Towards high-energy and durable lithium-ion batteries via atomic layer deposition: elegantly atomic-scale material design and surface modification.
Targeted at fueling future transportation and sustaining smart grids, lithium-ion batteries (LIBs) are undergoing intensive investigation for improved durability and energy density. Atomic layer deposition (ALD), enabling uniform and conformal nanofilms, has recently made possible many new advances for superior LIBs. The progress was summarized by Liu and Sun in their latest review [1], offering many insightful views, covering the design of nanostructured battery components (i.e., electrodes and solid electrolytes), and nanoscale modification of electrode/electrolyte interfaces. This work well informs peers of interesting research conducted and it will also further help boost the applications of ALD in next-generation LIBs and other advanced battery technologies.


The effects of chlordiazepoxide, amphetamine and cocaine on bar-press behavior in normal and genetically nervous dogs.
Studies on two strains of pointer dogs have demonstrated that administration of a benzodiazepine (chlordiazepoxide) facilitates acquisition of goal-directed behavior in "genetically nervous" subjects. Continued admistration of the drug is required to maintain barpress response in this strain of dogs. The concomitant administration of either cocaine or amphetamine, compounds which inhibit neuronal reuptake of norepinephrine, disrupts the behavioral response of the genetically nervous E-strain subjects to a far greater extent than the stable A-strain subjects. It is also shown that after 14 days of daily administration of chlordiazepoxide, withdrawal of the drug not only re-results in almost complete loss of bar-press response in the E-strain subjects but also results in a temporary decrease in the acquired behavioral response of the stable A-strain subjects.


On optimal coupling of the 'electronic photoreceptors' into the degenerate retina.
To restore sight in atrophic age-related macular degeneration, the lost photoreceptors can be replaced with electronic implants, which replicate their two major functions: (1) converting light into an electric signal, and (2) transferring visual information to the secondary neurons in the retinal neural network—the bipolar cells (BC). We study the selectivity of BC activation by subretinal implants and dynamics of their response to pulsatile waveforms in order to optimize the electrical stimulation scheme such that retinal signal processing with 'electronic photoreceptors' remains as close to natural as possible. A multicompartmental model of a BC was implemented to simulate responses of the voltage-gated calcium channels and subsequent synaptic vesicle release under continuous and pulsatile stimuli. We compared the predicted response under various frequencies, pulse durations, and alternating gratings to the corresponding experimental measurements. In addition, electric field was computed for various electrode configurations in a 3-d finite element model to assess the stimulation selectivity via spatial confinement of the field. The modeled BC-mediated retinal responses were, in general, in good agreement with previously published experimental results. Kinetics of the calcium pumps and of the neurotransmitter release in ribbon synapses, which underpin the BC's temporal filtering and rectifying functions, allow mimicking the natural BC response with high frequency pulsatile stimulation, thereby preserving features of the retinal signal processing, such as flicker fusion, adaptation to static stimuli and non-linear summation of subunits in receptive field. Selectivity of the BC stimulation while avoiding direct activation of the downstream neurons (amacrine and ganglion cells—RGCs) is improved with local return electrodes. If the retinal neural network is preserved to a large extent in age-related macular degeneration, selective stimulation of BCs with proper spatial and temporal modulation of the extracellular electric field may retain many features of the natural retinal signal processing and hence allow highly functional restoration of sight.


ESOPHAGEAL CARCINOMA: IS SQUAMOUS CELL CARCINOMA DIFFERENT DISEASE COMPARED TO ADENOCARCINOMA? A transversal study in a quaternary high volume hospital in Brazil.
Esophageal cancer is one of the leading causes of mortality among the neoplasms that affect the gastrointestinal tract. There are several factors that contribute for development of an epidemiological esophageal cancer profile in a population. This study aims to describe both clinically and epidemiologically the population of patients with diagnosis of esophageal cancer treated in a quaternary attention institute for cancer from January, 2009 to December, 2011, in Sao Paulo, Brazil. The charts of all patients diagnosed with esophageal cancer from January, 2009, to December, 2011, in a Sao Paulo (Brazil) quaternary oncology institute were retrospectively reviewed. Squamous cell cancer made up to 80% of the cases of esophageal cancer. Average age at diagnosis was 60.66 years old for esophageal adenocarcinoma and 62 for squamous cell cancer, average time from the beginning of symptoms to the diagnosis was 3.52 months for esophageal adenocarcinoma and 4.2 months for squamous cell cancer. Average time for initiating treatment when esophageal cancer is diagnosed was 4 months for esophageal adenocarcinoma and 4.42 months for squamous cell cancer. There was a clear association between squamous cell cancer and head and neck cancers, as well as certain habits, such as smoking and alcoholism, while adenocarcinoma cancer showed more association with gastric cancer and gastroesophageal reflux disease. Tumoral bleeding and pneumonia were the main causes of death. No difference in survival rate was noted between the two groups. Adenocarcinoma and squamous cell carcinoma are different diseases, but both are diagnosed in advanced stages in Brazil, compromising the patients' possibilities of cure.


SOX2 knockdown inhibits the migration and invasion of basal cell carcinoma cells by targeting the SRPK1-mediated PI3K/AKT signaling pathway.
Basal cell carcinoma (BCC) is the most common type of human skin cancer, which is driven by the aberrant activation of Hedgehog signaling. Previous evidence indicated that sex determining region Y-box 2 (SOX2) is associated with the tumor metastasis. However, the expression and role of SOX2 in BCC remain unknown. Therefore, the aim of the current study was to analyze the possible mechanism of SOX2 in the progression of BCC. The levels of SOX2 in BCC cells were detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were also used to determine the migration and invasion of BCC cells. Immunoblotting and immunofluorescence were used for analyzing the role of SOX2 knockdown in the serine-arginine protein kinase 1 (SRPK1)-mediated phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in BCC cells. The results demonstrated that SOX2 is overexpressed in BCC tissues and cells. In addition, SOX2 knockdown inhibited the migration and invasion of BCC cells, and the epithelial-mesenchymal transition (EMT) progress of BCC cells. It was also observed that SOX2 knockdown decreased SRPK1 expression, which further led to the downregulation of PI3K and AKT expression levels in BCC cells. Furthermore, SRPK1 transfection or PI3K/AKT pathway activation abolished the inhibitory effects of SOX2 knockdown on the migration, invasion and EMT progress of BCC cells. In conclusion, these results indicated that SOX2 may potentially serve as a target for BCC therapy by targeting the SRPK1-mediated PI3K/AKT signaling pathway.


[Primary hepatic actinomycosis: a case of inflammatory pseudotumor (case report)].
Actinomycosis is an uncommon chronic infection in which primary liver involvement accounts for 5% of all actinomycotic infections. Abdominal actinomycosis is a severe and progressive peritoneal infection due to an anaerobic gram-positive bacterium, Actinomyces israelii. The presence of a long-standing intrauterine device (IUD) is a well-known risk factor in young women. Although hepatic lesions are present in 15% of cases of abdominal actinomycotic infection, liver involvement in the majority of these cases is attributable to metastatic spread from other evident intraabdominal sites. Hepatic actinomycosis presents most commonly as a single abscess. However, hepatic actinomycosis can closely mimic a malignant tumor on clinical and radiological examination. Such lesions have been termed inflammatory pseudotumors. Tissue specimens for microscopic examination are necessary for diagnosis. We report a rare case of inflammatory pseudotumor of the liver caused by actinomycotic infection.


Potential Prospect of CDK4/6 Inhibitors in Triple-Negative Breast Cancer.
Triple-negative breast cancer (TNBC) is an aggressive, difficult-to-treat subtype of cancer with a poor prognosis; there is an urgent need for effective, targeted molecular therapies. The cyclin D/cyclin-dependent kinase (CDK)4/6-retinoblastoma protein (Rb) pathway plays a critical role in regulating cell cycle checkpoints, a process which is often disrupted in cancer cells. Selective CDK4/6 inhibitors can prevent retinoblastoma protein phosphorylation by invoking cell cycle arrest in the first growth phase (G1), and may therefore represent an effective treatment option. In this article, we review the molecular mechanisms and therapeutic efficacy of CDK4/6 inhibitors in combination with other targeted therapies for the treatment of triple-negative breast cancer. Three selective CDK4/6 inhibitors have so far received the approval of the Food and Drug Administration (FDA) for patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2) breast cancer. Trilaciclib, a small molecule short-acting inhibitor of CDK4/6, has also been approved recently for people with small cell lung cancer, and is also expected to be clinically effective against breast cancer. Although the efficacy of CDK4/6 inhibitors in patients with triple-negative breast cancer remains uncertain, their use in conjunction with other targeted therapies may improve outcomes and is therefore currently being explored. Identifying biomarkers for response or resistance to CDK4/6 inhibitor treatment may optimize the personalization of treatment strategies for this disease. Ongoing and future clinical trials and biomarker studies will shed further light on these topics, and help to realize the full potential of CDK4/6 inhibitor treatment in triple-negative breast cancer.


Protein crystallography using a multilayer monochromator.
A multilayer monochromator was installed on a bending-magnet beamline at the Cornell High Energy Synchrotron Source (CHESS) and was used to provide an unfocused pseudo-monochromatic X-ray beam for protein crystallography experiments. Datasets were collected from lysozyme at room temperature and human methylthioadenosine phosphorylase at 100 K. The wide energy bandpass of the multilayer allowed short exposure times, typically only a few times longer than on a focused multipole wiggler beamline. The diffraction images were processed using unmodified monochromatic data-processing software to yield datasets of good quality. These first measurements demonstrate that multilayer monochromators can be readily applied to the rapid structure determination of many typical-sized macromolecules.


Correlation between Glycated Hemoglobin and Triglyceride Level in Type 2 Diabetes Mellitus.
Dyslipidemia is quite prevalent in non-insulin dependent diabetes mellitus. Maintaining tight glycemic along with lipid control plays an essential role in preventing micro- and macro-vascular complications associated with diabetes. The main purpose of the study was to highlight the relationship between glycosylated hemoglobin (HbA1c) and triglyceride levels. This may in turn help in predicting the triglyceride status of type 2 diabetics and therefore identifying patients at increased risk from cardiovascular events. Hypertriglyceridemia is one of the common risk factors for coronary artery disease in type 2 diabetes mellitus (DM). Careful monitoring of the blood glucose level can be used to predict lipid status and can prevent most of the complications associated with the disease. This is a cross-sectional study using data collected from the outpatient diabetic clinic of Jinnah Postgraduate Medical Centre (JPMC) Karachi, Pakistan. Patients of age 18 years and above were recruited from the clinic. A total of consenting 509 patients of type 2 diabetes mellitus were enrolled over a period of 11 months. For statistical analysis, SPSS Statistics for Windows, Version 17.0 ( IBM Corp, Armonk, New York) was used and Chi-square and Pearson's correlation coefficient was used to find the association between triglyceride and HbA1c. The HbA1c was dichotomized into four groups on the basis of cut-off. Chi-square was used for association between HbA1c with various cut-off values and high triglyceride levels. Odds-ratio and its 95% confidence interval were calculated to estimate the level of risk between high triglyceride levels and HbA1c groups. The p-value < 0.05 was considered statistically significant for all the tests applied for significance. The association of high triglyceride was evaluated in four different groups of HbA1c, with a cut-off seven, eight, nine and 10 respectively. With HbA1c cut-off value of 7%, 74% patients had high triglycerides and showed a significant association with high triglyceride levels at p < 0.001 and odds ratio was 2.038 (95% confidence interval: 1.397 - 2.972). Logistic regression models were adjusted for demographic factors (age, race, gender), lifestyle factors (smoking, body mass index, lifestyle) and health status factors (blood pressure, physician-rated health status). After adjusting for relevant covariates, glycated hemoglobin was positively correlated with high triglyceride. Hence, HbA1c can be an indicator of triglyceride level and can be one of the predictors of cardiovascular risk factors in type 2 diabetes mellitus.


Use and discontinuation of hormone replacement therapy in women with myocardial infarction: a nationwide study.
General use of hormone replacement therapy (HRT) dropped drastically after 2002 when pivotal randomized trials showed increased risk of coronary artery disease and other complications with HRT. HRT is not recommended for primary or secondary prevention of coronary heart disease and guidelines recommend discontinuation of HRT after myocardial infarction (MI). It is unknown whether women actually discontinue HRT after MI. Women who use HRT when they experience their MI generally continue using HRT. We found a remarkably low increase in discontinuation after 2002, in contrast to the general drop in use of HRT. To characterize the pattern of use and discontinuation of postmenopausal hormone replacement therapy (HRT) in women with myocardial infarction (MI) before and after 2002, where the general use of HRT dropped drastically subsequent to the results of the Women's Health Initiative trial. All Danish women aged ≥40 years hospitalized with MI in the period 1997 to 2005 and their use of HRT were identified by individual-level-linkage of nationwide registers of hospitalization and drug dispensing from pharmacies. Characteristics associated with HRT use at time of MI and subsequent HRT discontinuation were analysed by multivariable logistic regression. In the study period, 34,778 women were discharged after MI. Of these, 3979 (11.4%) received HRT at the time of MI and their most used categories of HRT were vaginal oestrogen and oral oestrogen alone (46.6% and 28.7%, respectively). The percentage of women who continued HRT during the first year after discharge was 85.0% in the period 2000-2002 and had decreased to 79.6% in the period 2003-2005. Vaginal oestrogen use was associated with overall discontinuation of HRT (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.10, 1.72), whereas use of oral oestrogen alone and use of oral cyclic combined oestrogen/progestogen were associated with change of HRT after MI (OR 2.33, 95% CI 1.10, 4.93 and OR 2.94, 95% CI 1.35, 6.39, respectively). The majority of women experiencing an MI during ongoing HRT continued HRT after discharge and this pattern of HRT use did not change markedly after 2002.


Monte Carlo calculation of effective attenuation coefficients for various compensator materials.
Effective attenuation coefficients for 6, 8, and 15 MV photon beams were derived and studied for various compensator materials for square beams with side lengths of 0.5, 1.0, 2.0, 3.0, and 5.0 cm. Calculations were based on depth dose data in water obtained from EGS4 based DOSXYZ Monte Carlo simulations. Depth dose data were calculated using different compensator materials as attenuators of variable thickness. The absorbed dose varied exponentially as a function of absorber thickness at any depth in water on the beam axis for all materials. The effective attenuation coefficient data were compared with measurements for wax, aluminum and brass with values from the literature. Theoretical narrow beam linear attenuation coefficients were calculated and compared with the Monte Carlo data. The effective attenuation coefficient data for all materials were parametrized as functions of field size and depth in water. The effective attenuation coefficient was also parametrized as a function of atomic number. It was found that the effective attenuation coefficients calculated from the DOSXYZ data using a simple source model correspond to measured data for wax, aluminum and brass and published data for lead.


Anatomical and technical factors affecting the neural response to epidural spinal cord stimulation.
Spinal cord stimulation (SCS) is a common neurostimulation therapy to treat chronic pain. Computational models represent a valuable tool to study the potential mechanisms of action of SCS and to optimize the design and implementation of SCS technologies. However, it is imperative that these computational models include the appropriate level of detail to accurately predict the neural response to SCS and to correlate model predictions with clinical outcomes. Therefore, the goal of this study was to investigate several anatomic and technical factors that may affect model-based predictions of neural activation during thoracic SCS. We developed computational models that consisted of detailed finite element models of the lower thoracic spinal cord, surrounding tissues, and implanted SCS electrode arrays. We positioned multicompartment models of sensory axons within the spinal cord to calculate the activation threshold for each sensory axon. We then investigated how activation thresholds changed as a function of several anatomical variables (e.g. spine geometry, dorsal rootlet anatomy), stimulation type (i.e. voltage-controlled vs. current-controlled), electrode impedance, lead position, lead type, and electrical properties of surrounding tissues (e.g. dura conductivity, frequency-dependent conductivity). Several anatomic and modeling factors produced significant percent differences or errors in activation thresholds. Rostrocaudal positioning of the cathode with respect to the vertebrae had a large effect (up to 32%) on activation thresholds. Variability in electrode impedance produced significant changes in activation thresholds for voltage-controlled stimulation (38% to 51%), but had little effect on activation thresholds for current-controlled stimulation (less than 13%). Changing the dura conductivity also produced significant differences in activation thresholds. This study demonstrates several anatomic and technical factors that can affect the neural response to SCS. These factors should be considered in clinical implementation and in future computational modeling studies of thoracic SCS.


Halarchaeum rubridurum sp. nov., a moderately acidophilic haloarchaeon isolated from commercial sea salt samples.
Six halo-acidophilic archaeal strains were isolated from four commercial salt samples obtained from seawater in the Philippines, Indonesia (Bali) and Japan (Okinawa) on agar plates at pH 4.5. Cells of the six strains were pleomorphic, and stained Gram-negative. Two strains were pink-red pigmented, while four other strains were orange-pink pigmented. Strain MH1-16-3(T) was able to grow at 9-30% (w/v) NaCl [with optimum at 18% (w/v) NaCl], at pH 4.5-6.8 (optimum, pH 5.5) and at 20-50 °C (optimum, 42 °C). The five other strains grew at slightly different ranges. The six strains required at least 1 mM Mg(2+) for growth. The 16S rRNA gene sequences of the six strains were almost identical, sharing 99.9 (1-2 nt differences) to 100% similarity. The closest relatives were Halarchaeum acidiphilum MH1-52-1(T) and Halarchaeum salinum MH1-34-1(T) with 97.7% similarity. The DNA G+C contents of the six strains were 63.2-63.7 mol%. Levels of DNA-DNA relatedness amongst the six strains were 79-86%, while those between MH1-16-3(T) and H. acidiphilum MH1-52-1(T) and H. salinum MH1-34-1(T) were both 43 and 45% (reciprocally), respectively. Based on the phenotypic, genotypic and phylogenetic analyses, it is proposed that the six isolates represent a novel species of the genus Halarchaeum, for which the name Halarchaeum rubridurum sp. nov. is proposed. The type strain is MH1-16-3(T) ( =JCM 16108(T) =CECT 7535(T)).


Post-Translational Modifications of G Protein-Coupled Receptors Revealed by Proteomics and Structural Biology.
G protein-coupled receptors (GPCRs) are a protein superfamily comprising >800 members that regulate numerous cellular and physiologic responses. GPCRs represent the largest class of therapeutic targets with implications in various diseases. Although advances in GPCR structural and pharmacological research have significantly improved our knowledge of GPCR signaling mechanisms, mapping diverse post-translational modifications (PTMs) of GPCR proteins and understanding their regulatory roles have received much less attention. Mass spectrometry-based proteomics has become the most popular technology for profiling protein PTMs in a systematic manner. Herein we provide an overview of PTM types, locations, crosstalk and dynamic regulation for different GPCRs that are characterized using proteomic and/or biochemical approaches. Our main focus is on glycosylation, phosphorylation, ubiquitination and palmitoylation that are known to modulate receptor folding, biosynthesis, trafficking, dimerization and signaling. Furthermore, we discuss the locations of specific PTM sites in the structure of a given GPCR and its signaling complex to highlight the importance of PTM regulation in the molecular basis of GPCRs, which may shed new light on structure-based drug discovery.


Direct thrombin inhibition during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.
Patients with or at risk of heparin-induced thrombocytopenia (HIT) who are undergoing percutaneous coronary intervention (PCI) are at particular risk of thrombosis due to the prothrombotic nature of HIT and the endovascular disruption from PCI. Patients require aggressive anticoagulation during PCI, and alternative, nonheparin anticoagulation is recommended over heparin in patients with acute or previous HIT. Argatroban, bivalirudin, and lepirudin are nonheparin, fast-acting, parenteral direct thrombin inhibitors (DTIs). Multicenter, prospective studies have demonstrated that argatroban and lepirudin each reduce thrombosis in HIT and that argatroban and bivalirudin each provide adequate anticoagulation during PCI in patients with or at risk of HIT. We review current therapeutic practices with direct thrombin inhibitors in patients with or at risk of HIT during PCI, including individuals requiring periprocedural anticoagulation, and the factors influencing the choice of DTI in this setting.


Growth and liver histology of Channa punctatus exposed to a common biofertilizer.
Mustard oil cake (MOC) is widely used as biofertilizer in the field of agriculture and aquaculture. Channa punctatus was exposed to 0.42 g.L-1 sublethal concentration for 4, 7, 14, 21 and 28 days. Due to such exposure, body growth and histological changes in liver were observed. It was revealed that weight, length and breadth of fish were gradually increased with the days of exposure in compare to control fish, whereas, liver showed an increase in sinusoidal space and lipidosis during early days, followed by a recovery from the stress of MOC on the 28th day.


[Genotoxicity and lipid peroxidation caused by organic extracts of chlorinated drinking water in rats and HepG2 cells].
The genotoxic effects of chlorinated drinking water(CDW) extracts were examined in human HepG2 hepatoma cells, liver cells and polychromatic erythrocytes (PCEs) of bone marrow of Wistar rats by using in vivo and in vitro micronucleus(MN) test and single cell gel electrophoresis (comet assay). The influence of CDW on the lipidperoxidation (LPO) in blood and tissue of rats was also studied. The results indicated a significant increase of the frequencies of MN in PCEs at the low concentration of CDW and in HepG2 at the high concentration of CDW. The increased DNA breakage caused by CDW was observed in rat liver cells and in HepG2 cells by using comet assay. The levels of malon dialdehyde(MDA) were significantly increased almost in all animals and in all organs tested. A dose-dependent increases of MDA were observed in rat liver. It was demonstrated that CDW extracts caused genotoxic and oxidative damage on animals.


Budd-Chiari syndrome with inferior vena cava obstruction associated with systemic lupus erythematosus.
The Budd-Chiari syndrome is an uncommon condition in which hepatic venous outflow is obstructed by thrombosis of the major hepatic veins. Many of the cases are idiopathic, but it has been described in association with vena caval webs, abdominal trauma, retroperitoneal neoplasms, and hypercoagulable states. A patient with systemic lupus erythematosus (SLE) who developed the Budd-Chiari syndrome with inferior vena cava thrombosis led to a review of the possible association between SLE and the Budd-Chiari syndrome. The therapy of the Budd-Chiari syndrome with associated vena cava thrombosis is also discussed.


Calculated parenteral initial treatment of bacterial infections: Economic aspects of antibiotic treatment.
This is the seventeenth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. This chapter analyses economic aspects of antiinfective therapy. Any treatment decision is also a cost decision. In this chapter the authors particularly analyse whether or not there is evidence that certain clinically effective strategies as Antimicrobial Stewardship programs (AMS), guideline adherent initial therapy, early diagnostics, De-escalation, sequence therapy or therapeutic drug monitoring also have benficial economic effects. These can be direct savings or shortening of length of stay to free resources.


The effect of intranasally administered nitroglycerin on the blood pressure response to laryngoscopy and intubation in patients undergoing coronary artery by-pass surgery.
The effect of intranasally administered nitroglycerin (NTG) on the cardiovascular response to laryngoscopy and intubation was studied. Thirty patients scheduled to undergo coronary artery by-pass surgery under thiopentone, enflurane and pancuronium anaesthesia were randomly divided into three groups. Group I received lignocaine 1.5 mg/kg i.v. prior to laryngoscopy and intubation (control group). Group II received lignocaine 1.5 mg/kg i.v. and in addition 2 mg nitroglycerin (NTG) was given intranasally. Group III received only 2 mg NTG intranasally. In Group I laryngoscopy and intubation caused a significant increase in mean arterial pressure (MAP) (P less than 0.01), heart rate (HR) (P less than 0.01) and rate pressure product (RPP) (P less than 0.01) compared to preoxygenation values. In Group II and III MAP and RPP remained unchanged, whereas HR increased (P less than 0.01 and P less than 0.01 respectively). It can be concluded that intranasally administered NTG effectively attenuates the pressor response to laryngoscopy and intubation in patients presenting for coronary artery by-pass surgery and that it is more effective and convenient method than intravenous lignocaine.


Substrate curvature regulates cell migration.
Cell migration is essential in many aspects of biology. Many basic migration processes, including adhesion, membrane protrusion and tension, cytoskeletal polymerization, and contraction, have to act in concert to regulate cell migration. At the same time, substrate topography modulates these processes. In this work, we study how substrate curvature at micrometer scale regulates cell motility. We have developed a 3D mechanical model of single cell migration and simulated migration on curved substrates with different curvatures. The simulation results show that cell migration is more persistent on concave surfaces than on convex surfaces. We have further calculated analytically the cell shape and protrusion force for cells on curved substrates. We have shown that while cells spread out more on convex surfaces than on concave ones, the protrusion force magnitude in the direction of migration is larger on concave surfaces than on convex ones. These results offer a novel biomechanical explanation to substrate curvature regulation of cell migration: geometric constrains bias the direction of the protrusion force and facilitates persistent migration on concave surfaces.


Efficacy of S-1 for patients with peritoneal metastasis of gastric cancer.
This study was designed to examine the efficacy and compliance of S-1 for the patients with peritoneal metastasis of gastric cancer. Sixteen consecutive patients with peritoneal metastasis of gastric cancer were treated with S-1. Their survival was compared with that of the historical control group (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor were evaluated. The median survival time of S-1-treated patients was 550 days, which was significantly longer than that of the historical control group (215 days). We elucidated some factors to prolong the survival of the patients treated with S-1 for peritoneal metastasis: peritoneal metastasis without other distant metastases, the combination of S-1 treatment and gastrectomy, and low expression of thymidine phosphorylase mRNA in primary tumors. S-1 showed a surprisingly long-term survival with minimum toxicity in patients with peritoneal metastasis of gastric cancer.


Rosette-induced separation of T cells by acoustophoresis.
Breakthrough cell therapies for the treatment of cancers require the separation of specific cells, such as T cells, from the patient's blood. Current cell therapy processes rely on magnetic separation, which adds clinical risk and requires elevated manufacturing controls due to the added foreign material that constitutes the magnetic beads. Acoustophoresis, a method that uses ultrasound for cell separation, has demonstrated label-free enrichment of T cells from blood, but residual other lymphocytes limit the ultimate purity of the output T cell product. Here, to increase the specificity of acoustophoresis, we use affinity reagents to conjugate red blood cells with undesired white blood cells, resulting in a cell-cell complex (rosette) of increased acoustic mobility. We achieve up to 99% purity of T cells from blood products, comparable to current standards of magnetic separation, yet without the addition of separation particles.


[The surgery of open-angle glaucoma].
An overview of the necessary steps in making the surgical decisions in open angle glaucoma is presented. A surgical decision must consider the ocular hypertonia, the inefficacy of the medical treatment; the clinical stage of the ocular disease and general condition of the patient.


Erythrocyte Na+/Li+ countertransport and glomerular hyperfiltration in insulin-dependent diabetics.
Erythrocyte Na+/Li+ countertransport activity was investigated in 11 controls and 22 recent onset type I (insulin-dependent) diabetic patients with normal and high glomerular filtration rates. No differences in Vmax were observed in hyperfiltering compared to normofiltering patients or controls. The Na+/Li+ activity was correlated with blood glucose levels in insulin-dependent diabetics showing good glycemic control. Total cholesterol and triglyceride concentrations were similar among the three groups. In conclusion, enhanced Na+/Li+ countertransport activity is not associated, in our case, with diabetic condition per se and with early glomerular hyperfiltration and cannot be used as a marker of renal involvement in recent onset insulin-dependent diabetics.


A biochemical comparison of proteases from pathogenic naegleria fowleri and non-pathogenic Naegleria gruberi.
Naegleria fowleri is the etiologic agent of primary amoebic meningoencephalitis (PAM). Proteases have been suggested to be involved in tissue invasion and destruction during infection. We analyzed and compared the complete protease profiles of total crude extract and conditioned medium of both pathogenic N. fowleri and non-pathogenic Naegleria gruberi trophozoites. Using SDS-PAGE, we found differences in the number and molecular weight of proteolytic bands between the two strains. The proteases showed optimal activity at pH 7.0 and 35 degrees C for both strains. Inhibition assays showed that the main proteolytic activity in both strains is due to cysteine proteases although serine proteases were also detected. Both N. fowleri and N. gruberi have a variety of different protease activities at different pH levels and temperatures. These proteases may allow the amoebae to acquire nutrients from different sources, including those from the host. Although, the role of the amoebic proteases in the pathogenesis of PAM is not clearly defined, it seems that proteases and other molecules of the parasite as well as those from the host, could be participating in the damage to the human central nervous system.


Economic consequences of marital dissolution for blacks.
Paying particular attention to the economic impact of post-divorce on black survey respondents of both sexes, "this study analyzes Weitzman's suggestion that men and women lose economic well-being in the first year after divorce. Family incomes of divorced women and men are compared with [those of] their married counterparts for five SES [socioeconomic status] categories. Using t-tests, it was found that, for most categories, for both genders, incomes of divorced persons were lower than incomes of married persons. Family incomes were regressed against a set of four control variables and a marital status variable. The marital status variable was statistically significant for four of the five SES categories for females. This was not true for males. Policy implications are considered." The geographical focus is on the United States.


Bronchoscopist-Directed Continuous Flow Propofol Based Analgosedation during Flexible Interventional Bronchoscopy and EBUS.
Sedation techniques in interventional flexible bronchoscopy and endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) are inconsistent and the evidence for required general anesthesia under full anesthesiologic involvement is scarce. Moreover, we faced the challenge of providing bronchoscopic care with limited personnel. Hence, we retrospectively identified 513 patients that underwent flexible interventional bronchoscopy and/or EBUS-TBNA out of our institution between January 2020 and August 2022 to evaluate our deep analgosedation approach based on pethidine/meperidine bolus plus continuous flow adjusted propofol, the bronchoscopist-directed continuous flow propofol based analgosedation (BDcfP) in a two-personnel setting. Consequently, 502 out of 513 patients received BDcfP for analgosedation. We identified cardiovascular comorbidities, chronic obstructive pulmonary disease, and arterial hypertension as risk factors for periprocedural hypotension. Propofol flow rate did not correlate with hypotension. Theodrenaline and cafedrine might be used to treat periprocedural hypotension. Moreover, midazolam might be used to support the sedative effect. In conclusion, BDcfP is a safe and feasible sedative approach during interventional flexible bronchoscopy and EBUS-TBNA. In general, after the implementation of safety measures, EBUS-TBNA and interventional flexible bronchoscopy via BDcfP might safely be performed even with limited personnel.


Chiral separation of 12 pairs of enantiomers by capillary electrophoresis using heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin as the chiral selector and the elucidation of the chiral recognition mechanism by computational methods.
Chiral separation of 12 pairs of basic analyte enantiomers including oxybutynin, bambuterol, tradinterol, clenbuterol, clorprenaline, terbutaline, tulobuterol, citalopram, phencynonate, fexofenadine, salbutamol, and penehyclidine was conducted by capillary electrophoresis using a single-isomer anionic β-cyclodextrin derivative, heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin as the chiral selector. Parameters influencing separation were studied, including background electrolyte pH, heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin concentration, buffer concentration, and separation voltage. A background electrolyte consisting of 50 mM Tris-H3 PO4 and 6 mM heptakis-(2,3-diacetyl-6-sulfato)-β-cyclodextrin at pH 2.5 was found to be highly efficient for the separation of most enantiomers, with other conditions of normal polarity mode at 10 kV, detection wavelength of 210 nm using hydrodynamic injection for 3 s. Under the optimal conditions, baseline resolution (>1.50) for 11 pairs of enantiomers and somewhat lower resolution for penehyclidine enantiomers (1.17) were generated. Moreover, the possible mechanism of separation of clenbuterol, oxybutynin, salbutamol, and penehyclidine was investigated using a computational modeling method.


Propafenone: a new antiarrhythmic agent.
The chemical and pharmacologic properties, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, and dosage of propafenone are reviewed. Propafenone is a class IC antiarrhythmic agent that is structurally similar to the beta blockers but that has only weak beta-blocking and calcium-channel-blocking activity. It is well absorbed after oral administration, but systemic bioavailability is only 12% after a 300-mg dose. Among extensive metabolizers (greater than 90% of the United States population), bioavailability seems to vary nonlinearly with dose and increases substantially with food; these effects are not seen in poor metabolizers. Elimination is primarily hepatic, with a mean elimination half-life after oral administration of 5.5 hours in extensive metabolizers and 17.2 hours in poor metabolizers. The relationship between plasma propafenone concentration and clinical response varies considerably among individual patients; therefore, plasma concentrations have limited usefulness in predicting efficacy or electrophysiologic effects. Propafenone is effective in treating ventricular tachycardia and in suppressing premature ventricular complexes (PVCs). It is less effective in the treatment of refractory ventricular tachycardia. Concurrent administration of digoxin, warfarin, or metoprolol with propafenone has been shown to increase the serum concentrations of those three drugs, while cimetidine slightly increases the propafenone concentrations. Additive pharmacologic effect can occur when lidocaine, procainamide, and quinidine are combined with propafenone. Overall, 21% to 32% of patients experience adverse effects, with 3% to 7% of these serious enough to warrant discontinuing therapy. The most common adverse effects are dizziness or lightheadedness, metallic taste, and nausea and vomiting; the most serious adverse effects are proarrhythmic events.(ABSTRACT TRUNCATED AT 250 WORDS)


The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania.
1. Zonisamide, an anticonvulsant developed in Japan, is structurally similar to serotonin. Zonisamide has been proven to have a pharmacological profile that is very similar to that of carbamazepine. Thus, the effect of zonisamide was examined in 24 psychiatric patients: 15 with bipolar manic state, 6 with schizoaffective manic state, and 3 schizophrenic excitement. 2. Approximately 25% of all the patients and 33% of the bipolar manic patients showed remarkable global improvement with the addition of zonisamide. Approximately 71% of all the patients and 80% of the bipolar group had more than moderate global improvement. 3. No serious adverse reactions were found and no patients required zonisamide withdrawal. One patient developed both leukocytosis and mildly abnormal liver function test. One developed leukocytosis and another reported mild sleepiness. These reactions disappeared when zonisamide was discontinued.


E. coli chromosomal-driven expression of NADK2 from A. thaliana: A preferable alternative to plasmid-driven expression for challenging proteins.
The expression and purification of large recombinant proteins or protein complexes is problematic for some biotechnology laboratories. Indeed, it is often difficult to obtain enough active proteins to perform biological characterization or reach commercialization, when large proteins or protein complexes are expressed in E. coli via the popular T7-based plasmid-driven expression system. There is also an industrial demand to decrease our dependence on plasmid-driven expression, because of its drawbacks, such as: i) the common use of antibiotics to maintain the plasmid, ii) the issue of plasmid copy number, and iii) the risk of overloading the expression system. Despite all these issues, alternative solutions, such as gene integration in the bacterial chromosome, are rarely employed and their advantages are still a matter of debate. Plant plastidial NAD kinases (NADK; ATP:NAD 2'-phosphotransferase, EC 18.104.22.168) are a classic example of proteins with high molecular weight, that are difficult to express and purify with traditional T7-based technology. We therefore compared plasmid-driven and chromosomal-driven expression of the Arabidopsis thaliana NADK2 protein, using a proprietary counter-selection tool, COLIBELT®, that allows scar-free and marker-free chromosomal modifications. Here we show that chromosomal-driven expression allowed recovery of more active NADK2 protein than classic T7 expression systems, as well as better production, thus confirming that expression from one single chromosomal copy is preferable to plasmid-driven expression and might be appealing for both basic and applied research.


PTPRC (CD45) is not associated with multiple sclerosis in a large cohort of German patients.
Since contradictory results have been reported, we reanalysed the 77C-->G transition in exon 4 of the protein-tyrosine phosphatase receptor-type C (PTPRC also known as CD45) in a large cohort of German MS patients and controls. Different isoforms of the protein are expressed, depending on alternative splicing of exons 4 (CD45RA), 5 (CD45RB) and 6 (CD45RC) (CD45RO, exons 4-6 spliced out). The 77C-->G transition does not change the amino acid sequence, but it is probably part of a motif necessary for splicing leading to the isoform CD45RA. The expression of CD45RA is increased in 77C/G heterozygous individuals. The aim of the study was to clarify the importance of the PTPRC 77C-->G transition in our German cohort of MS patients. PCR products of exon 4 were digested using endonuclease MspI. The resulting restriction fragments of the wildtype C allele are 198 and 62 bp in length. In the G allele an additional restriction site is present yielding fragments of 114 and 84 bp. The G allele was identified in 10 of the 347 controls (1.4%) and in 7 of 454 MS patients (0.8%; Table 1). No homozygous individuals were found either in the control or in the patient group. Genetic association between the PTPRC 77C-->G transition and MS susceptibility was excluded in the MS cohort. In addition, subgrouping patients according to differences in the clinical course of MS or according to HLA-DRB1*15 status did not yield significant differences. The 77C-->G transition in exon 4 of the PTPRC gene may contribute to MS susceptibility only in very few families, if at all, but it is not relevant for the majority of MS cases, including virtually all German patients.


Trend analysis in the presence of short- and long-range correlations with application to regional warming.
Many real-world time series exhibit both significant short- and long-range temporal correlations. Such correlations enhance the errors of linear trend analysis. In this paper, we provide a general framework for trend analysis under the consideration of such correlations. We propose a parsimonious model containing both a single short-range autoregressive parameter and long-range fractional parameter. We derive analytical closed-form results for the error bars of the least-squares estimate of the trend for such time series, highlighting the different effects of short- and of long-range correlations. We employ an ensemble method for the automated extraction of scaling regions to estimate the fractional parameter of the data model together with its error bar, and the Grünwald-Letnikov derivative for the identification of the autoregressive parameter. We apply this framework to the study of warming trends on gridded temperature data in central Europe. We make use of the redundancy of the trend signal in adjacent grid points using methods of spatial averaging and the first principal component of empirical orthogonal function analysis. We find good agreement between the results of these two methods. We find a statistically significant decadal warming trend in central Europe over the past 70 years, which shows a particularly dramatic increase over the past 20 years.


Association of BRAF gene and TSHR with cervical lymph node metastasis of papillary thyroid microcarcinoma.
Differences in BRAF gene mutation frequency and thyroid-stimulating hormone receptor (TSHR) protein expression in thyroid tissues were detected to investigate their association with local tissue invasion and cervical lymph node metastasis potential of papillary thyroid microcarcinoma (PTMC). The BRAF gene mutation frequency and TSHR expression in PTMC patients were detected via qPCR and immunohistochemical method, and the association between them was discussed combined with the clinical and pathological parameters. Kruskal-Wallis test was used for the univariate correlation analyses and comparison of mutation rate and expression rate, and Chi-square test was used for the association of central lymph node metastasis with BRAF gene and TSHR. The BRAFV600E mutation only existed in patients with thyroid cancer. Τhe larger the number of metastatic central lymph nodes was, the higher the proportion of BRAFV600E mutation would be. Τhe BRAFV600E mutation was related to the primary lesion size, capsular infiltration and lymph node metastasis of PTMC (P<0.05). The expression of TSHR in PTMC tissues was < those in thyroid benign lesions and para-carcinoma normal tissues, which was positively associated with the central lymph node metastasis (P<0.05). Τhe low expression of TSHR was related to the primary lesion size, capsular infiltration and metastatic lymph nodes of PTMC (P<0.05). The BRAFV600E and TSHR may be involved in the occurrence and lymphatic metastasis of PTMC. The BRAFV600E mutation has no association with the TSHR protein expression (P=0.256), but the coincidence coefficient indicates that their diagnostic significance in PTMC is not similar, so BRAFV600E mutation and TSHR protein expression can be used jointly in the prediction of invasion and lymph node metastasis of PTMC, which may be more meaningful for clinical guidance.


Road crash fatality rates in France: a comparison of road user types, taking account of travel practices.
Travel practices are changing: bicycle and motorized two-wheeler (MTW) use are rising in some of France's large cities. These are cheaper modes of transport and therefore attractive at a time of economic crisis, but they also allow their users to avoid traffic congestion. At the same time, active transport modes such as walking and cycling are encouraged because they are beneficial to health and reduce pollution. It is therefore important to find out more about the road crash risks of the different modes of transport. To do this, we need to take account of the number of individuals who use each, and, even better, their travel levels. We estimated the exposure-based fatality rates for road traffic crashes in France, on the basis of the ratio between the number of fatalities and exposure to road accident risk. Fatality data were obtained from the French national police database of road traffic casualties in the period 2007-2008. Exposure data was estimated from the latest national household travel survey (ENTD) which was conducted from April 2007 to April 2008. Three quantities of travel were computed for each mode of transport: (1) the number of trips, (2) the distance traveled and (3) the time spent traveling. Annual fatality rates were assessed by road user type, age and sex. The overall annual fatality rates were 6.3 per 100 million trips, 5.8 per billion kilometers traveled and 0.20 per million hours spent traveling. The fatality rates differed according to road user type, age and sex. The risk of being killed was 20 to 32 times higher for motorized two-wheeler users than for car occupants. For cyclists, the risk of being killed, both on the basis of time spent traveling and the number of trips was about 1.5 times higher than for car occupants. Risk for pedestrians compared to car occupants was similar according to time spent traveling, lower according to the number of trips and higher according to the distance traveled. People from the 17-20 and 21-29 age groups and those aged 70 and over had the highest rates. Males had higher rates than females, by a factor of between 2 and 3. When exposure is taken into account, the risks for motorized two-wheeler users are extremely high compared to other types of road user. This disparity can be explained by the combination of speed and a lack of protection (except for helmets). The differential is so great that prevention measures could probably not eliminate it. The question that arises is as follows: with regard to public health, should not the use of MTW, or at least of motorcycles, be deterred? The difference between the fatality risk of cyclists and of car occupants is much smaller (1.5 times higher); besides, there is much room for improvements in cyclist safety, for instance by increasing the use of helmets and conspicuity equipment. Traffic calming could also benefit cyclists, pedestrians and perhaps moped users.


Cooperative effect of v-myc and v-erbA in the chick embryo.
We show that a construct designated as MAHEVA, which encodes oncogenes v-myc from MH2 virus and v-erbA from AEV under the control of the LTR of MH2, induces rapidly growing heart rhabdomyosarcomas, when it is injected in E3 but not E5 chick embryos. A similar pathology has previously been observed with MC29, within the same limited time frame. The tumors, which expressed P61-63myc, P75gag-erbA and Pr76gag proteins were detectable from E14 onwards. Compared with MC29, MAHEVA induced a secondary anomaly, not detectable prior to E17. This is the appearance of cartilage nodules within the heart rhabdomyosarcomas. The constant location of these nodules inside the rhabdomyosarcomas and their delayed appearance suggests that the chondrocytes originate from myoblasts prevented from differentiating by the expression of the v-myc product. This interpretation is supported by the appearance of chondrocytes in E3 heart muscle cells infected in vitro with MAHEVA.


[Effects of wild-type PTEN overexpression and its mutation on F-actin in activated hepatic stellate cells].
Objective: To investigate the effect of overexpression of wild-type phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and its mutant G129E (exhibiting the activity of protein phosphatase and losing the activity of lipid phosphatase) on F-actin in activated hepatic stellate cells (HSCs) cultured in vitro. Methods: The activated hepatic stellate cell-T6 (HSC-T6) cells were cultured in vitro, and activated HSCs were transfected with adenovirus that carried wild-type PTEN gene and G129E gene using transient transfection. The HSCs were divided into the following groups: control group, which was transfected with DMEM medium instead of virus solution; Ad-GFP group, which was transfected with the empty adenovirus vector with the expression of green fluorescent protein (GFP); Ad-PTEN group, which was transfected with the recombinant adenovirus with wild-type PTEN gene and GFP expression; Ad-G129E group, which was transfected with the recombinant adenovirus with G129E gene and GFP expression. Western blot and quantitative real-time PCR were used to measure the protein and mRNA expression of PTEN in activated HSCs; under a laser scanning confocal microscope (LSCM), phalloidine labeled with the fluorescein tetramethylrhodamine isothiocyanate (TRITC) was used to observe the morphology of HSCs, distribution and fluorescence intensity of F-actin, and changes in pseudopodia and stress fibers, and a calcium fluorescence probe (Rhod-2/AM) was used to measure the changes in Ca(2+) concentration in HSCs. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference test was used for comparison between two groups. Results: Wild-type PTEN and G129E genes were highly expressed in activated HSCs. In the control group and the Ad-GFP group, HSCs had a starlike or polygonal shape, F-actin was reconfigured and formed a large number of stress fibers which stretched across the whole cell, and layered pseudopodia were seen around the cell. In the Ad-PTEN group and the Ad-G129E group, the HSCs had a fusiform shape, F-actin was mainly seen around the cell, a small number of stress fibers were seen inside the cell, and layered pseudopodia around the cell disappeared. The Ad-PTEN group and the Ad-G129E group had significant reductions in the fluorescence intensity of F-actin compared with the control group and the Ad-GFP group (357.67±13.39/377.25±14.55 vs 961.87±27.33/954.68±20.71, F = 1783.486, P < 0.05), while there were no significant differences between the Ad-PTEN group and the Ad-G129E group, as well as between the control group and the Ad-GFP group (P > 0.05). The Ad-PTEN group and the Ad-G129E group had significant reductions in the relative concentration of Ca(2+) compared with the control group and the Ad-GFP group (251.60±90.88/352.18±146.01 vs 1953.95±132.99/1937.57±115.17, F = 834.988, P < 0.05), while there were no significant differences between the Ad-PTEN group and the Ad-G129E group, as well as between the control group and the Ad-GFP group (P > 0.05). Conclusion: The overexpressed wild-type PTEN and its mutant G129E can significantly inhibit the formation and reconfiguration of cytoskeletal protein F-actin and reduce the concentration of Ca2+ in activated HSCs in vitro. In addition, there are no significant differences in the above effects between wild-type PTEN and G129E.


Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement.
This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired dissipation of electric currents. Here, we applied the hexagonal arrangement to the microelectrode array for the localized activation of retinal cells and better visual acuity. To provide stimuli more efficiently to non-spiking neurons, a 3D structure was created through a customized pressing process, utilizing the elastic property of the materials used in the fabrication processes. The diameter and pitch of the Pt-coated electrodes were 150 μm and 350 μm, respectively, and the height of the protruded electrodes was around 20 μm. The array consisted of 98 hexagonally arranged electrodes, supported by a flexible and transparent polydimethylsiloxane (PDMS) base, with a thickness of 140 μm. Also, the array was coated with 2 μm-thick parylene-C, except the active electrode sites, for more focused stimulation. Finally, the electrochemical properties of the fabricated microelectrodes were characterized, resulting in the mean impedance of 384.87 kΩ at 1 kHz and the charge storage capacity (CSC) of 2.83 mC·cm-2. The fabricated microelectrodes are to be combined with an integrated circuit (IC) for additional in vitro and in vivo experiments.


A mutant form of MeCP2 protein associated with human Rett syndrome cannot be displaced from methylated DNA by notch in Xenopus embryos.
MeCP2 is a DNA binding protein that represses transcription of methylated genes in vitro, but the endogenous function of MeCP2 in vivo is unclear. Here, we demonstrate that in Xenopus laevis embryos MeCP2 is a partner of the SMRT corepressor complex that regulates the expression of a neuronal repressor xHairy2a in differentiating neuroectoderm. The MeCP2/SMRT complex is bound to the promoter of the silenced xHairy2a gene and is displaced upon activation by the Notch intracellular domain (NICD). A truncated form of MeCP2 (R168X) found in patients with Rett syndrome cannot interact with the SMRT complex or fully activate xHairy2a during primary neurogenesis. This disruption of MeCP2 activity results in abnormal patterning of primary neurons during neuronal differentiation. Our results support a model whereby the dynamic association of MeCP2 with methylated DNA and the SMRT complex regulates a gene involved in cell fate decisions during primary neurogenesis in Xenopus.


A positron emission tomography study on the role of nigral lesions in parkinsonism in patients with amyotrophic lateral sclerosis.
Patients with amyotrophic lateral sclerosis (ALS) sometimes exhibit parkinsonism, but the lesion responsible for parkinsonism has not been extensively studied. To test whether nigrostriatal system dysfunction is responsible for parkinsonism in ALS. From the 182 ALS patients who were admitted to our neurology ward during the past 10 years, we extracted all the patients who satisfied the criteria of both parkinsonism and ALS. The University of Tokyo Hospital. We conducted [(18)F]L-dopa and [(11)C]N-methylspiperone positron emission tomography and technetium Tc 99m hexamethylpropyleneamine oxime single-photon emission computed tomography studies on 5 patients with ALS manifesting overt parkinsonism. Two male and 3 female patients (average age, 63.2 +/- 5.8 years) had ALS for an average of 28.6 +/- 21.5 months and had parkinsonism for an average of 15.2 +/- 11.4 months. Features of their parkinsonism were characterized by outstanding bradykinesia without resting tremor or dementia. The results of positron emission tomography studies indicated normal nigrostriatal function, but those of single-photon emission computed tomography demonstrated decreased blood flow in the frontotemporal cortices. It is likely that parkinsonism in ALS is due to cortical lesions rather than nigrostriatal dysfunction and that both symptoms are the clinical manifestation of frontotemporal dementia with motor neuron diseases, including classic ALS.


An optimized strategy for ICAT quantification of membrane proteins.
The work presented here focuses on the development of a method adapting isotope labeling of proteins with ICAT to the study of highly hydrophobic proteins. Conditions for the labeling of proteins were first established using two standard soluble proteins and iodoacetamidyl-3,6-dioxaoctanediamine biotin (PEO-iodoacetyl biotin). Results demonstrated the efficiency of the labeling in the presence of high concentrations of both SDS and urea. These conditions were then used to label a highly hydrophobic mitochondrial membrane protein, the adenine nucleotide translocator ANT-1, with PEO-iodoacetyl biotin and then with the cleavable ICAT reagent. The results presented here show that labeling of proteins with cleavable ICAT is possible and may even be improved in strong denaturing buffers containing both SDS at a concentration higher than 0.5% (w/v) and urea. These results open the possibility of applying the ICAT strategy to complex samples containing very hydrophobic proteins solubilized in urea-SDS buffers. The adaptability of the developed method is demonstrated here with preliminary results obtained during the study of membrane-enriched fractions prepared from murine embryonic stem cells.


Diagnostic pitfalls and accuracy of diagnosis in acute abdominal pain.
To identify the differential diagnostic difficulties in acute abdominal pain at the emergency department and during hospitalization. Patients with abdominal pain lasting for up to 7 days were registered during 1997-2000 and re-evaluated one year after discharge (n=2851). Diagnoses with low sensitivity at the emergency department but markedly increased sensitivity at discharge were non-specific abdominal pain with a sensitivity value at the emergency department of 0.43, appendicitis 0.80, gallstones 0.68, constipation 0.74 and peptic ulcer 0.26. Corresponding kappa-values were 0.48, 0.74, 0.84, 0.88 and 0.93, respectively. Malignancy, gynaecological complaints, dyspepsia, urinary tract infection and diverticulitis displayed fairly good concordance between the preliminary and discharge judgements, but the predictive diagnostic value was still low at discharge. Sensitivity values at discharge were 0.40, 0.75, 0.73, 0.77 and 0.83, respectively. Among 479 surgically treated patients, 104 initially received a diagnosis usually not requiring surgery and had a median delay until operation of 22 h (95% CI 30-50 h), compared with 8 h (12-18 h) for referrals. Non-specific abdominal pain is the main differential diagnostic problem in the emergency department also for diagnoses requiring surgery. Constipation is a diagnostic pitfall and when making this diagnosis a careful re-evaluation is necessary.


Tramadol and beta-cyclodextrin piroxicam: effective multimodal balanced analgesia for the intra- and postoperative period.
This study was conducted to evaluate the analgesic efficacy of tramadol, an analgesic with both opioid and nonopioid actions (norepinephrine and serotonin pathways), with beta-cyclodextrin piroxicam, a nonsteroidal antiinflammatory drug, in the perioperative setting. The study population consisted of 48 patients scheduled for minor abdominal procedures, who were assigned to one of four groups of 12 patients each. The premedication was either a placebo tablet or a 192.1-mg beta-cyclodextrin piroxicam tablet, administered orally 30-40 minutes before anesthesia induction. After intravenous administration of tramadol 1.5 mg/kg, anesthesia was induced with an intravenous loading dose of propofol. Anesthesia was maintained an intravenous infusion of propofol at 6-12 mg/kg/h plus either saline or tramadol at 1.2 mg/kg/h, atracurium, and a 2:1 nitrous oxide-oxygen mixture. The control group received a placebo tablet and an infusion of saline with propofol for anesthesia maintenance; the tramadol group received a placebo tablet and a continuous tramadol-propofol infusion; the beta-cyclodextrin piroxicam (BCP) group received a BCP tablet and a continuous saline-propofol infusion; and the beta-cyclodextrin piroxicam-tramadol (BCPT) group received beta-cyclodextrin piroxicam and a continuous tramadol-propofol infusion. The relative propofol consumption by the four groups was control = BCP (P > .05) >tramadol (P < .001) > B-CPT (P < .0002). The time for analgesic rescue decreased in the order BCPT > BCP (P < .0002) = tramadol > control (P < .001). The degree of sedation and the visual analog scores 10-cm scale at the time patients requested rescue analgesics were similar among the groups (P > .05). The combination of tramadol and beta-cyclodextrin piroxicam provided better perioperative analgesia than tramadol alone.


Pelvic radiograph in skeletal dysplasias: An approach.
The bony pelvis is constituted by the ilium, ischium, pubis, and sacrum. The pelvic radiograph is an important component of the skeletal survey performed in suspected skeletal dysplasia. Most of the common skeletal dysplasias have either minor or major radiological abnormalities; hence, knowledge of the normal radiological appearance of bony pelvis is vital for recognizing the early signs of various skeletal dysplasias. This article discusses many common and some uncommon radiological findings on pelvic radiographs along with the specific dysplasia in which they are seen; common differential diagnostic considerations are also discussed.


In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues.
GnRH analogues are effective targeting moieties and able to deliver anticancer agents selectively into malignant tumor cells which highly express GnRH receptors. However, the quantitative analysis of GnRH analogues' cellular uptake and the investigated cell types in GnRH-based drug delivery systems are currently limited. Previously introduced, selectively labeled fluorescent GnRH I, -II and -III derivatives provide great detectability, and they have suitable chemical properties for reproducible and robust experiments. We also found that the appropriate up-to-date methods with these labeled GnRH analogues could offer novel information about the GnRH-based drug delivery systems. This manuscript introduces some simple and fast experiments regarding the cellular uptake of [D-Lys6(FITC)]-GnRH-I, [D-Lys6(FITC)]-GnRH-II and [Lys8(FITC)]-GnRH-III on the EBC-1 (lung), the BxPC-3 (pancreas) and on the Detroit-562- (pharynx) malignant tumor cells. In parallel with these GnRH-FITC conjugates, the cell surface level of GnRH-I receptors was also examined on these cell lines before and after the GnRH treatment by confocal laser scanning microscopy. The cellular uptake of GnRH-FITC conjugates was quantified by fluorescence-activated cell sorting. In these experiments minor differences among GnRH analogues and major differences among cell types was observed. The significant differences among cell lines are correlated with their distinct level of cell surface GnRH-I receptors. The introduced experiments contain practical methods to visualize, quantify and compare the uptake efficiency of GnRH-FITC conjugates in a time- and concentration-dependent manner on various adherent cell cultures. These results could predict the drug targeting efficiency of GnRH conjugates on the given cell culture, and offer a good basis for further experiments in the examination of GnRH-based drug delivery systems.


Protracted febrile myalgia syndrome in a Japanese patient with fasciitis detected on MRI.
Protracted febrile myalgia syndrome (PFMS) is a rare manifestation of familial Mediterranean fever characterized by prolonged severe myalgia. We herein describe a case of PFMS with fasciitis on magnetic resonance imaging. The response to corticosteroid therapy was prompt, as is typical for PFMS. An MEFV gene analysis revealed the patient to be homozygous for E148Q and compound heterozygous for P369S-R408Q. This is the first case report of a Japanese patient with PFMS. MRI findings may help to diagnose such cases.


Accuracy of Capillary Hemoglobin Measurements for the Detection of Anemia among U.S. Low-Income Toddlers and Pregnant Women.
The aim of this study is to evaluate the accuracy of capillary hemoglobin (Hb) measurements in detecting anemia among low-income toddlers (aged 12-35 months) and pregnant women. In analyses of data among toddlers from Kansas City (n = 402) and St. Louis, Missouri (n = 236), and pregnant women at <20 weeks gestation from Cleveland, Ohio (n = 397), we compared subjects' anemia status based on capillary Hb concentrations in finger puncture samples as measured by the HemoCue system with their anemia status based on venous Hb concentrations as measured by the HemoCue and Coulter Counter. The sensitivity of capillary blood analyses in identifying cases of anemia was 32.8% (95% Confidence Intervals (CI): 21.0%-46.3%), among Kansas City toddlers, 59.7% (95% CI: 45.8%-72.4%) among St. Louis toddlers, and 66.7% (95% CI: 46.0%-83.5%) among pregnant women in Cleveland; the corresponding specificities were 97.7%, 86.6%, and 96.7%, respectively. The correlation between HemoCue and Coulter Counter measurements of venous Hb (0.9) was higher than that between HemoCue measurements of capillary and venous blood (0.8). The results show that Hb measurements of capillary blood with HemoCue were not optimal for determining the anemia status of toddlers and pregnant women.


Guidelines for staff administering laser therapy in an office setting.
Advances in laser technology provide not only new opportunities, but an increase in laser applications. Many independent clinics now offer laser treatments. Use of laser treatment and related services should only be provided to patients by appropriately trained and qualified personnel. This article outlines the roles and responsibilities of the healthcare team working in independent laser healthcare facilities. The article is meant to assist clinics in developing their own quality management programs and is intended only to act as a guide to ensure that treatment is provided by qualified professionals in the safest, most effective manner. Staff working in laser clinics are responsible for the operation of lasers during treatment. They are also responsible for patient and staff safety, implementation of standards of care, and providing only procedures that meet and follow strict safety parameters. Accidents will occur with lasers when providers do not have the proper skills, training, and education on laser treatments. Regardless of many safety regulations involving laser use, little is written on the qualifications, selection, and ongoing education of the professional and technical staff working in independent healthcare facilities offering laser services. This article provides a detailed outline of the necessary skills and knowledge the nurses and the support staff need to possess to use lasers for patient treatment in laser treatment centers. Staff educated in laser science and safety can recognize potential hazards and ensure that safety standards are actively integrated into the daily practice of patient care.


Assessing the risk of vertebral osteoporosis.
Assessment of osteoporosis includes an accurate diagnosis, a consideration of the differential diagnosis, and prognostic assessment. Diagnosis of osteoporosis is based on bone mineral density (BMD) measurements and is defined as a BMD value that is 2.5 standard deviations or more below the average value in young healthy women (T score < or = -2.5 SD). Established osteoporosis is defined as a T-score of < or = -2.5 SD in the presence of a prior fragility fracture. The assessment of prognosis is important for defining intervention thresholds. Future fracture risk depends not only on BMD, but also on age. In addition, a variety of risk factors have been identified that increase fracture risk over and above that provided by BMD and age. Of particular importance is a prior fragility fracture, low body mass index and use of corticosteroids. The combination of independent risk factors permits a more accurate stratification of risk so that more patients at high risk can be identified. Risk of future fracture is optimally expressed as a probability. Ten-year fracture probabilities are appropriate for clinical use. The impact of BMD, age and other risks on fracture probability have recently been determined and provide a mechanism for optimising assessment of patients so that treatments can be efficiently directed to those most in need.


Applications of indocyanine green (ICG) fluorescence technology in open surgery: preliminary experience in pediatric surgery.
Indocyanine green fluorescence technology (ICG) in pediatric minimally invasive surgery has undergone an important improvement in the last 5 years. However, its use in open surgery is still limited. In this paper, we aim to report our preliminary experience with Rubina® lens ICG fluorescence technology in combination with the IMAGE1 S™ system from KARL STORZ in open excision of masses in children. The records of 18 patients undergoing open surgery for head, neck and thorax masses between September and November 2022 were retrospectively reviewed. Rubina® lens ICG fluorescence technology system was used in all the cases. In 10 cases we adopted the holding arm system and in 8 cases the hand-held technique. Data about patients' demographics, surgery and outcomes were collected and analyzed through the following criteria: mass localization, intraoperative time (min), ICG administration (ml), intraoperative complications, postoperative complications. A total of 18 patients were operated: 4 thyroglossal duct cysts, 3 supraorbital cysts, 2 neck masses, 2 pre-auricular and 2 scalp cysts, 2 gynecomastias, 2 lymphangiomas, 1 nose mass. In all the cases, intralesional injection of 0.5-1 ml of ICG solution was performed peri-operatively. Mean operative time was 58.4 min (35-134 min). Postoperative complications included seroma formation in 2 cases. Surgical pathology reports confirmed complete mass excision in all the cases. Based on our preliminary experience, ICG fluorescence guided surgery using Rubina® lens system was very helpful also in open surgery procedures. Rubina® lens system permits to have a very low complication rate, a time-saving surgery, a real time reliability of anatomic structures and an excellent clinical safety. In our experience, holding arm system seems more comfortable than hand-held system. However, further cases need to be performed to evaluate the exact role and to identify new indications of this technique in open pediatric surgical procedures.


Stroke and migraine.
Young patients with migraine are at increased risk for stroke, particularly patients with an aura of focal neurologic deficits. Other causes of ischemia are often identified in patients with migraine, including patent foramen ovale, lupus anticoagulant, cervical carotid dissection, arteriovenous malformation, and hyperactivity of the clotting system. Migrainous stroke is only diagnosed when all other possible causes of stroke have been eliminated and the patient has irreversibility of the usual aura, associated with an ischemic infarct in the appropriate brain territory. Prophylactic therapy of migraine with aura may be beneficial in preventing migrainous stroke.


The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke.
To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. A JBA was defined as an area of pixels with a grayscale value <25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA <4 mm(2), 1.4% in 171 patients with a JBA 4 to 8 mm(2), 3.2% in 46 patients with a JBA 8 to 10 mm(2), and 5% in 198 patients with a JBA >10 mm(2) (P < .001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (<4 mm(2), 4-8 mm(2), >8 mm(2)) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was <1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation.


The effect of digital dermatitis on hoof conformation.
Digital dermatitis (DD) is the most prevalent cause of lameness of infectious origin in cattle. However, little is known about the effects of DD on hoof conformation (HC) during the clinical disease. The objectives of the present study were to (1) evaluate the changes in HC observed in feet affected with clinical DD lesions and (2) investigate the temporal relationship between DD and heel horn erosion (HHE). A longitudinal study was carried out including a cohort of 644 Holstein heifers. Digital dermatitis, HC, and presence of HHE in the rear feet of each heifer were assessed during a period of 6 mo. A total of 1,979 feet evaluations were included in the data set, of which 157 corresponded to feet presenting DD lesions >20mm [mean (SD) size of 27.2 (8.2) mm]. Age, days of pregnancy, hip height, and girth circumference were also recorded at cow level. Significant HC changes were observed in DD-affected feet. Results standardized to a period of 90d of follow-up showed an increase in heel height [mean (95% CI) 3.4 (2.5, 4.4) and 2.8 (2.0, 3.7) mm] and claw angle [0.8 (0.2, 1.4) and 1.4 (0.7, 2.0) degrees] of the medial and lateral claws, respectively. In addition, an increase in depth of the interdigital cleft [3.2 (2.7, 3.7) mm] and on debris accumulation [14% (7, 21) of feet] was also observed. Feet affected with clinical DD lesions also experienced a 46% point increase in the presence of severe HHE. In the short term, HC changes returned to normal levels when clinical cure of DD was achieved after topical treatment. In conclusion, significant HC changes occur in heifers affected by clinical DD before lameness symptoms are detected. The transformation of the heel area in feet affected by DD likely promotes the creation of a local environment that favors the persistence of the disease and the occurrence of severe HHE. To avoid further hoof damage, active surveillance and early intervention to reduce HC changes are recommended to improve DD control programs. Successful restoration of HC can be achieved upon clinical cure of DD. The long-term effects in lifetime performance of the HC changes due to DD remain to be further investigated.


[Isolation of Yersinia enterocolitica in acute ileitis].
2246 stool specimens were specifically testet for Yersinia enterocolitica during 1973/74. In one case it was possible to isolate a strain of Yersinia enterocolitica (0-group I of Knapp/Serotype 3 of Winblad) from the feces of a patient suffering of acute ileitis. A high agglutinine-titer was serologically detected against a bacterial suspension of the isolated strain as well as of a reference strain (Serotype 3 of Winblad). The antibody-titer was 1 : 3200 by the first examination and dropped to 1 : 160 after two months. A reisolation attempt was unsuccessful.


Integrative Analysis of DNA Methylation and Gene Expression Identified Follicular Thyroid Cancer-Specific Diagnostic Biomarkers.
The diagnosis of follicular thyroid carcinoma (FTC) prior surgical resection remains a challenge, as routine screening methods, such as ultrasound or even FNAB, could not diagnose FTC preoperatively. Here, we performed an integrative analysis of DNA methylation and RNA array data from our own cohort (14 Follicular thyroid carcinoma vs 16 Benign thyroid lesion) to identify thyroid cancer-specific DNA methylation markers. We first identified differentially methylated and expressed genes and examined their correlations. Candidate DNA methylation sites were selected and further verified in validation set. Among all candidate methylation sites, cg06928209 was the most promising site as a molecular marker for early diagnosis, with a sensitivity of 90%, a specificity of 80% and an AUC of 0.77. Overall, our study demonstrates the potential use of methylation markers in FTC diagnosis and may boost the development of new epigenetic therapies.


Half-sandwich (η5-Cp*)Rh(iii) complexes of pyrazolated organo-sulfur/selenium/tellurium ligands: efficient catalysts for base/solvent free C-N coupling of chloroarenes under aerobic conditions.
Three new pyrazolated chalcogenoether ligated Rh(iii) half-sandwich complexes (1-3) were synthesised by the thermal reaction of chalcogenoether (S, Se and Te) substituted 1H-pyrazole ligands (L1-L3) and [(η5-C5Me5)RhCl]2 in methanol. The complexes were fully characterised by various spectroscopic techniques, and the molecular structures of complexes 1 and2 were also established through single crystal X-ray crystallographic analysis, which indicates a pseudo-octahedral half-sandwich piano-stool geometry around the rhodium metal. All three complexes were found to be thermally stable and insensitive towards air and moisture. One mol% of Rh(iii) complexes (1-3) along with 10 mol% of Cu(OAc)2 were explored for the Buchwald-Hartwig type C-N coupling reactions of amine and aryl chloride. Good to excellent yields (89-92%) of the coupling products were obtained with seleno- and thio-ether functionalised pyrazolated Rh(iii) complexes (1 and 2), while an average yield (39%) was obtained with the telluro-ether functionalised complex (3). In contrast to the previously reported C-N coupling reactions the present reaction works under solvent- and base-free conditions, and the coupling reaction is accomplished in just 6 h with a high yield of the coupling product. The present methodology was also found to be efficient for a wide variety of functionalised aryl halides, and aliphatic or aromatic amines (1° and 2°). Moreover, the reaction also enables the C-N coupling of electron-withdrawing substrates and base-sensitive functionalities.


2,5-Bis[4-(dimethyl-amino)-phen-yl]-3,6-dimethyl-pyrazine.
The title compound, C(22)H(26)N(4), was prepared from p-dimethyl-amino-propiophenone in six steps. The mol-ecule has no crystallographic symmetry. The dihedral angles between the pyrazine ring and the phenyl rings are 35.81 (6) and 37.11 (8)°. The dimethyl-amino groups are essentially planar (sum of the bond angles at N = 359.3 and 359.9°) and nearly coplanar with the adjacent aromatic ring [dihedral angles = 5.54 (11) and 7.40 (3)°]. This effect and the short aniline C-N bonds can be rationalised in terms of charge transfer from the amino groups to the central pyrazine ring.


A stable physisorbed layer of packed capture antibodies for high-performance sensing applications.
Antibody physisorption at a solid interface is a very interesting phenomenon that has important effects on applications such as the development of novel biomaterials and the rational design and fabrication of high-performance biosensors. The strategy selected to immobilize biorecognition elements can determine the performance level of a device and one of the simplest approaches is physical adsorption, which is cost-effective, fast, and compatible with printing techniques as well as with green-chemistry processes. Despite its huge advantages, physisorption is very seldom adopted, as there is an ingrained belief that it does not lead to high performance because of its lack of uniformity and long-term stability, which, however, have never been systematically investigated, particularly for bilayers of capture antibodies. Herein, the homogeneity and stability of an antibody layer against SARS-CoV-2-Spike1 (S1) protein physisorbed onto a gold surface have been investigated by means of multi-parametric surface plasmon resonance (MP-SPR). A surface coverage density of capture antibodies as high as (1.50 ± 0.06) × 1012 molecules per cm-2 is measured, corresponding to a thickness of 12 ± 1 nm. This value is compatible with a single monolayer of homogeneously deposited antibodies. The effect of the ionic strength (is) of the antibody solution in controlling physisorption of the protein was thoroughly investigated, demonstrating an enhancement in surface coverage at lower ionic strength. An atomic force microscopy (AFM) investigation shows a globular structure attributed to is-related aggregations of antibodies. The long-term stability over two weeks of the physisorbed proteins was also assessed. High-performance sensing was proven by evaluating figures of merit, such as the limit of detection (2 nM) and the selectivity ratio between a negative control and the sensing experiment (0.04), which is the best reported performance for an SPR S1 protein assay. These figures of merit outmatch those measured with more sophisticated biofunctionalization procedures involving chemical bonding of the capture antibodies to the gold surface. The present study opens up interesting new pathways toward the achievement of a cost-effective and scalable biofunctionalization protocol, which could guarantee the prolonged stability of the biolayer and easy handling of the biosensing system.


Observation of a discrete family of dissipative solitons in a nonlinear optical system.
We report on the observation of a discrete family of spatial dissipative solitons in a simple optical pattern forming system, which is based on a modified single-mirror feedback arrangement. After a pitchfork bifurcation the system possesses two (nearly) equivalent coexisting states of different polarizations. The spatial solitons correspond to excursions from one of the two states serving as a background state towards the other one. The members of the soliton family differ in the number of high-amplitude radial oscillations. The observations are in good agreement with numerical simulations and general expectations for dissipative solitons.


Clinical characteristics of patients with mpox infection in the United Arab Emirates: a prospective cohort study.
The study aims to explore the risk factors, clinical characteristics, and outcomes of mpox infection in Abu Dhabi, United Arab Emirates (UAE). A prospective cohort study was conducted at two communicable disease centers in Abu Dhabi, UAE and patients admitted with confirmed mpox infections between May 01, 2022 and December 31, 2022 were included in our study. A total of 176 mpox patients were admitted, of which 93% (n = 164) were men and mean age was 30.4 ± 7 years. Individuals presented with mucocutaneous lesions, most commonly on the genital and anal regions (n = 157; 89%). Only 70 (39.8%) gave a history of sexual exposure. The most common systemic symptoms reported were fever (n = 91; 52%), exanthema (n = 92; 52%), and inguinal lymphadenopathy (n = 60; 34%). Median timeframe from systemic symptoms to appearance of lesions was 4 days (interquartile range 4-6 days). Complications were observed in seven (4%) participants; two (1.1%) individuals developed conjunctivitis, four (2.3%) patients developed penile edema, and one (0.6%) case of myocarditis was reported. In 60% (n = 106) of patients, a potential source of sexual exposure was not identified. The clinical characteristics of mpox cases in the UAE are similar to those in other countries. However, cultural and religious factors likely prevent patient disclosure of sexual exposure and symptoms, contributing to the limited information about the disease in the Middle East.


[Swimming training enhances muscle growth and potentiates p70s6k, rpS6 protein expression in rat skeletal muscle].
To illustrate the molecular mechanism of skeletal muscle growth by examining the effect of swimming training on skeletal muscle growth and p70s6k, rpS6 protein expression. Twenty four male SD rats were used to establish swimming training models with a 15% body mass load. The training protocol adopted interval swimming training (every other day with 8 weeks). The gastrocnemius and soleus muscle were collected and weighed after training, and the protein expression of p70s6k, rpS6 and their phosphorylated forms were examined. After 8 weeks treatment, no significant change was observed in skeletal muscle mass between training group (T) and control group (C) (P > 0.05), but muscle mass in training rapamycin (TR) group has a significantly decrease compared with that in T and C groups (P < 0.05). Soleus and gastrocnemius muscle mass index in T group increased significantly compared with C group (P < 0.05). Compared with the C group, the ratio of P-p70s6k/p70s6k in T group increased with significant difference (P < 0.05), but the ratio in TR group was significantly reduced (P < 0.05). The ratio of P-rpS6/rpS6 had a significant difference between TR and T group (P < 0.05). These results suggest that the interval training protocol is helpful to increase the relative muscle hypertrophy, and has a role in promoting the expression of p70s6k and rpS6.


Intravenous ketamine for postoperative analgesia.
Thirty-six consecutive patients who had undergone major surgery were carefully studied for 6 hours postoperatively in an attempt to evaluate the relative analgesic and respiratory-depressant effect of morphine, ketamine, and placebo administered by continuous intravenous infusion. Side-effects, vital signs and respiratory measurements were recorded hourly by a consultant physician. With regard to the dosage and method of administration, ketamine was shown to be less effective than morphine for the first 3 hours postoperatively, but equally effective subsequently, whereas the patients who received ketamine showed a greater progressive tendency for their respiratory parameters to improve with time. Recommendations regarding the postoperative control of pain are made, and the need for further study is noted.


ARTIFICIAL SELECTION FOR DEVELOPMENTAL TIME IN DROSOPHILA MELANOGASTER IN RELATION TO THE EVOLUTION OF AGING: DIRECT AND CORRELATED RESPONSES.
A wild-type strain of Drosophila melanogaster was successfully selected for both fast and slow larval development. The realized heritabilities (h2 ) ranged from 0.20 to 0.30 for the fast lines and 0.35 to 0.60 for the slow lines. The selection applied is relevant in relation to the evolution of aging. The longevity of adults, either virgin or mated, was not affected by selection for developmental time, indicating that developmental time is not a causal determinant of life span, thus confirming the results of the studies on environmental effects on aging (Zwaan et al. 1991, 1992). However, adult body weights were higher in the slow developmental lines and lower in the fast lines, relative to the control flies. Furthermore, slow females showed relatively high early fecundity and low late fecundity, as compared with control and fast females. Mated longevities and total lifetime progeny productions were not statistically different. Previous results obtained by other authors from selection experiments on age at reproduction either supported the mutation accumulation or the negative pleiotropy theory of aging (Luckinbill et al. 1984; Rose 1984b). The impact of the reported results on the interpretation of these studies is discussed, and it is noted that direct selection on adult longevity is needed to settle this issue.


The long term (5-years) objective TVT success rate does not depend on predictive factors at multivariate analysis: a multicentre retrospective study.
We evaluated the predictive risk factors that could affect the long-term efficacy of the tension-free vaginal tape (TVT) procedure for the treatment of female stress urinary incontinence (SUI). One hundred thirty-eight (mean age, 52.4+/-9.3 yr) women who underwent the TVT procedure for SUI were selected and followed up for at least 5 yr (mean, 67.2 mo; range, 60-76) after the surgery. We analyzed the preoperative and intraoperative parameters using univariate and multivariate regression for cure rates and patients' satisfaction. The overall 5-yr cure rate was 76.8%, with a satisfaction rate of 86.9%. The cure rates were lower in patients with high body mass index (BMI>or=25 kg/m2/BMI<25 kg/m2=68.3%:83.3%, p=0.044), low abdominal leak point pressure (ALPP<60 cm H2O/ALPP>or=60 cm H2O=51.6%:82.8%, p=0.003), and high grade of SUI (40.0% in grade III; 69.7% in grade II; 86.6% in grade I, p=0.012). On multivariate analysis, there were no independent risk factors related to cure rate, and urgency was the only factor independently associated with patients' satisfaction (p=0.017; odds ratio=4.114). This study demonstrates that the TVT procedure is effective for female SUI without any independent predictive factors affecting long-term cure rate. Urgency was the only predictive factor affecting patient satisfaction. However, high BMI, low ALPP, and high grade of incontinence may impair the cure rate of the TVT.


Healthy lifestyle is associated with reduced cardiovascular disease, depression and mortality in people at elevated risk of sleep apnea.
We assessed: (1) the independent and joint association of obstructive sleep apnea risk and healthy lifestyle with common consequences (excessive daytime sleepiness, depression, cardiovascular disease and stroke) of obstructive sleep apnea; and (2) the effect of healthy lifestyle on survival in people with increased obstructive sleep apnea risk. Data from 13,694 adults (median age 46 years; 50% men) were used for cross-sectional and survival analyses (mortality over 15 years). A healthy lifestyle score with values from 0 (most unhealthy) to 5 (most healthy) was determined based on diet, alcohol intake, physical activity, smoking and body mass index. In the cross-sectional analysis, obstructive sleep apnea risk was positively associated with all chronic conditions and excessive daytime sleepiness in a dose-response manner (p for trend < 0.001). The healthy lifestyle was inversely associated with all chronic conditions (p for trend < 0.001) but not with excessive daytime sleepiness (p for trend = 0.379). Higher healthy lifestyle score was also associated with reduced odds of depression and cardiovascular disease. We found an inverse relationship between healthy lifestyle score with depression (p for trend < 0.001), cardiovascular disease (p for trend = 0.003) and stroke (p for trend = 0.025) among those who had high obstructive sleep apnea risk. In the survival analysis, we found an inverse association between healthy lifestyle and all-cause mortality for all categories of obstructive sleep apnea risk (moderate/high- and high-risk groups [p for trend < 0.001]). This study emphasises the crucial role of a healthy lifestyle in mitigating the effects of obstructive sleep apnea risk in individuals with an elevated obstructive sleep apnea risk.


Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles.
Stem cells possess significant age-dependent differences in their immune-response profile. These differences were analysed by Next-Generation Sequencing of six age groups from bone marrow mesenchymal stem cells. A total of 9,628 genes presenting differential expression between age groups were grouped into metabolic pathways. We focused our research on young, pre-pubertal and adult groups, which presented the highest amount of differentially expressed genes related to inflammation mediated by chemokine and cytokine signalling pathways compared with the newborn group, which was used as a control. Extracellular vesicles extracted from each group were characterized by nanoparticle tracking and flow cytometry analysis, and several micro-RNAs were verified by quantitative real-time polymerase chain reaction because of their relationship with the pathway of interest. Since miR-21-5p showed the highest statistically significant expression in extracellular vesicles from mesenchymal stem cells of the pre-pubertal group, we conducted a functional experiment inhibiting its expression and investigating the modulation of Toll-Like Receptor 4 and their link to damage-associated molecular patterns. Together, these results indicate for the first time that mesenchymal stem cell-derived extracellular vesicles have significant age-dependent differences in their immune profiles.


When Stigma, Disclosure, and Access to Care Collide: An Ethical Reflection of Mpox Vaccination Outreach.
Experiences of stigma in health care encounters among LGBTQ+ populations (lesbian, gay, bisexual, transgender, and queer and questioning) have long been a barrier to care. Marginalization and historically grounded fears of stigmatization have contributed to a reluctance to disclose sexual behavior and/or gender identity to health care providers. We reflect on how student nurses grappled with the ethics of patient disclosure while providing mobile outreach in Chicago for mpox (formerly monkeypox) from fall 2022 to spring 2023. Student nurses addressed how requiring disclosure of sexual behavior or sexual orientation may serve as a barrier to accessing preventive care, such as mpox vaccination. Accounts of stigma and criminalization experienced by LGBTQ+ people provide insight on challenges historically associated with disclosure in health care.