Z-ring at the division site is a key step in bacterial cell division. The Min proteins can restrict the Z-ring to the middle of the cell. MinC is the main protein that obstructs Z-ring formation by inhibiting FtsZ assembly. Its N-terminal domain (MinCN ) regulates the localization of the Z-ring by inhibiting FtsZ polymerization, while its C-terminal domain (MinCC ) binds to MinD as well as to FtsZ. Previous studies have shown that MinC and MinD form copolymers in vitro. This copolymer may greatly enhance the binding of MinC to FtsZ, and/or prevent FtsZ filaments from diffusing to the ends of the cell. Here, we investigated the assembly properties of MinCC -MinD of Pseudomonas aeruginosa. We found that MinCC is sufficient to form the copolymers. Although MinCC -MinD assembles into larger bundles, most likely because MinCC is spatially more readily bound to MinD, its copolymerization has similar dynamic properties: the concentration of MinD dominates their copolymerization. The critical concentration of MinD is around 3 μm and when MinD concentration is high enough, a low concentration MinCC could still be copolymerized. We also found that MinCC -MinD can still rapidly bind to FtsZ protofilaments, providing direct evidence that MinCC also interacts directly with FtsZ. However, although the presence of minCC can slightly improve the division defect of minC-knockout strains and shorten the cell length from an average of 12.2 ± 6.7 to 6.6 ± 3.6 μm, it is still insufficient for the normal growth and division of bacteria.


Interfering with airway nerves in cough associated with asthma.
Cough is a troublesome and often refractory symptom of asthma, which is associated with poor control of disease. The pathogenesis of asthmatic cough has mainly been attributed to bronchoconstriction, but recent evidence indicate that cough reflex hypersensitivity or neuronal dysfunction is a feature of asthma, even in those with mild stable disease. This is likely resistant to the mainstay treatment ICS/LABA which inhibits classic asthmatic response. Such refractory cough might manifest more predominantly in the day-time rather than night-time. Treatment options of such refractory cough or cough reflex hypersensitivity in asthma targeting the nerves (LTRAs, tiotropium, and potentially bronchial thermoplasty) are discussed.


Near Field Communication-based telemonitoring with integrated ECG recordings.
Telemonitoring of vital signs is an established option in treatment of patients with chronic heart failure (CHF). In order to allow for early detection of atrial fibrillation (AF) which is highly prevalent in the CHF population telemonitoring programs should include electrocardiogram (ECG) signals. It was therefore the aim to extend our current home monitoring system based on mobile phones and Near Field Communication technology (NFC) to enable patients acquiring their ECG signals autonomously in an easy-to-use way. We prototypically developed a sensing device for the concurrent acquisition of blood pressure and ECG signals. The design of the device equipped with NFC technology and Bluetooth allowed for intuitive interaction with a mobile phone based patient terminal. This ECG monitoring system was evaluated in the course of a clinical pilot trial to assess the system's technical feasibility, usability and patient's adherence to twice daily usage. 21 patients (4f, 54 ± 14 years) suffering from CHF were included in the study and were asked to transmit two ECG recordings per day via the telemonitoring system autonomously over a monitoring period of seven days. One patient dropped out from the study. 211 data sets were transmitted over a cumulative monitoring period of 140 days (overall adherence rate 82.2%). 55% and 8% of the transmitted ECG signals were sufficient for ventricular and atrial rhythm assessment, respectively. Although ECG signal quality has to be improved for better AF detection the developed communication design of joining Bluetooth and NFC technology in our telemonitoring system allows for ambulatory ECG acquisition with high adherence rates and system usability in heart failure patients.


Enhancement of soluble expression of codon-optimized Thermomicrobium roseum sarcosine oxidase in Escherichia coli via chaperone co-expression.
The codon-optimized sarcosine oxidase from Thermomicrobium roseum (TrSOX) was successfully expressed in Escherichia coli and its soluble expression was significantly enhanced via the co-expression of chaperones. With the assistance of whole-genome analysis of T. roseum DSM 5159, the sox gene was predicated and its sequence was optimized based on the codon bias of E. coli. The TrSOX gene was successfully constructed in the pET28a plasmid. After induction with IPTG for 8h, SDS-PAGE analysis of crude enzyme solutions showed a significant 43 kDa protein band, indicating SOX was successfully expressed in E. coli. However, the dark band corresponding to the intracellular insoluble fraction indicated that most of TrSOX enzyme existed in the inactive form in "inclusion bodies" owing to the "hot spots" of TrSOX. Furthermore, the co-expression of five different combinations of chaperones indicated that the soluble expression of TrSOX was greatly improved by the co-expression of molecular chaperones GroES-GroEL and DnaK-DnaJ-GrpE-GroES-GroEL. Additionally, the analysis of intramolecular forces indicated that the hydrophobic amino acids, hydrogen bonds, and ionic bonds were favorable for enhancing the interaction and stability of TrSOX secondary structure. This study provides a novel strategy for enhancing the soluble expression of TrSOX in E. coli.


Differences in the health care needs and service utilization of women in nursing homes: comparison by race/ethnicity.
The purpose of this study is to describe health care needs and service utilization among institutionalized women of color. The sample was dichotomized by length of stay to determine how African American, Native American, Asian/Pacific Islander, and Hispanic/Latino women differed at two points in time. Data for this study came from the Current Resident Survey of the 1999 National Nursing Home Survey. The data were analyzed using GLM. The findings suggest that Native American women are the most impaired and Asian/Pacific Islander women are the least impaired. Additionally, very few women received mental health services despite their extensive need.


Photoinduced Ring-Opening and Phototoxicity of an Indolin-3-one Derivative.
The study of a fluorescent indolin-3-one derivative is reported that, as opposed to its previously described congeners, selectively undergoes photoactivated ring-opening in apolar solvents. The excited state involved in this photoisomerization was partially deactivated by the formation of singlet oxygen. Cell studies revealed lipid droplet accumulation and efficient light-induced cytotoxicity.


Pathological process has a crucial role in sentinel node biopsy for vulvar cancer.
To report the interim findings of an audit of the outcomes of sentinel node (SN) biopsy performed as a replacement for groin node dissection in women with early stage vulvar cancer in routine clinical practice in Australia and New Zealand. A prospective multi-center study in 8 participating centers. Eligible patients had squamous cell carcinomas clinically restricted to the vulva <4 cm in diameter. SN procedures and pathological assessment were to be performed in accordance with the methods published by the GROINSS-V collaboration [1]. 130 women with apparent early stage vulvar cancer were enrolled. Seventeen women subsequently did not meet the eligibility criteria and were excluded. SNs were identified in 111/113 of the remaining women. Twenty-two women had positive nodes. Sixteen of these women had at least 12 months follow up and 7 (44%) had recurrent disease. Eighty-nine women had only negative nodes. Seventy-four of these women had at least 12 months follow up and 6 (8%) had recurrent disease (including 2 [2.7%] with recurrence in the groin). On subsequent review of the two women with negative SNs who had groin recurrences, it was found that the recommended pathology protocol had not been followed. In both cases, SN metastases were identified following serial sectioning of the nodes. SN biopsy is feasible in routine clinical practice. However, undetected metastases in a removed SN may be associated with groin recurrence. To ensure patient safety, strict adherence to the pathology protocol is an essential component in the utilization of the sentinel lymph node technique in vulvar cancer.


A systems model of training for patients in phase 2 cardiac rehabilitation.
The aim of this study was to apply a systems model of training for athletes in patients with coronary artery disease (CAD) undergoing phase 2 cardiac rehabilitation. Data from six patients with CAD undergoing 20 conventional training sessions were used to test this model. The method required daily training quantification using heart rate, and regular assessment of real exercise tolerance using a constant-duration test. Convolution of training quantity with real exercise tolerance was provided for every patient model exercise tolerance, by minimizing the residual sum of squares. The results showed that application of the systems model of training to the six patients resulted in a strong fit between real and model exercise tolerances: r(2) = 0.77, 0.79, 0.83, 0.84, 0.85 and 0.92, respectively (P < 0.05). Moreover, the systems model admitted for all patients corresponded to one first-order transfer function, which was fitness. This result was in contrast with the systems models reported in athletes and in a patient with CAD undergoing phase 3 cardiac rehabilitation which were found to include two first-order transfer functions: fitness and fatigue, simultaneously. The systems model of training of patients with CAD undergoing phase 2 suggested two practical consequences: first, the improvement of exercise tolerance is directly related to training, and consequently second, patients who enter immediately phase 3 training may prevent a decrease in their exercise tolerance.


Distinct receptors for Leu- and Met-enkephalin on the metacerebral giant cell of Aplysia.
1. The effects of D-Ala2-Leu-enkephalin (DALEU), D-Ala2-Met-enkephalin (DAMET), and FMRFamide on the metacerebral cell (MCC) of Aplysia were determined in current- and voltage-clamp experiments. 2. Distinct receptors exist on this neuron for the three substances. 3. DALEU elicited a depolarizing response due to an inward current but not accompanied by a significant change in membrane conductance. 4. In contrast, DAMET elicited a hyperpolarizing response due to an outward current, also not associated with a significant change in membrane conductance. 5. Both the DALEU and the DAMET responses increased with hyperpolarization, decreased with depolarization, but did not reverse at potentials less than -30 mV. Neither response was sensitive to naloxone. 6. FMRFamide induced a voltage-dependent outward current that reversed at about -76 mV. This neuron was responsive to much lower concentrations of FMRFamide than either of the enkephalins, and the response to FMRFamide appears to be a conductance increase to K+. 7. These results suggest that the MCC neuron has distinct receptors for Leu- and Met-enkephalin that activate unusual responses of opposite polarity, as well as more usual inhibitory responses to FMRFamide.


Effect of season on the dynamics of cat sperm DNA fragmentation.
Feline species undergo reproductive seasonality; thus, sperm characteristics, such as DNA integrity, can be affected by the photoperiod. This study was conducted to determine the effect of seasonal changes on sperm quality and on the dynamics of sperm DNA fragmentation. Epididymal spermatozoa were collected from 36 tomcats subjected to bilateral orchiectomy during breeding (BS) and non-breeding (NBS) seasons. Sperm samples were obtained by cutting the cauda epididymis and assessed for sperm motility, concentration, acrosome integrity, plasma membrane integrity and sperm morphology. Sperm DNA fragmentation was evaluated by the sperm chromatin dispersion test after 0, 6, and 24 h of incubation at 37 °C. The total sperm motility and plasma membrane integrity values were greater during the BS, while the percentages of abnormal sperm and head defects were lesser (p < 0.05). No significant differences in DNA fragmentation were found between seasons after sperm collection. DNA damage was greater after 24 h of incubation at 37 °C in both seasons, although the percentage of spermatozoa with fragmented DNA was significantly lesser in the BS than in the NBS at 24 h (p < 0.05). The study suggests seasonal changes in some of the quality parameters of cat sperm. DNA fragmentation dynamics were affected by the time of incubation and reproductive season; therefore, this technique might be used as an additional tool to test the potential fertility of semen samples used in feline-assisted reproduction.


Radiomics analysis of bone marrow biopsy locations in [18F]FDG PET/CT images for measurable residual disease assessment in multiple myeloma.
The combination of visual assessment of whole body [18F]FDG PET images and evaluation of bone marrow samples by Multiparameter Flow Cytometry (MFC) or Next-Generation Sequencing (NGS) is currently the most common clinical practice for the detection of Measurable Residual Disease (MRD) in Multiple Myeloma (MM) patients. In this study, radiomic features extracted from the bone marrow biopsy locations are analyzed and compared to those extracted from the whole bone marrow in order to study the representativeness of these biopsy locations in the image-based MRD assessment. Whole body [18F]FDG PET of 39 patients with newly diagnosed MM were included in the database, and visually evaluated by experts in nuclear medicine. A methodology for the segmentation of biopsy sites from PET images, including sternum and posterior iliac crest, and their subsequent quantification is proposed. First, starting from the bone marrow segmentation, a segmentation of the biopsy sites is performed. Then, segmentations are quantified extracting SUV metrics and radiomic features from the [18F]FDG PET images and are evaluated by Mann-Whitney U-tests as valuable features differentiating PET+/PET- and MFC+ /MFC- groups. Moreover, correlation between whole bone marrow and biopsy sites is studied by Spearman ρ rank. Classification performance of the radiomics features is evaluated applying seven machine learning algorithms. Statistical analyses reveal that some images features are significant in PET+/PET- differentiation, such as SUVmax, Gray Level Non-Uniformity or Entropy, especially with a balanced database where 16 of the features show a p value < 0.001. Correlation analyses between whole bone marrow and biopsy sites results in significant and acceptable coefficients, with 11 of the variables reaching a correlation coefficient greater than 0.7, with a maximum of 0.853. Machine learning algorithms demonstrate high performances in PET+/PET- classification reaching a maximum AUC of 0.974, but not for MFC+/MFC- classification. The results demonstrate the representativeness of sample sites as well as the effectiveness of extracted features (SUV metrics and radiomic features) from the [18F]FDG PET images in MRD assessment in MM patients.


The serotype distribution of Streptococcus agalactiae (GBS) carriage isolates among pregnant women having risk factors for early-onset GBS disease: a comparative study with GBS causing invasive infections during the same period in Denmark.
We describe the serotype distribution of Streptococcus agalactiae (GBS) carriage isolates from women in labor and among GBS isolates causing invasive infections during the same period to see if the distribution of carriage serotypes reflects the GBS serotypes causing invasive diseases including early-onset disease (EOGBS). Data on invasive isolates from 2019 including serotype, erythromycin and clindamycin susceptibility was retrieved from the Danish national reference laboratory, Statens Serum Institut. Carriage isolates were collected from women with risk factors for EOGBS enrolled at delivery at the maternity ward at a Danish University Hospital, first half of 2019. Among carriage isolates, the dominant serotype was IX (21 %) followed by serotype III (19 %). The resistance to erythromycin and clindamycin was 21 and 26 %, respectively. Among invasive GBS isolates, no case of EOGBS with serotype IX was detected but the distribution of serotypes were otherwise similar to the GBS carrier strains. The corresponding resistance to erythromycin and clindamycin was 23 and 15 %, respectively. Penicillin resistance was not detected among carriage nor invasive isolates. The distribution of serotypes among carriage and invasive GBS reflects the assumption that EOGBS occur following transmission of GBS from mother to newborn, with the exception of serotype IX.


Radiological impact of the nuclear power plant accident on freshwater fish in Fukushima: An overview of monitoring results.
Radionuclide ((131)I, (134)Cs, and (137)Cs) concentrations of monitored freshwater fish species collected from different habitats (rivers, lakes, and culture ponds) in Fukushima Prefecture during March 2011-December 2014 (total 16 species, n = 2692) were analyzed to present a detailed description of radionuclide contamination after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, and to elucidate species-specific spatiotemporal declining trends of (137)Cs concentration for their respective habitats. Low concentrations of (131)I (≤24 Bq kg(-1)-wet) were detected from only 11 samples collected during March-June 2011, demonstrating that (131)I transferred to freshwater fish were not intense. In river and lake fishes, a more gradual decrease and higher radiocesium ((134)Cs, (137)Cs) concentrations were observed than in culture pond fishes, which strongly implied that radiocesium in freshwater fish species was mainly bioaccumulated through the food web in the wild. During 2011-2014, percentages above the Japanese regulatory limit of 100 Bq kg(-1)-wet for radiocesium in river and lake fish (14.0% and 39.6%, respectively) were higher than in monitored marine fish (9.9%), indicating longer-term contamination of freshwater fish species, especially in lakes. Higher radiocesium concentrations (maximum 18.7 kBq kg(-1)-wet in Oncorhynchus masou) were found in the northwestern areas from the FDNPP with higher deposition. However, radiocesium contamination levels were regarded as 1-2 orders of magnitude less than those after the Chernobyl accident. Lagged increase of (137)Cs concentration and longer ecological half-lives (Teco: 1.2-2.6 y in the central part of Fukushima Prefecture) were observed in carnivorous salmonids (O. masou, Salvelinus leucomaenis), whereas a rapid increase and decrease of (137)Cs concentration and shorter Teco (0.99 and 0.69 y) were found in herbivorous and planktivorous osmerids (Plecoglossus altivelis, Hypomesus nipponensis) with younger age at maturity. Comparison of Teco among salmonids, osmerids, and cyprinids suggests that, in addition to the fish feeding habits and life-cycles, hydraulic conditions in rivers and lakes (e.g., turnover time), which are expected to affect radiocesium concentration in prey items, are an important factor affecting the (137)Cs decreasing rate of freshwater fish.


Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts.
Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus inhibits invasion/metastasis of cancer cells. Here we studied its mechanism of action on human cervical cancer cells. The inhibition of cell invasion by rVP1 was accompanied with reduction in phosphatidylinositol (3,4,5)-triphosphate (PIP3), phospho-Akt S473, phosphorylated prohibitin (phospho-PHB) T258 in lipid rafts, dissociation of phospho-PHB T258 with Raf-1 and the inactivation of Raf-1/ERK. Addition of PIP3 or overexpression of constitutively active Akt and raft-anchored PHB T258 but not PHB T258I mutant protein reversed the inhibitory effects of rVP1. rVP1 inhibited cervical tumor growth and metastasis, and prolonged survival in xenograft mouse models. These results suggest that rVP1 inhibits cancer metastasis via de-phosphorylation of Akt and PHB T258 in lipid rafts to downregulate Raf/ERK signaling.


Sleep duration trajectories and all-cause mortality among Chinese elderly: A community-based cohort study.
China is among the largest and fastest aging countries. The elderly population is more vulnerable, with higher proportion of inappropriate sleep duration and risk of mortality, compared with young and middle-aged adults. Single-measured sleep duration has been associated with mortality, but the health effects of long-term sleep duration trajectories remain unknown. This study aimed to explore the prospective associations between sleep duration trajectories and all-cause mortality among Chinese elderly. Participants (n = 3,895; median age: 82 years; females: 53.3%) who reported sleep duration in all three surveys (2005, 2008, and 2011) from the community-based Chinese Longitudinal Healthy Longevity Survey (CLHLS) were followed up until 2019 (about 8 years). We identified sleep duration trajectories by latent class mixed model and explored their association with all-cause mortality using Cox hazard proportional regression and Laplace regression models. Further, stratified analysis by demographic characteristics and lifestyles and sensitivity analysis by lag effect, health-related factors, and inverse probability weighting were used to verify the robustness of the association. In addition, we explored the threshold effect of baseline sleep duration on the risk of all-cause mortality. We documented 1,881 all-cause deaths during 16,689 person-years of follow-up. Five sleep duration trajectories were identified: moderately increased trajectory (28.1%), rapidly increased trajectory (7.2%), persistent sleep trajectory of 7 h (33.7%), moderately decreased trajectory (21.3%), and rapidly decreased trajectory (9.7%). Compared with the persistent sleep trajectory of 7 h, the multivariable-adjusted HRs (95%CI) for moderately increased trajectory, rapidly increased trajectory, moderately decreased trajectory, and rapidly decreased trajectory were 1.21 (1.08, 1.36), 1.21 (1.01, 1.44), 0.95 (0.82, 1.10), and 0.93 (0.78, 1.11), respectively; and the corresponding difference in median survival time (95%CI) were -0.53 (-1.01, -0.05), -0.43 (0.16, -1.02), 0.26 (-0.34, 0.86), and 0.25 (-0.51, 1.02), respectively. Stratified and sensitivity analyses showed consistent results. Threshold analysis indicated a sharply increased risk of mortality in participants whose sleep exceeds 9 h (HR = 1.20, 95%CI: 1.11, 1.30). Compared with the persistent sleep trajectory of 7 h, moderately and rapidly increased sleep duration trajectories were associated with higher subsequent mortality in Chinese elderly. Those who report sleep exceeding 9 h may be at high risk for all-cause mortality.


T and B lymphocyte subpopulations and leukocyte terminal deoxynucleotidyl-transferase in energy-protein undernutrition.
Children with energy-protein undernutrition showed a reduction in the number of circulating T lymphocytes identified on the basis of their ability to form rosettes with sheep red blood cells. T cells with a receptor for IgM (Tmu) were decreased whereas T cells with a receptor for IgG (T gamma) were increased. Surface immunoglobulin bearing B cells were comparable in well nourished and malnourished subjects but the proportion of B alpha was increased in the latter. "Null" cells without the conventional markers of T or B cells were proportionately increased. Leukocyte terminal deoxynucleotidyl-transferase activity was elevated in the majority of undernourished children and correlated with the proportion of "null" cells. The significance of these observations is discussed and it is suggested that "null" cells represent immature undifferentiated T lymphocytes.


Moving in complex environments: a biomechanical analysis of locomotion on inclined and narrow substrates.
Characterisation of an organism's performance in different habitats provides insight into the conditions that allow it to survive and reproduce. In recent years, the northern quoll (Dasyurus hallucatus) - a medium-sized semi-arboreal marsupial native to northern Australia - has undergone significant population declines within open forest, woodland and riparian habitats, but less so in rocky areas. To help understand this decline, we quantified the biomechanical performance of wild northern quolls as they ran up inclined narrow (13 mm pole) and inclined wide (90 mm platform) substrates. We predicted that quolls may possess biomechanical adaptations to increase stability on narrow surfaces, which are more common in rocky habitats. Our results showed that quolls have some biomechanical characteristics consistent with a stability advantage on narrow surfaces. This includes the coupled use of limb pairs, as indicated via a decrease in footfall time, and an ability to produce corrective torques to counteract the toppling moments commonly encountered during gait on narrow surfaces. However, speed was constrained on narrow surfaces, and quolls did not adopt diagonal sequence gaits, unlike true arboreal specialists such as primates. In comparison with key predators, such as cats and dogs, northern quolls appear inferior in terrestrial environments but have a stability advantage at higher speeds on narrow supports. This may partially explain the heterogeneous declines in northern quoll populations among various habitats on mainland Australia.


A one-compartment single-pore model for extracorporeal hemoperfusion.
A one-compartment single-pore model is proposed for the dynamic analysis and performance evaluation of a hemoperfusion column under operation. Experimental data obtained from binary systems containing creatinine and uric acid may be well predicted by the theoretically computed curves. This theory offers a means for the preclinical evaluation of any prototype hemoperfusion column.


UDPglucose pyrophosphorylase from Xanthomonas spp. Characterization of the enzyme kinetics, structure and inactivation related to oligomeric dissociation.
The genes encoding for UDPglucose pyrophosphorylase in two Xanthomonas spp. were cloned and overexpressed in Escherichia coli. After purification to electrophoretic homogeneity, the recombinant proteins were characterized, and both exhibited similar structural and kinetic properties. They were identified as dimeric proteins of molecular mass 60kDa, exhibiting relatively high specific activity ( approximately 80Units/mg) for UDPglucose synthesis. Both enzymes utilized UTP or TTP as substrate with similar affinity. The purified Xanthomonas enzyme was inactivated after dilution into the assay medium. Studies of crosslinking with the bifunctional lysyl reagent bisuberate suggest that inactivation occurs by enzyme dissociation to monomers. UTP effectively protects the enzyme against inactivation, from which a dissociation constant of 15microM was calculated for the interaction substrate-enzyme. The UTP binding to the enzyme would induce conformational changes in the protein, favoring the subunits interaction to form an active dimer. This view was reinforced by protein modeling of the Xanthomonas enzyme on the basis of the prokaryotic UDPglucose pyrophosphorylase crystallographic structure. The in silico approach pointed out two main critical regions in the enzyme involved in subunit-subunit interaction: the region surrounding the catalytic-substrate binding site and the C-term.


Bactericidal permeability-increasing protein/LPS-binding protein (BPI/LBP) enhances resistance of golden pompano Trachinotus ovatus against bacterial infection.
Antimicrobial peptides are crucial components of innate immunity against microbial invasions. As a kind of antimicrobial peptides, bactericidal permeability-increasing protein (BPI)/lipopolysaccharide-binding protein (LBP) play vital roles in defending the host against gram-negative bacteria. In the current study, a novel BPI/LBP from Trachinotus ovatus (TroBPI/LBP) was characterized. The full length of TroBPI/LBP cDNA sequence is 1434 bp, which contained 477 amino acids. Multiple amino acid alignments of TroBPI/LBP shows 34.07%-84.49% identity with other fish BPI/LBP. Similar to other BPI/LBP, TroBPI/LBP also possesses an N-terminal signal peptide, a BPI/LBP/CETP N-terminal domain, and a BPI/LBP/CETP C-terminal domain. In vitro, the recombinant protein of TroBPI/LBP showed effective bacterial depression activity and binding activity to gram-negative bacteria. In vivo, TroBPI/LBP was constitutively expressed in tested tissues, and the highest expression level was in liver. Following Vibrio alginolyticus stimulation, the mRNA expression of TroBPI/LBP was significantly upregulated in immune-related tissues, and peaked at 12 h post-infection, which confirmed that TroBPI/LBP was highly sensitive to V. alginolyticus stimuli. Furthermore, functional analyses showed that the overexpression of TroBPI/LBP could enhance the ability of fish to against V. alginolyticus infection, and the knockdown of TroBPI/LBP significantly diminished bacterial clearance capacity post-infection. Therefore, these results suggest that TroBPI/LBP may play an important role in host defense against bacterial infection.


EVALUATION OF THERMOTOLERANT ACETOBACTER PASTEURIANUS STRAINS ISOLATED FROM MOROCCAN FRUITS CATALYZING OXIDATIVE FERMENTATION AT HIGH TEMPERATURE.
Six strains of acetic acid bacteria were isolated from Moroccan local products and their potential as industrial strains was evaluated in lab-bioreactor. Three of them, namely TAV01, AF01 and CV01, isolated from traditional apple vinegar, apple and cactus fruit, respectively were selected and their responses to high temperature were assessed. Morphological and biochemical identification confirmed that these strains belong to Acetobacter species. Their growth and acetic acid production were compared with the thermoresistant reference strain, Acetobacter senegalensis and mesophilic strains of Acetobacter pasteurianus. The two strains AF01 and CV01 showed abundant growth and noticeable acetic acid production ability at high temperatures (38 to 41°C). A thermophilic character was observed for AF01 strain. Indeed, this bacterium grew better at 38 than 30°C.


Treatment and prognosis of leptomeningeal disease secondary to metastatic breast cancer: A single-centre experience.
Leptomeningeal disease (LMD) is an uncommon complication of advanced breast cancer. The prognosis is poor, and although radiotherapy (RT), systemic and intra-thecal (IT) chemotherapy are accepted treatment modalities, efficacy data are limited. This study was designed to evaluate potential predictors of survival in this patient group. Breast cancer patients with LMD diagnosed by MRI in a 10-year period (2004-2014) were identified from electronic patient records. PFS and OS estimates were calculated using Kaplan-Meier method, with planned sub-group analysis by treatment modality. Cox regression was employed to identify significant prognostic variables. We identified 182 eligible patients; all female, median age at LMD diagnosis 52.5 years (range 23-80). Ninety patients (49.5%) were ER positive/HER2 negative; 48 (26.4%) were HER2 positive, and 27 (14.8%) were triple negative. HER2 status was unknown in 17 (9.3%). Initial management of LMD was most commonly whole or partial brain RT in 62 (34.1%), systemic therapy in 45 (24.7%) or supportive care alone in 37 (20.3%). Fourteen patients (7.7%) underwent IT chemotherapy, of whom two also received IT trastuzumab. From diagnosis of LMD, the median PFS was 3.9 months (95%CI 3.2-5.0) and median OS was 5.4 months (95%CI 4.2-6.6). Patients treated with systemic therapy had the longest OS (median 8.8 months, 95%CI 5.5-11.1), compared to RT; 6.1 months (95%CI 4.2-7.9 months), IT therapy; 2.9 months (95%CI 1.2-5.8) and supportive care; 1.7 months (95%CI 0.9-3.0). On multivariable analysis, triple negative histology, concomitant brain metastases, and LMD involving both the brain and spinal cord were associated with poor OS. Breast cancer patients with triple negative LMD, concomitant brain metastases or LMD affecting both the spine and brain have the poorest prognosis. Clinical trials to identify more effective treatments for these patients are urgently needed.


Sino nasal inhalation of isotonic versus hypertonic saline (6.0%) in CF patients with chronic rhinosinusitis - Results of a multicenter, prospective, randomized, double-blind, controlled trial.
Chronic rhinosinusitis is a hallmark of Cystic fibrosis (CF) impairing the patients' quality of life and overall health. However, therapeutic options have not been sufficiently evaluated. Bronchial inhalation of mucolytic substances is a gold standard in CF therapy. Previously, we found that sinonasal inhalation of dornase alfa as vibrating aerosol reduces symptoms of chronic rhinosinusitis more effectively than NaCl 0.9% (net treatment benefit: -5.87±2.3 points, p=0.017; SNOT-20 total score). This multicenter study compares the effect of NaCl 6.0% vs. NaCl 0.9% following the protocol from our preceding study with dornase alfa. Sixty nine CF patients with chronic rhinosinusitis in eleven German CF centers were randomized to receive sinonasal vibrating inhalation of either NaCl 6.0% or NaCl 0.9% for 28days. After 28days of wash-out, patients crossed over to the alternative treatment. The primary outcome parameter was symptom score in the disease-specific quality of life Sino-Nasal Outcome Test-20 (SNOT-20). Additionally, pulmonary function was assessed, as well as rhinomanometry and inflammatory markers in nasal lavage (neutrophil elastase, interleukin (IL)-1β, IL-6, and IL-8) in a subgroup. Both therapeutic arms were well tolerated and showed slight improvements in SNOT-20 total scores (NaCl 6.0%: -3.1±6.5 points, NaCl 0.9%: -5.1±8.3 points, ns). In both treatment groups, changes of inflammatory parameters in nasal lavage from day 1 to day 29 were not significant. We suppose that the irritating properties of NaCl 6.0% reduced the suitability of the SNOT-20 scores as an outcome parameter. Alternative primary outcome parameters such as MR-imaging or the quantity of sinonasal secretions mobilized with both saline concentrations were, however, not feasible. Sinonasal inhalation with NaCl 6.0% did not lead to superior results vs. NaCl 0.9%, whereas dornase alfa had been significantly more effective than NaCl 0.9%.


Quantitative chiral analysis in capillary electrophoresis from unresolved peaks using derivative electropherograms, experimental design, and artificial neural networks.
Quantitative capillary electrophoretic analysis of chiral compounds might be difficult or even impossible when baseline separation is not reached. In this work, the use of n-th derivative of the electropherogram was studied and examined on model and experimental data. The electropherograms should be first smoothed using Savitzky-Golay method and the quantitative analysis is then possible using either a graphical method or multivariate calibration applying a combination of experimental design (ED) and artificial neural networks (ANNs). The best results were obtained for the first derivative, higher derivatives are not suitable because of noise accumulation. The method was applied to real experimental data to quantify chiral amino acids from unresolved peaks, but it is applicable for quantitative analysis of any other chiral analytes from poorly resolved peaks. Precision of analysis from partially resolved peaks reached was about +/- 3.2% relative standard deviation.


Enhanced MRI and MRI-guided interventional procedures in women with asymptomatic silicone-injected breasts.
Asymptomatic women who have received silicone injection for breast augmentation have a risk of underestimating breast cancer by palpation, mammography, or breast sonography. Enhanced breast MRI is sensitive to display certain nonspecific enhanced lesions or suspicious lesions. Such nonspecific MRI-detected lesions could be managed by American College Radiology BI-RADS lexicon and selectively with MRI-guided techniques biopsy to prevent unnecessary surgery.


Valve ring abscess in infective endocarditis: visualization with wide angle two dimensional echocardiography.
Two dimensional echocardiography permitted visualization of a valve ring abscess complicating infective endocarditis in four patients. Abscess formation was defined as an echo-free cavity within tissues surrounding the infected valve. Abscess in the valve ring extended into the perivalvular structures, including the upper ventricular septum (one patient), left ventricular myocardium (one patient) and contiguous fibrous structures (three patients). Two dimensional echocardiography is the only noninvasive technique for direct visualization of the abscess cavity complicating infective endocarditis and may allow better appreciation of incidence, evolution and natural (or unnatural) course of this heretofore seldom recognized complication of infective endocarditis.


Mutant p53 in bone marrow stromal cells increases VEGF expression and supports leukemia cell growth.
Genetic alterations, including p53 mutations, have been identified in the stroma of solid tumors and are thought be involved in the induction of tumor growth and metastasis. We tested the hypothesis that somatic molecular alterations in bone marrow stromal cells provide a favorable growth environment for leukemic cells. We established an in vitro model consisting of stroma expressing mutant p53 (Cys135Ser) to study its ability to support growth of cells from a pre-B acute lymphoblastic leukemia (ALL) cell line. Normal and leukemic bone marrow stromal cells were screened for p53 mutations by mutant-specific ELISA, SSCP, and direct sequencing. Secretion of vascular endothelial growth factor (VEGF) was measured by quantitative ELISA. Transfection of stromal cells with mutant p53 increased synthesis of VEGF and supported the growth of leukemic cells. An ELISA-based assay suggested the occurrence of in vivo p53 alterations in bone marrow stromal cells from 2 of 12 ALL patients screened. Direct sequencing of one of these samples revealed a somatic heterozygous p53 gene mutation (Asp49His). This sample secreted more VEGF and provided increased growth support to leukemic cells. The ability of Asp 49His-p53 to increase the expression of VEGF was confirmed with transfection experiments in a p53-null cell line. Our findings indicate that genetic alterations, such as p53 mutations, in stromal cells can increase stromal-derived support of leukemia growth. Increased synthesis of pro-angiogenic cytokines, such as VEGF, may constitute one possible pathway by which this process is mediated.


The B55α subunit of PP2A drives a p53-dependent metabolic adaptation to glutamine deprivation.
Glutamine is an essential nutrient for cancer cell survival and proliferation, yet the signaling pathways that sense glutamine levels remain uncharacterized. Here, we report that the protein phosphatase 2A (PP2A)-associated protein, α4, plays a conserved role in glutamine sensing. α4 promotes assembly of an adaptive PP2A complex containing the B55α regulatory subunit via providing the catalytic subunit upon glutamine deprivation. Moreover, B55α is specifically induced upon glutamine deprivation in a ROS-dependent manner to activate p53 and promote cell survival. B55α activates p53 through direct interaction and dephosphorylation of EDD, a negative regulator of p53. Importantly, the B55α-EDD-p53 pathway is essential for cancer cell survival and tumor growth under low glutamine conditions in vitro and in vivo. This study delineates a previously unidentified signaling pathway that senses glutamine levels as well as provides important evidence that protein phosphatase complexes are actively involved in signal transduction.


Expression of heterobispecific antibodies by genes transfected into producer hybridoma cells.
We report the expression of heterobispecific antibodies (Ab) by transferred genes. The kappa and gamma 1 genes of a mouse anti-idiotypic Ab (IgG1) were transfected into a mouse hybridoma cell line secreting Ab (IgG1), directed against an isoenzyme of human creatine kinase. Stable cell lines secreting the parental Ab derived from the introduced genes and a mixture of hybrid Ab were established. The transfected Ab specificity was expressed at similar levels as in a nonproducer background (50 ng-1 microgram/ml), heterobispecific Ab was expressed in microgram quantities (1-4 micrograms/ml) in all cell lines examined. As shown by isoelectric focusing analysis, hybrid Ab (heterobifunctional and other species) are expressed to a similar extent in the transfected cell lines as the Ab in the parental Ab-producing cells.


Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal.
When stem cells divide, they can generate progeny with the same developmental potential as the original cell, a process referred to as self-renewal. Self-renewal is driven intrinsically by gene expression in a cell-type-specific manner and is modulated through interactions with extrinsic cues from the environment, such as growth factors. However, despite the prevalence of the term self-renewal in the scientific literature, this process has not been defined at the molecular level. Haematopoietic stem cells are an excellent model for the study of self-renewal because they can be isolated prospectively, manipulated relatively easily and assessed by using well-defined assays. Establishing the principles of self-renewal in haematopoietic stem cells will lead to insights into the mechanisms of self-renewal in other tissues.


Predictors of personal air concentrations of chloroform among US adults in NHANES 1999-2000.
Volunteer studies suggest that showering/bathing with chlorinated tap water contributes to daily chloroform inhalation exposure for the majority of US adults. We used data from the 1999-2000 US National Health and Nutrition Examination Survey (NHANES) and weighted multiple linear regression to test the hypothesis that personal exposure microevents such as showering or spending time at a swimming pool would be significantly associated with chloroform levels in 2-3 day personal air samples. The NHANES data show that eight of 10 US adults are exposed to detectable levels of chloroform. Median (1.13 microg/m(3)), upper percentile (95th, 12.05 microg/m(3)), and cancer risk estimates were similar to those from recent US regional studies. Significant predictors of log personal air chloroform in our model (R(2)=0.34) included age, chloroform concentrations in home tap water, having no windows open at home during the sampling period, visiting a swimming pool during the sampling period, living in a mobile home/trailer or apartment versus living in a single family (detached) home, and being Non-Hispanic Black versus Non-Hispanic White, although the race/ethnicity estimates appear influenced by several outlying observations. Reported showering activity was not a significant predictor of personal air chloroform, possibly due to the wording of the NHANES shower question. The NHANES measurements likely underestimate true inhalation exposures since subjects did not wear sampling badges while showering or swimming, and because of potential undersampling by the passive monitors. Research is needed to quantify the potential difference.


Effects of kainic acid lesions of the striatum on self-stimulation in the substantia nigra and ventral tegmental area.
Unilateral kainic acid lesions of the dorsal striatum provided evidence for a dissociation of neural substrates of brain-stimulation reward at sites in the ventral tegmental area and substantia nigra. The lesions caused a significant increase in current intensity thresholds at substantia nigra placements, whereas similar lesions had no effect on self-stimulation thresholds at sites in the ventral tegmentum. In addition, the rate-increasing effects of D-amphetamine (0.1-1.0 mg/kg) on self-stimulation were determined before and after lesions to the dorsal striatum. No significant changes in dose-response curves were observed at either loci. Amphetamine-induced rotation was used to confirm damage to the dorsal striatum and lesioned animals were observed to rotate towards the side of the lesion. In contrast, sham-lesioned animals showed turning away from the side stimulated electrically in previous tests. The results of the self-stimulation and rotation experiments are discussed in the context of neural substrates of reward and motor activity.


Identification of a plasma membrane protein involved in Pi transport in the yeast Candida tropicalis.
A plasma membrane protein was found to contain antigenic determinants in common with a Pi-binding protein released by osmotic shock from Candida tropicalis. This plasma membrane protein (M.P. 30) has a molecular mass of 30 kDa as measured by SDS-PAGE and anti-M.P. 30 antibodies inhibit Pi uptake in protoplasts while only the corresponding Fab fragments inhibit Pi transport in whole cells. This plasma membrane protein may be the Pi plasma membrane carrier.


Enamel surface roughness after debonding of orthodontic brackets and various clean-up techniques.
This study aimed to evaluate enamel roughness after adhesive removal using different burs and an Er:YAG laser. The buccal surfaces of forty human premolars were sealed by two layers of nail varnish, except for a circular area of 3 mm in diameter on the middle third. The enamel surfaces were initially subjected to profilometry analysis and four parameters of surface irregularity (Ra, Rq, Rt and Rz) were recorded. Following bracket bonding and debonding, adhesive remnants were removed by tungsten carbide burs in low- or high- speed handpieces (group 1 and 2, respectively), an ultrafine diamond bur (group 3) or an Er:YAG laser (250 mJ, long pulse, 4 Hz) (group 4), and surface roughness parameters were measured again. Then, the buccal surfaces were polished and the third profilometry measurements were performed. The specimens that were cleaned with a low speed tungsten carbide bur showed no significant difference in surface irregularity between the different treatment stages (p>0.05). Surface roughness increased significantly after clean-up with the diamond bur and the Er:YAG laser (p<0.01). In comparison between groups, adhesive removal with tungsten carbide burs at slow- or high-speed handpieces produced the lowest, while enamel clean-up with the Er:YAG laser caused the highest values of roughness measurements (P<0.05). Under the study conditions, application of the ultrafine diamond bur or the Er:YAG laser caused irreversible enamel damage on tooth surface, and thus these methods could not be recommended for removing adhesive remnants after debonding of orthodontic brackets.


Retinal and choroidal vascular features in patients with retinitis pigmentosa imaged by OCT based microangiography.
To image vascular features of retinitis pigmentosa (RP) using optical coherence tomography angiography (OCTA). Patients with RP were imaged by spectral domain optical coherence tomography based angiography (OCTA). The optical microangiography (OMAG) algorithm was applied to scanned datasets to generate 3D OCTA retinal angiograms, i.e., OMAG angiograms. Motion tracking was used to minimize artifacts due to eye movement, and large field of view OMAG angiograms were achieved through a montage scanning protocol. For better visualization, depth volumes were segmented to separate the superficial retinal layers from deep outer retinal layers. The choriocapillaris and other choroidal layers were also segmented. To investigate the changes in retinal architecture, the inner segment/outer segment (IS/OS) junction to RPE layer was segmented to generate en face structural images through averaging intensity projection. Color fundus images and/or Goldmann visual fields were available for comparison of the findings to OMAG images. A total of 25 eyes (13 patients, seven women and six men) diagnosed with RP at various stages were enrolled in this study from October 2014 to January 2016 and imaged by OCTA. The resulting OMAG angiograms provided detailed visualization of retinal and choroidal vascular networks presented within the retina and choroid in a large field of view (FOV) (∼6.7 mm × 6.7 mm). All patients with a severity score greater than 3 showed abnormal microvasculature in both deep retinal and choroidal layers on OMAG images. Images of patients with a score of 4 indicating only peripheral abnormalities demonstrated relatively normal vasculature networks. Microvascular changes in the retinal and choroidal vasculature correlate with structural changes in the slab from IS/OS junction to RPE layer. OCTA is useful in evaluating the microvascular changes in a large FOV encompassing the maculae of patients with RP. The large FOV of OMAG angiograms, enabled by the motion tracking, provides visualization of high definition and high resolution microvascular networks at varying stages of RP. Microvascular imaging may have significant utility in the diagnosis and monitoring of disease progression in RP patients.


Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC. We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA. Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001). Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.


Prognostic impact of residual SYNTAX score in patients with obstructive sleep apnea and acute coronary syndrome: a prospective cohort study.
There is a paucity of data from large prospective study evaluating the prognostic significance of the residual Synergy between percutaneous intervention with Taxus drug-eluting stents and cardiac surgery (SYNTAX) Score (rSS) in patients with obstructive sleep apnea (OSA) and Acute Coronary Syndrome (ACS). ACS patients who undergoing percutaneous coronary angiography and completing a sleep study during hospitalization were prospectively enrolled. The baseline SYNTAX Score (bSS) and the rSS after revascularization were assessed. Complete revascularization (CR, rSS = 0) and incomplete revascularization (ICR, rSS > 0) were categorized. OSA (apnea hypopnea index, AHI ≥ 15) and non-OSA (AHI < 15) were grouped according to AHI. The primary endpoint of the study was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for UAP or heart failure. Overall, 752 patients were prospectively enrolled. At a median follow-up of 1 year, the incidence of MACCEs was significantly higher in the OSA than in the non-OSA group (hazard ratio [HR]:1.68; 95% confidence interval [CI]:1.04-2.72; P = .034). ICR was associated with a higher risk of MACCEs in the non-OSA group (HR:3.34;95% CI:1.0-11.12; P = .05). The OSA patients with ICR had a 5.1 higher risk of MACCEs compared with the non-OSA with CR group, P = .007. The OSA patients with CR had a similar 1-year MACCEs as all the non-OSA patients (HR:1.10; 95% CI:0.515-2.349; P = 0.806). ACS patients with OSA and ICR have a high rate of MACCEs at 1 year. In contrast, the prognosis of ACS patients with OSA but CR is favorable and similar to patients without OSA. Adequate level of revascularization is recommended to optimize clinical outcomes in ACS patients with OSA. Clinicaltrials.gov identifier NCT03362385.


Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene on ventricular arrhythmia vulnerability in a rabbit heart model.
Following long-duration ventricular fibrillation (LDVF), reinitiation of ventricular fibrillation (VF) poses a major challenge during resuscitation. Ryanodine receptor 2 (RyR2) becomes dysfunctional following VF. The relationship between LDVF, RyR2 modulation, and ventricular refibrillation, as well as the role of RyR2 phosphorylation, remains unknown. Langendorff-perfused rabbit hearts were subjected to global ischemia and treated with azumolene (or vehicle alone in controls) upon reperfusion. After electrical induction of an initial LDVF episode, each heart was further stimulated electrically to assess reinducibility of VF. Myocardial calcium dynamics were assessed by optical mapping. RyR2 phosphorylation in left ventricular tissue extracts was analyzed by Western blot analysis. Fewer episodes of refibrillation (lasting ≥ 10 seconds) were induced in azumolene-treated hearts than in controls (P = 0.01); however, this reduction in refibrillation was abrogated in the presence of the protein kinase A inhibitor H89. Spontaneous calcium elevation was significantly lower in azumolene-treated hearts than in control hearts ( P = 0.002) and in hearts pretreated with H89 before azumolene ( P = 0.01). RyR2 phosphorylation at Ser2808 was higher in hearts subjected to LDVF than in non-VF hearts ( P = 0.029), while no significant difference was found at Ser2814. Pretreatment with H89 led to significantly less RyR2 phosphorylation at Ser2808 ( P = 0.04) after LDVF, while pretreatment with KN93 or azumolene alone showed no effects on RyR2 phosphorylation. Ventricular refibrillation following LDVF was reduced by azumolene, which also improves calcium dynamics. RyR2 phosphorylation at Ser2808 is a prerequisite for the beneficial effects of azumolene.


Rare Mutations in AHDC1 in Patients with Obstructive Sleep Apnea.
Obstructive sleep apnea (OSA) is a common disorder influenced by genetic and environmental factors. Mutations of AT-hook DNA-binding motif containing 1 (AHDC1) gene have been implicated which could cause rare syndromes presenting OSA. This study aims to investigate some rare mutations of AHDC1 in Chinese Han individuals with OSA. Three hundred and seventy-five patients with OSA and one hundred and nine control individuals underwent polysomnography. A targeted sequencing experiment was taken in 100 patients with moderate-to-severe OSA, and genotyping was taken in 157 moderate-to-severe OSA and 100 control individuals. The effect of mutations was validated by the luciferase reporter assay. One rare missense mutation (AHDC1: p.G1484D) and two mutations (c.-88C>T; c.-781C>G) in 5'-untranslated region (UTR) of AHDC1 were identified. The rare mutation (c.-781C>G) in 5'-UTR that was identified in several patients presenting more severe clinical manifestations affects expression of AHDC1. Conclusions. Our results revealed three rare mutations of AHDC1 in patients with OSA in Chinese Hanindividuals.


Clinicopathological features of salivary and non-salivary adenoid cystic carcinomas.
Adenoid cystic carcinoma (ACC), commonly from salivary glands, is known for its insidious local growth and usually protracted clinical course. ACC developing from non-salivary glands (i.e., non-salivary ACC) is heterogeneous, and its clinicopathological features remain poorly defined. Patients treated for ACC in a single institution between 1995 and 2007 were included in this study. Immunohistochemical evaluation of Ki-67, E-cadherin, p16, and cyclinD1 was performed. The prognostic significance of clinical and immunophenotypic markers was evaluated. 83 cases of salivary ACC and 24 cases of non-salivary ACC were included. The expression levels of Ki-67 (54.8%), E-cadherin (90.4%), p16 (32.9%), and cyclinD1 (19.2%) between ACCs present at various sites were not different. Sinonasal, lacrimal, and tracheobronchial ACCs had significantly worse outcomes than those of ACC of the major salivary glands. Postoperative radiotherapy reduced the recurrence rate of patients with a negative resection margin (P=0.028). Older age (age >60 years), advanced stage, positive resection margin, high histological grade, and high expression of Ki-67 were significantly correlated with poor prognosis. In conclusion, the site of origin plays a role in the prognosis of ACC, in which positive resection margin and advanced stage are possible factors underlying the differences in outcomes.


Embolization of renal vascular lesions: clinical experience with microcoils and tracker catheters.
After biopsy (n = 6) and nephrostomy (n = 1) of three native and four transplanted kidneys, gross hematuria, hypertension, and deterioration of function necessitated performance of transarterial embolization. Angiography revealed five arteriovenous fistulas (AVFs), one pseudoaneurysm, and one arteriocaliceal fistula. Superselective catheterization was accomplished using 5 Fr standard diagnostic catheters and 3 Fr coaxial Tracker catheters. Four of five AVFs were embolized successfully by inserting unfibered (2 patients) and fibered (2 patients) platinum coils (diameters 2 mm and 4 mm, respectively). For one AVF, additional injection of butylcyanoacrylate was necessary. The pseudoaneurysm was embolized successfully by such injection, and the arteriocaliceal fistula was occluded using one unfibered 2-mm coil. Embolization stopped the bleeding in all patients. One week after treatment, renal function was improved in 5 patients and remained unaffected in 2. Superselective embolization using Tracker catheters and fibered microcoils is an effective, safe treatment of renal vascular lesions.


Botulinum toxin for dysphagia due to cricopharyngeal dysfunction.
Botulinum injection in the cricopharyngeal muscle has not yet been described thoroughly. In reviewing the literature, only 24 cases were found in which botulinum injection was used to treat cricopharyngeal dysfunction. We want to add another four cases and discuss specific indications and necessary pre-treatment examinations. Depending on the patient's history and the clinical findings, botulinum injection may be performed. Manometry and videofluoroscopy are not mandatory. The type of functional pathology defines whether botulinum toxin will be a definite treatment or a temporary relief.


Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira(®) in healthy subjects.
The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of the proposed adalimumab biosimilar MSB11022 (Merck) with Humira(®) (AbbVie), sourced from both the US (US reference product [US-RP]) and Europe (European reference medicinal product [EU-RMP]). In this phase 1 double-blind, parallel group trial (EMR200588-001), 213 healthy volunteers were randomized 1 : 1 : 1 to receive a single dose (40 mg) of MSB11022, US-RP or EU-RMP in order to achieve 80% power assuming a 5% difference among groups and a 10% dropout rate. Following a preplanned blinded sample size re-assessment after more than 50% of the originally planned subjects had been observed, the sample size was increased to 237 (79 per arm) to ensure 213 completers. Primary PK endpoints analyzed by non-compartmental methods, were area under the curve (AUC) from time 0 extrapolated to infinity (AUC(0,∞)), maximum observed concentration (Cmax ), and AUC from time 0 to the last quantifiable concentration (AUC(0,tlast )). PK equivalence was declared if the 90% CI for the test : reference ratio lay within the 80-125% equivalence margin. Bioequivalence was demonstrated if all three PK parameters met the PK equivalence criteria. Safety and tolerability were also evaluated. Mean serum concentration-time profiles for the three treatments were similar. MSB11022 demonstrated PK equivalence to US-RP and EU-RMP for all primary endpoints. The geometric means of AUC(0,∞), Cmax and AUC(0,tlast ) following a single dose of MSB11022 were 2276.05 μg ml(-1) h, 3.44 μg ml(-1) and 1983.90 μg ml(-1) h, respectively. Adverse events (AEs) were similar across all groups, with treatment-emergent AEs (TEAEs) reported by 62.8%, 56.3% and 62.0% of subjects within the MSB11022, US-RP and EU-RMP groups, respectively. Most of the TEAEs were considered mild and unrelated to study drug. No deaths or severe AEs related to the study drug were reported. Bioequivalence between MSB11022, US-RP and EU-RMP was demonstrated. Safety, tolerability and immunogenicity profiles were similar between subjects receiving MSB11022 and US-RP or EU-RMP. These data support the further clinical evaluation of MSB11022 as a proposed biosimilar of adalimumab.


De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: a genomics approach to personalized medicine.
Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4-6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood. These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient's cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes.


Evaluating the impact of implementing public bicycle share programs on cycling: the International Bikeshare Impacts on Cycling and Collisions Study (IBICCS).
Despite rapid expansion of public bicycle share programs (PBSP), there are limited evaluations of the population-level impacts of these programs on cycling, leaving uncertainty as to whether these programs lead to net health gains at a population level or attract those that already cycle and are sufficiently physically active. Our objective was to determine whether the implementation of PBSPs increased population-level cycling in cities across the US and Canada. We conducted repeat cross-sectional surveys with 23,901 residents in cities with newly implemented PBSPs (Chicago, New York), existing PBSPs (Boston, Montreal, Toronto) and no PBSPs (Detroit, Philadelphia, Vancouver) at three time points (Fall 2012, 2013, 2014). We used a triple difference in differences analysis to assess whether there were increases in cycling over time amongst those living in closer proximity (< 500 m) to bicycle share docking stations in cities with newly implemented and existing PBSPs, relative to those in cities with no PBSPs. Living in closer proximity to bicycle share predicted increases in cycling over time for those living in cities with newly implemented PBSPs at 2-year follow-up. No change was seen over time for those living in closer proximity to bicycle share in cities with existing PBSPs relative to those in cities with no PBSP. These findings indicate that PBSPs are associated with increases in population-level cycling for those who live near to a docking station in the second year of program implementation.


Impact of free hypertension pharmacy program and social distancing policy on stroke: A longitudinal study.
The estimated lifetime risk of stroke was the highest in East Asia worldwide, especially in China. Antihypertensive therapy can significantly reduce stroke mortality. However, blood pressure control is poor. Medication adherence is a barrier as patients' out-of-pocket costs have risen. We aimed to take advantage of a free hypertension pharmacy intervention and quantified the impact on stroke mortality. A free pharmaceutical intervention program was implemented in Deqing, Zhejiang province in April 2018. Another non-pharmaceutical intervention, social distancing due to the pandemic of Coronavirus disease 2019 (COVID-19), was also key to affecting stroke mortality. We retrospectively collected the routine surveillance data of stroke deaths from Huzhou Municipal Center for Disease Prevention and Control in 2013-2020 and obtained within-city mobility data from Baidu Migration in 2019-2020, then we quantified the effects of both pharmaceutical intervention and social distancing using Serfling regression model. Compared to the predicted number, the actual number of stroke deaths was significantly lower by 10% (95% CI, 6-15%; p < 0.001) from April 2018 to December 2020 in Deqing. Specifically, there was a reduction of 19% (95% CI, 10-28%; p < 0.001) in 2018. Moreover, we observed a 5% (95% CI, -4 - 14%; p = 0.28) increase in stroke mortality due to the adverse effect of COVID-19 but it wasn't statistically significant. Free hypertension pharmacy program has great potential to prevent considerable stroke deaths. In the future, the free supply of low-cost, essential medications that target patients with hypertension at increased risk of stroke could be taken into account in formulating public health policies and guiding allocations of health care resources.


Testicular tumors: oncologic imaging and diagnosis.
The extreme radiosensitivity of testicular seminomas plus recent advances in chemotherapy for nonseminomatous tumors and for advanced seminomas have made long term survival possible in the large majority of patients with testis cancer. Since choice of therapy is determined by tumor histology and extent of disease, accurate clinical staging is critical. Computed tomography (CT) of the abdomen and chest is the imaging procedure of choice for staging testis cancer. Clinical staging accuracy of 80 to 90% can be achieved using CT in combination with radioimmunoassays for beta-HCG and AFP. Ultrasonography (US), while less sensitive and specific than CT for determining nodal status, may be useful in thin patients with sparse retroperitoneal fat; in addition US may play an important role in detecting occult testicular neoplasms and in assessing primary tumor extent within the scrotum. Lymphangiography should be reserved for Stage I patients in whom elective treatment of the retroperitoneum is not planned. Follow-up should include serial radioimmunoassays for serum AFP and beta-HCG and periodic CT examinations of the abdomen and chest. Technical improvements in CT scanners and further experience with the use of tumor markers should help refine our ability to stage and manage patients with testicular tumors. In addition, nuclear magnetic resonance (NMR) imaging and radionuclide imaging following injection of radioactively labelled antibodies to AFP and beta-HCG are new techniques which offer great promise for the future.