The effect of glucagon-like peptide-1 receptor agonists on serum uric acid concentration: A systematic review and meta-analysis.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications mainly used for the treatment of type 2 diabetes. They improve glucose tolerance, increase insulin secretion and induce weight loss. There is controversy about the effect of GLP-1 RAs on serum uric acid (SUA) concentration. Our systematic review aims to objectively answer whether GLP-1 RAs affect SUA levels. We performed a systematic search on PubMed, Web of Science, Embase, Scopus and Google Scholar datasets up to 27August 2021 with a language restriction of English only. Randomized controlled trials, observational studies, uncontrolled trials and conference abstracts were included. Studies with insufficient data, irrelevant types of study and follow-up duration of less than a month were excluded from the review. After critical appraisal by the Joanna Briggs Institute checklists, articles underwent data extraction using a prespecified Microsoft Excel sheet. Of 1004 identified studies, 17 were eligible for inclusion in this systematic review. Pre- to post-administration analysis of GLP-1 RA effects on SUA demonstrated that GLP-1 RAs could significantly reduce SUA concentration (difference in means -0.341, SE 0.063, P value <0.001). However, when compared to placebo, GLP-1RAs did not perform any better in lowering SUA concentration (difference in means -0.455, SE 0.259, P value 0.079). Surprisingly, the active controls, which included insulin, metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl-peptidase 4 inhibitors, did outperform GLP-1 RAs in reducing SUA concentration (difference in means 0.250, SE 0.038, P value <0.001). Administration of GLP-1 RAs can result in a significant reduction in SUA concentration. However, this reduction is less than that seen with the use of insulin, metformin and SGLT-2 inhibitors.


Association between albumin-corrected anion gap level and the risk of acute kidney injury in intensive care unit.
This study was to investigate the association between albumin-corrected anion gap (AG) (ACAG) levels and the risk of acute kidney injury (AKI) in intensive care unit (ICU) patients. The ICU patients of this retrospective cohort study were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. ACAG = AG + {4.4 - [albumin (g/dl)]} × 2.5. The incidence of AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. The logistic regression model was used to evaluate the association between ACAG levels and the risk of AKI. Subgroup analyses were applied based on age, gender, mechanical ventilation, vasopressors, the Charlson comorbidity index (CCI), and the Simplified Acute Physiology Score II (SAPS II). Totally, 5586 patients were enrolled, of which 1929 patients (34.53%) occurred AKI. The higher levels of ACAG were associated with the risk of AKI in ICU patients, with the odds ratio (OR) value being 1.23 [95% confidence interval (CI): 1.22-1.24, P = 0.005] in ACAG level between 16.5 and 19.5, and OR value being 1.20 (95% CI 1.16-1.24, P = 0.016) in ACAG level > 19.5. A higher ACAG level was associated with a higher risk of AKI in ICU patients aged < 65 years, in ICU patients of female gender, in ICU patients who used mechanical ventilation, in ICU patients who did not use vasopressors, in patients without cardiogenic shock, and in ICU patients with CCI ≥ 2, and SAPS II > 31 (all P < 0.05). There is an association between ACAG level and the risk of AKI in ICU patients. A higher ACAG value in ICU patients should therefore receive more attention.


Water environment in the Tibetan Plateau: heavy metal distribution analysis of surface sediments in the Yarlung Tsangpo River Basin.
To fully understand the environmental quality of sediments in the Yarlung Tsangpo River Basin, surface sediments of the main stream of the Yarlung Tsangpo River and its five major tributaries were studied. In 2016, a total of 201 water samples from the Yarlung Tsangpo River and its tributaries were collected during three water seasons. Fifteen trace elements (including Cd and heavy metals such as Cr, Cu, Pb, and As), which have great environmental effects, were analyzed. The results showed that Ti, Mn, and Cr were the main heavy metals in Yarlung Tsangpo River sediments, accounting for 51%, 10%, and 7% of the total heavy metals, respectively. There were no significant differences among the heavy metal contents in the sediments of Yarlung Tsangpo River among three water seasons, but there were significant spatial variations. During the same period, the concentration of each element in the tributary sediments was generally higher than that in the main stream. According to three different ecological risk assessment models, it is calculated that the heavy metal elements in the surface sediments of the river basin are at low or no pollution risk.


Evaluation of Antibody Tests for Mycobacterium bovis Infection in Pigs and Deer.
This study addressed the need in Great Britain for supplementary blood tests for deer and pig herds under movement restrictions due to confirmed Mycobacterium bovis infection-to enhance the overall sensitivity and reliability of tuberculosis (TB) testing and contribute to an exit strategy for these herds. We evaluated four antibody tests (lateral flow DPP VetTB Assay for Cervids, M. bovis IDEXX ELISA, Enferplex Cervid and Porcine antibody tests and an in-house comparative PPD ELISA) using serum samples from defined cohorts of TB-infected and TB-free deer and pigs. TB-infected deer included two separate cohorts; farmed deer that had received a tuberculin skin test less than 30 days prior, and park deer that had received no prior skin test. In this way, we were able to assess the effect of the skin test anamnestic boost upon antibody test sensitivity. We tested a total of 402 TB-free pigs and 416 TB-free deer, 77 infected farmed deer and 105 infected park deer, and 29 infected pigs (including 2 wild boar). For deer, we found an equivalent high performance of all four tests: specificity range 98.8-99.5% and sensitivity range 76.6-85.7% for skin test-boosted infected deer, and 51.4-58.1% for non-boosted infected deer. These data suggest an overall approximate 25% increase in test sensitivity for infected deer following a skin test boost. For pigs, the tests again had equivalent high specificity of 99-99.5% and a sensitivity range of 62.1-86.2%, with substantial agreement for three of the four tests. Retrospective application of the ELISA tests to individual culled park deer and wild boar that showed no obvious evidence of TB at larder inspection identified a significant seropositivity within wild boar suggestive of low-level M. bovis infection that would otherwise not have been detected. Overall this investigation provided a robust evaluation of four antibody tests, which is essential to generate confidence in test performance before a wider deployment within TB control measures can be considered.


Crash emergency cesarean section: decision-to-delivery interval under 30 min and its effect on Apgar and umbilical artery pH.
The objective of this study was to investigate the effect of decision-to-delivery interval of crash emergency cesarean section on Apgar and umbilical artery pH in a level-3 university hospital. In a retrospective analysis, all women undergoing "crash" emergency cesarean section were evaluated. Emergency cesarean sections were performed in the delivery room. Data relating to indication, Apgar score, arterial cord pH, and time intervals between decision-to-deliver and actual delivery were collected retrospectively. All 109 crash emergency cesarean sections were performed within a decision-to-delivery time of 30 min. The median (with 10-90th percentile) time was 10 min (5-19). Thirty-three (30.3%) of the emergency cesarean sections had a gestational age below 32 weeks and 60 (55%) below 37 weeks. An abnormal fetal heart rate pattern was noted in most of the cases (91%). Prolapsed cord (21%) and placental abruption (20%) were the most frequent reasons for emergency cesarean section but in one-fourth (25.7%) no morphological reason could be identified. Very short decision-to-delivery times below 20 min were inversely correlated to fetal outcome, i.e., lower umbilical blood pH and Apgar scores (P < 0.01). The 30-min standard for the decision-to-delivery time interval set by Anglo-American countries may be a feasible guideline at least for level-3 hospitals. The 20-min interval set by the German Society of Gynecology and Obstetrics could not be achieved in all cases. The positive effect of very short intervals on neonatal outcome still needs to be proven.


Analysis of the adiponectin paradox in healthy older people.
It remains unknown why adiponectin levels are associated with poor physical functioning, skeletal muscle mass and increased mortality in older populations. In 190 healthy adults (59-86 years, BMI 17-37 kg/m2 , 56.8% female), whole body skeletal muscle mass (normalized by height, SMI, kg/m2 ), muscle and liver fat were determined by magnetic resonance imaging. Bone mineral content (BMC) and density (BMD) were assessed by dual X-ray absorptiometry (n = 135). Levels of insulin-like growth factor 1 (IGF-1), insulin, inflammation markers, leptin and fibroblast growth factor 21 were measured as potential determinants of the relationship between adiponectin and body composition. Higher adiponectin levels were associated with a lower SMI (r = -0.23, P < 0.01), BMC (r = -0.17, P < 0.05) and liver fat (r = -0.20, P < 0.05) in the total population and with higher muscle fat in women (r = 0.27, P < 0.01). By contrast, IGF-1 showed positive correlations with SMI (r = 0.33), BMD (r = 0.37) and BMC (r = 0.33) (all P < 0.01) and a negative correlation with muscle fat (r = -0.17, P < 0.05). IGF-1 was negatively associated with age (r = -0.21, P < 0.01) and with adiponectin (r = -0.15, P < 0.05). Stepwise regression analyses revealed that IGF-1, insulin and leptin explained 18% of the variance in SMI, and IGF-1, leptin and age explained 16% of the variance in BMC, whereas adiponectin did not contribute to these models. Associations between higher adiponectin levels and lower muscle or bone mass in healthy older adults may be explained by a decrease in IGF-1 with increasing adiponectin levels.


The association of anticoagulation before admission and survival of patients with COVID-19.
Severe coronavirus disease 2019 (COVID-19) is associated with systematic coagulopathy which might result in fatality. We aimed to investigate whether systematic anticoagulation before admission with COVID infection was associated with patients' survival. We reviewed medical records of 6,095 hospitalized patients with laboratory confirmed COVID-19 from the Mount Sinai Health System. Patients were stratified into two groups: patients with therapeutic anticoagulation before admission (7.9%, N=480), or those without (92.1%, N=5,615). Propensity score matched analysis was conducted to assess the association of anticoagulation before admission and in-hospital mortality (N=296 in each group). Multiple imputation for missing data was conducted. A total of 480 patients (7.9%) received anticoagulation before admission. Patients with anticoagulation before admission were older (72.1±14.7 years vs. 63.1±17.2 years), and had more comorbidities including chronic pulmonary obstructive disease, hypertension, diabetes, chronic kidney disease, atrial fibrillation, and heart failure (all p< 0.05). Notably, patients with anticoagulation before admission had lower D-dimer [1.48 (IQR 0.75, 2.79) μg/mL vs 1.66 (0.89, 3.52) μg/mL, p=0.002]. In a propensity score matched analysis (N=296 in each group), in-hospital mortality was not significantly different in patients with anticoagulation before admission compared to those without (28.4% vs 31.1%, p=0.53). In addition, inverse probability weighted analysis and multiple imputation for missing data did not change the result. Furthermore, these differences were not significant after excluding endotracheal intubation from both groups. Anticoagulation before admission was not associated with lower risk of in-hospital mortality of COVID-19 patients. Further investigation is needed to confirm these findings.


Preproenkephalin mRNA enhanced by combination of droperidol with electroacupuncture.
To study the expression of preproenkephalin (PPE) mRNA following electroacupuncture (EA) combined with droperidol (Dro), an antagonist of dopamine receptors. The brains of Sprague-Dawley rats were sectioned after combination of EA with Dro and nonradioactive in situ hybridization histochemistry (ISHH) technic was used. Ten hours after EA, the expression of PPE mRNA was enhanced; when EA was combined with Dro, the expression of PPE mRNA was further enhanced in many pain-modulation-related nuclei, such as caudate-putamen, accumbens, septal nucleus, diagonal band nucleus, amygdala, hypothalamus, periaqueductal gray (PAG), interpeduncular nucleus, substantia nigra, and the dorsal horn of spinal cord (layer I-II and III-IV). Dro promoted EA's action on the PPE mRNA expression, which underlie the mechanisms of Dro potentiation on acupuncture analgesia.


Power and sample size.
In this chapter, we discuss the concept of statistical power and show how the sample size can be chosen to ensure a desired power. Power is the probability of rejecting the null hypothesis when the null hypothesis is false, that is the probability of saying there is a difference when a difference actually exists. An underpowered study does not have a sufficiently large sample size to answer the research question of interest. An overpowered study has too large a sample size and wastes resources. We will show how the power and required sample size can be calculated for several common types of studies, mention software that can be used for the necessary calculations, and discuss additional considerations.


Water activity influence on aflatoxin accumulation in corn.
The influence of water activity on the production of B1, B2, G1 and G2 aflatoxins in corn has been examined. Viable corn kernels were conditioned at three water activity levels (0.87, 0.90 and 0.97) and inoculated with Aspergillus parasiticus at 30 degrees C. Aflatoxin accumulation was determined at selected times by thin-layer chromatography. For the strain used total aflatoxin accumulation was greater at water activity 0.90 than at 0.87 and 0.97 for the incubation times studied.


Fluorescent amplified fragment length polymorphism (FAFLP) based molecular epidemiology of hospital infections in a tertiary care setting in Hyderabad, India.
Bacterial isolates from respiratory and urinary tract infections in an Indian hospital setting were genotyped using FAFLP analysis. The 77 different isolates analyzed belonged to five genera namely Escherichia, Staphylococcus, Pseudomonas, Enterobacter and Pantoea. Before carrying out FAFLP analysis all the isolates were subjected to16S-23S ribosomal RNA-based species identification. Cluster analysis of FAFLP profiles of 77 isolates generated five groups corresponding to five bacterial genera that are used in the study. Further analyses of the dendrograms revealed efficient species and strain differentiation. Cluster analysis identified genetically distant clones among the clinical isolates of Staphylococcus aureus, two distinct genetic lineages among the Escherichia coli strains and a single cluster of closely related Pseudomonas aeruginosa isolates. Ribosomal spacer region amplification identified different species accurately but intraspecies discrimination could not be accomplished completely. Comparison of FAFLP profiles of our isolates, with a pilot database of validated strains, was very useful in identification and worked better in conjunction with dendrogram analysis.


Periodic orbit analysis reveals subtle effects of atropine on epileptiform activity in the guinea-pig hippocampal slice.
Epileptiform activity is a state often induced in vitro in order to study seizures and antiepileptic/anticonvulsant drugs. Traditional methods of evaluating drug effects have commonly relied upon measuring changes in the frequency and duration of such events. We have used a recently developed mathematical technique based on periodic orbit analysis to investigate the effect of atropine (a muscarinic antagonist) on epileptiform activity induced by soman (an irreversible acetylcholinesterase inhibitor), 4-aminopyridine (a K+ channel blocker) and 8-cyclopentyl-1,3-dipropylxanthine (an adenosine A1 receptor antagonist) in the guinea-pig hippocampal slice. This technique showed that significant changes in periodic orbits can occur without an accompanying change in burst rate. These results suggest that periodic orbit analysis may be useful in detecting and predicting novel actions of anticonvulsant drugs.


The natural history of multiple sclerosis and its diagnosis.
The definition of multiple sclerosis (MS) provides a framework for the findings of the disease. This definition encompasses multiple lesions in the central nervous system which appear over time and emphasizes the spacial distribution of the lesions. Due to the significant degree of variability in the presentation of MS, the definition has evolved in terms of probability for the diagnosis given the findings.


Polymer side-chain degradation as a tool to control the destabilization of polyplexes.
We purposed to design a cationic polymer that binds to pDNA to form polyplexes and that subsequently degrades within a few days at physiological pH and temperature, releasing the DNA in the cytosol of a cell. We synthesized a new monomer carbonic acid 2-dimethylamino-ethyl ester 1-methyl-2-(2-methacryloylamino)-ethyl ester (abbreviated HPMA-DMAE) and the corresponding polymer. Hydrolysis of the carbonate ester of both the monomer and the polymer was investigated at 37 degrees C. The DNA condensing properties of the pHPMA-DMAE was studied using dynamic light scattering (DLS) and zeta potential measurements. Degradation of the polyplexes at 37 degrees C and pH 7.4 was monitored with DLS and gel electrophoresis. In vitro transfections were performed in COS-7 cell line. pHPMA-DMAE is able to condense DNA into small particles (110 nm) with a positive zeta potential. The half-life of the polymer and monomer at 37 degrees C and pH 7.4 was around 10 h whereas at pH 5, the half-life was 380 h. In line with this, due to hydrolysis of the side groups, pHPMA-DMAE-based polyplexes dramatically increased in size at 37 degrees C and pH 7.4 whereas at pH 5.0, only a very small increase was observed. Interestingly, intact DNA was released from the polyplexes after 48 h at pH 7.4 whereas all DNA remained bound to the polymer at pH 5.0. Polyplexes were able to transfect cells with minimal cytotoxicity if the endosomal membrane-disrupting peptide INF-7 was added to the polyplex formulation. Degradation of the cationic side-chains of a polymer is a new tool for time-controlled release of DNA from polyplexes, preferably within the cytosol and/or nucleus.


3-(Benzo[d]thia-zol-2-yl)-2H-chromen-2-one.
In the title compound, C16H9NO2S, the inter-planar angle is 6.47 (6)°. An intra-molecular S⋯O=C contact of 2.727 (2) Å is observed. The packing is determined by several types of weak inter-action ('weak' hydrogen bonds, S⋯S contacts and π-π stacking).


Challenges of scaling-up PHA production from waste streams. A review.
The search for new materials that replace fossil fuel-based plastics has been focused on biopolymers with similar physicochemical properties to fossil fuel-based plastics, such as Polyhydroxyalkanoates (PHA). The present paper reviews the challenges of scaling-up PHA production from waste streams during the period from 2014 to 2016, focusing on the feasibility of the alternatives and the most promising alternatives to its scaling-up. The reviewed research studies mainly focus on reducing costs or obtaining more valuable polymers. In the future, the integration of PHA production into processes such as wastewater treatment plants, hydrogen production or biodiesel factories could enhance its implementation at industrial scale.


Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease.
Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.


Machine learning nonresponse adjustment of patient-reported opioid consumption data to enable consumption-informed postoperative opioid prescribing guidelines.
Post-discharge opioid consumption is a crucial patient-reported outcome informing opioid prescribing guidelines, but its collection is resource-intensive and vulnerable to inaccuracy due to nonresponse bias. We developed a post-discharge text message-to-web survey system for efficient collection of patient-reported pain outcomes. We prospectively recruited surgical patients at Beth Israel Deaconess Medical Center in Boston, Massachusetts from March 2019 through October 2020, sending an SMS link to a secure web survey to quantify opioids consumed after discharge from hospitalization. Patient factors extracted from the electronic health record were tested for nonresponse bias and observable confounding. Following targeted learning-based nonresponse adjustment, procedure-specific opioid consumption quantiles (medians and 75th percentiles) were estimated and compared to a previous telephone-based reference survey. 6553 patients were included. Opioid consumption was measured in 44% of patients (2868), including 21% (1342) through survey response. Characteristics associated with inability to measure opioid consumption included age, tobacco use, and prescribed opioid dose. Among the 10 most common procedures, median consumption was only 36% of the median prescription size; 64% of prescribed opioids were not consumed. Among those procedures, nonresponse adjustment corrected the median opioid consumption by an average of 37% (IQR: 7, 65%) compared to unadjusted estimates, and corrected the 75th percentile by an average of 5% (IQR: 0, 12%). This brought median estimates for 5/10 procedures closer to telephone survey-based consumption estimates, and 75th percentile estimates for 2/10 procedures closer to telephone survey-based estimates. SMS-recruited online surveying can generate reliable opioid consumption estimates after nonresponse adjustment using patient factors recorded in the electronic health record, protecting patients from the risk of inaccurate prescription guidelines.


Measurement data from real operation of a hybrid photovoltaic-thermal solar collectors, used for the development of a data-driven model.
This article presents a measurement dataset from real operation of a hybrid photovoltaic-thermal solar collector. The data is from a summer period, when the collector works at its higher temperature limit, with low thermal efficiency. The dataset characterizes the output of the collector: thermal (heat transfer fluid flowrate, inlet and outlet temperatures) and electrical (raw current and voltage, Hampel filtered power). Further information on the collector are the PV cell temperature and the back surface temperature (in three points). It provides detailed weather information: ambient temperature, solar resource (direct normal, global and diffuse horizontal, global tilted in the collector plane), equivalent radiative sky temperature (calculated from a pyrgeometer), wind speed and direction both horizontal and in the tilted collector plane. The calculated sun position with Duffie and Beckmann method is also given (elevation and azimuth) . The dataset covers 58 summer days from 11th July to 6th September, with a 5 second time step. The data is available as .mat file (MATLAB) and .csv file. A selection of variables from this dataset has already been used in the development of a data-driven model (see related article) [1]. The extended data presented in this article offers mode detailed weather information, opening further investigations opportunities. Further options for data-driven modelling of PVT collectors could be investigated. The correlation of wind related losses to horizontal wind measurements could be compared to a model with wind measurements in the collector plane. The dataset could support the validation of solar models, with direct and diffuse shares on the horizontal or in the tilted plane.


Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art.
Chimeric antigen receptor natural killer cells (CAR-NK) promote off-the-shelf cellular therapy for solid tumors and malignancy.However,, the development of CAR-NK is due to their immune surveillance uncertainty and cytotoxicity challenge was restricted. Natural killer cell-derived exosome (NK-Exo) combine crucial targeted cellular therapies of NK cell therapies with unique non-toxic Exo as a self-origin shuttle against cancer immunotherapy. This review study covers cytokines, adoptive (autologous and allogenic) NK immunotherapy, stimulatory and regulatory functions, and cell-free derivatives from NK cells. The future path of NK-Exo cytotoxicity and anti-tumor activity with considering non-caspase-independent/dependent apoptosis and Fas/FasL pathway in cancer immunotherapy. Finally, the significance and implication of NK-Exo therapeutics through combination therapy and the development of emerging approaches for the purification and delivery NK-Exo to severe immune and tumor cells and tissues were discussed in detail.


The avascular talus: revascularization in an animal model.
Avascular necrosis of bone such as the talus can lead to collapse and loss of function. To avoid this, early revascularization has been proposed as an important event. Revascularization can occur either by vessel growth directly through the bony surface, or by vessel growth into the periosteum or ligaments with secondary reconnection to the bone. The ability to attract new vessels (angiogenesis) of the bony surface and the connective tissue was compared in an animal model. A talus isograft (all cortical surface, periosteum, and ligaments remaining; n = 11) or a sector of a femoral head isograft (cancellous surface, no connective tissue; n = 12) of adult mice was implanted into dorsal skinfold chambers of mice of the same strain. The implants were observed by intravital microscopy every 12 hours. First indicators of angiogenesis were hemorrhages around the implants (tali: 11 of 11, 72 +/- 12 hours; femoral heads: 6 of 12, 84 +/- 24 hours). Next, a sudden redness of the transplant indicated marrow hemorrhage (tali: 9 of 11 after 84 +/- 36 hours; femoral heads: 10 of 12 after 96 +/- 36 hours). Histology showed clear growth of capillaries into the cancellous surface of the femoral heads and possible growth of capillaries into the ligament stumps (tali). However, there was widespread necrosis of the marrow cells indicating failure of recirculation. A cancellous bony surface as well as the soft tissues attached to the bone provided a stimulus to rapid revascularization of the grafts. This model was able to evaluate differing rates of early partial revascularization for various bone surfaces, which may have implications for studying treatment options for certain fracture dislocations (e.g., in the talus).


The role of LCAT and cholesteryl ester transfer proteins for the HDL and LDL structure and metabolism.
Since the early detection of LCAT by Glomset, a great deal of research has been conducted for establishing the role of this enzyme in the Lp metabolism. It became apparent that LCAT produces more than 3/4 of the CE found in plasma. LCAT acts primarily on Lp with high PC/FC contents and high PC/FC ratios. For expression of the full activity, apo-Lp cofactors such as apo-AI, -CI, -AIV and -E are necessary. Although it was believed for a long time that HDL are the only substrate for LCAT we could demonstrate that LDL and even apoA/C/E free LpB is utilized by LCAT. The CE formed in PC/FC rich Lp are transferred to VLDL and LDL by specific proteins, which also promote the exchange of CE against TG. TG in these particles are hydrolyzed by liver lipase providing new space in the core for further cholesterol esterification. Thus LCAT exerts its physiological role in concert with other enzymes e.g. LPL, hepatic lipase and possibly phospho-lipases as well as with exchange and transfer processes partly catalyzed by specific exchange/transfer proteins. The main function of LCAT without doubt is the reverse cholesterol transport from periphery to liver counteracting the accumulation of CE in reticulo endothelial cells by the scavenger pathway. Metabolic studies revealed that the cholesterol clearance from the circulation proceeds in the same order of magnitude as the esterification by LCAT takes place. This possibly implies that LCAT might be the rate limiting enzyme for cholesterol catabolism from blood.


Total mineralization of mixtures of Tartrazine, Ponceau SS and Direct Blue 71 azo dyes by solar photoelectro-Fenton in pre-pilot plant.
Mixtures of monoazo Tartrazine, diazo Ponceau SS and triazo Direct Blue 71 dyes with 105 mg L-1 of total organic carbon (TOC) in 0.050 M Na2SO4 at pH 3.0 have been treated by solar photoelectro-Fenton (SPEF). Experiments were carried out in a 2.5 L pre-pilot plant with a Pt/air-diffusion cell coupled to a solar planar photoreactor. Comparative trials were made by anodic oxidation with electrogenerated H2O2 (AO-H2O2) and electro-Fenton (EF) to better understand the role of oxidizing agents. AO-H2O2 gave poor degradation due to the low oxidation ability of OH formed at the Pt anode and H2O2 produced at the cathode. Similar color removal was achieved in EF and SPEF because the main oxidant was OH formed in the bulk from Fenton's reaction. EF yielded partial mineralization by formation of molecules with high stability against OH. In contrast, these by-products were rapidly photolyzed under sunlight irradiation in SPEF, which was the most powerful treatment. Up to 8 linear final carboxylic acids were detected, along with the release of sulfate and ammonium ions. The effect of Fe2+ and azo dye concentrations, and current density over the SPEF performance was assessed. Total mineralization of azo dyes mixtures occurred when operating up to 105 mg L-1 TOC with 0.50 mM Fe2+ at 100 mA cm-2.


Monitoring cholesterol levels: measurement error or true change?
Cholesterol level monitoring is a common clinical activity, but the optimal monitoring interval is unknown and practice varies. To estimate, in patients receiving cholesterol-lowering medication, the variation in initial response to treatment, the long-term drift from initial response, and the detectability of long-term changes in on-treatment cholesterol level ("signal") given short-term, within-person variation ("noise"). Analysis of cholesterol measurement data in the LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) study. Randomized, placebo-controlled trial in Australia and New Zealand (June 1990 to May 1997). 9014 patients with past coronary heart disease who were randomly assigned to receive pravastatin or placebo. Serial cholesterol concentrations at randomization, 6 months, and 12 months, and then annually to 5 years. Both the placebo and pravastatin groups showed small increases in within-person variability over time. The estimated within-person SD increased from 0.40 mmol/L (15 mg/dL) (coefficient of variation, 7%) to 0.60 mmol/L (23 mg/dL) (coefficient of variation, 11%), but it took almost 4 years for the long-term variation to exceed the short-term variation. This slow increase in variation and the modest increase in mean cholesterol level, about 2% per year, suggest that most of the variation in the study is due to short-term biological and analytic variability. Our calculations suggest that, for patients with levels that are 0.5 mmol/L or more (> or =19 mg/dL) under target, monitoring is likely to detect many more false-positive results than true-positive results for at least the first 3 years after treatment has commenced. Patients may respond differently to agents other than pravastatin. Future values for nonadherent patients were imputed. The signal-noise ratio in cholesterol level monitoring is weak. The signal of a small increase in cholesterol level is difficult to detect against the background of a short-term variability of 7%. In annual rechecks in adherent patients, many apparent increases in cholesterol level may be false positive. Independent of the office visit schedule, the interval for monitoring patients who are receiving stable cholesterol-lowering treatment could be lengthened.


A Scribble/Cdep/Rac pathway controls follower-cell crawling and cluster cohesion during collective border-cell migration.
Collective cell movements drive normal development and metastasis. Drosophila border cells move as a cluster of 6-10 cells, where the role of the Rac GTPase in migration was first established. In border cells, as in most migratory cells, Rac stimulates leading-edge protrusion. Upstream Rac regulators in leaders have been identified; however, the regulation and function of Rac in follower border cells is unknown. Here, we show that all border cells require Rac, which promotes follower-cell motility and is important for cluster compactness and movement. We identify a Rac guanine nucleotide exchange factor, Cdep, which also regulates follower-cell movement and cluster cohesion. Scribble, Discs large, and Lethal giant larvae localize Cdep basolaterally and share phenotypes with Cdep. Relocalization of Cdep::GFP partially rescues Scribble knockdown, suggesting that Cdep is a major downstream effector of basolateral proteins. Thus, a Scrib/Cdep/Rac pathway promotes cell crawling and coordinated, collective migration in vivo.


Stress analysis of pertrochanteric fractures with different fixation devices--behavior under muscle forces and vertical static loading.
The author examined the stress analysis with the strain measuring method on femoral models. We applied static loading with the muscle forces on the frontal plane in a one-legged stance. The results showed that the distribution of the stresses on the surface of the fractured femur revealed an extreme change--"protection phenomenon" at the fracture site in the nail plate group more than in the Ender nails. This may indicate the main transition of the bending force through the devices, resulting in fatigue fracture or breakage of the devices clinically.


Possible Therapies for Hepatocellular Carcinoma-Preparing for the Modern War with the Insidious Enemy.
Hepatocellular carcinoma (HCC) accounts for 7% of all malignancies and about 90% of all primary liver malignancies, making it the most common type of malignant liver neoplasm [...].


Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.
Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.


Addressing Unhealthy Alcohol Use and the HIV Pre-exposure Prophylaxis Care Continuum in Primary Care: A Scoping Review.
Individuals with unhealthy alcohol use are at increased risk for HIV acquisition and may benefit from receiving HIV pre-exposure prophylaxis (PrEP) in primary care settings. To date, literature synthesizing what is known about the impact of unhealthy alcohol use on the PrEP care continuum with a focus on considerations for primary care is lacking. We searched OVID Medline and Web of Science from inception through March 19, 2020, to examine the extent, range, and nature of research on PrEP delivery among individuals with unhealthy alcohol use in primary care settings. We identified barriers and opportunities at each step along the PrEP care continuum, including for specific populations: adolescents, people who inject drugs, sex workers, and transgender persons. Future research should focus on identification of candidate patients, opportunities for patient engagement in novel settings, PrEP implementation strategies, and stigma reduction.


1H, 13C, 15N resonance assignment of the apo form of the small, chitin-active lytic polysaccharide monooxygenase JdLPMO10A from Jonesia denitrificans.
The lytic polysaccharide monooxygenase JdLPMO10A is the N-terminal domain of the multimodular protein Jd1381. The isolated JdLPMO10A domain is one of the smallest chitin-active lytic polysaccharide monooxygenases known to date with a size of only 15.5 kDa. JdLPMO10A is a copper-dependent oxidative enzyme that depolymerizes chitin by hydroxylating the C1 carbon in the glycosidic bond. JdLPMO10A has been isotopically labeled and recombinantly expressed. Here, we report the 1H, 13C, 15N resonance assignment of JdLPMO10A. Secondary structural elements predicted based on the NMR assignment are in excellent agreement with the crystal structure of JdLPMO10A.


Abnormal lipid-linked oligosaccharides in class E Thy-1-negative mutant lymphomas.
The glycosylation defect of Thy-1-mutant lymphomas of the class E complementation group has been identified as a block in the synthesis of the lipid-linked oligosaccharide precursor of the asparagine-linked oligosaccharides of glycoproteins. Two major lipid-linked oligosaccharides were isolated from the mutant cells. Both oligosaccharides were smaller than the lipid-linkid oligosaccharides of wild-type lymphomas and, in contrast to the lipid-linked oligosaccharides isolated from wild-type cells, both were resistant to digestion with endoglycosidase H. The oligosaccharides of newly synthesized polypeptides in class E Thy-1-cells were also resistant to endoglycosidase H digestion, providing strong evidence that they are derived from the abnormal lipid-linked oligosaccharides.


Oral pharmacokinetics and in-vitro metabolism of metyrapone in male rats.
The purpose of this study was to investigate the pharmacokinetics of a single oral administration of metyrapone (MP) and metabolites produced from it in male Wistar rats, and the major tissues and enzymes involved in the production of the MP metabolites. Furthermore, the MP metabolism in human liver subcellular fractions was compared with that in rats. High-performance liquid chromatography with ultraviolet detection (HPLC-UV) was used to determine the concentrations of MP and its metabolites in plasma and urine after administration, and the production activity of MP metabolites in subcellular fractions of various tissues. Plasma concentration of MP was rapidly increased and decreased, and the primary metabolite, metyrapol (MPOL), was immediately produced. The production activity of MPOL was substantially inhibited by an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor in the rat and human liver microsomal and mitochondrial fractions. In the liver cytosolic fraction, the activity was inhibited by a carbonyl reductase inhibitor in the humans but not rats. In this study, we elucidated the plasma pharmacokinetics of MP and its metabolites in male rats after an oral administration. MPOL is most likely to be produced by 11β-HSD1 in the male rats and humans.


Hydrogen peroxide prolongs nuclear localization of NF-kappaB in activated cells by suppressing negative regulatory mechanisms.
NF-kappaB transcription factors induce pro-inflammatory molecules (e.g. IL-8) in response to cytokines (e.g. TNFalpha, IL-1beta) or other stimuli. In the basal state, they are sequestered in the cytoplasm by inhibitory IkappaB proteins. Pro-inflammatory signaling triggers polyubiquitination of intermediaries (e.g. RIP1), which activate IkappaB kinases that trigger Ser phosphorylation and degradation of IkappaBalpha, thereby promoting nuclear translocation of NF-kappaB. A negative feedback loop exists whereby NF-kappaB drives resynthesis of IkappaBalpha, which promotes export of NF-kappaB from the nucleus to the cytoplasm. This process relies on Cezanne, a deubiquitinating cysteine protease that stabilizes resynthesized IkappaBalpha by removing polyubiquitin from modified intermediaries. H(2)O(2) is generated during inflammation. Here we examined the effects of H(2)O(2) on NF-kappaB dynamics and pro-inflammatory activation in cultured cells co-stimulated with TNFalpha or IL-1beta. Quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay revealed that H(2)O(2) enhanced the induction of IL-8 by TNFalpha or IL-1beta. We demonstrated by using assays of NF-kappaB nuclear localization and by imaging of live cells expressing a fluorescent form of NF-kappaB that H(2)O(2) prolonged NF-kappaB nuclear localization in cells co-stimulated with TNFalpha or IL-1beta by suppressing its export from the nucleus. We provide evidence that H(2)O(2) suppresses NF-kappaB export by prolonging polyubiquitination of signaling intermediaries, which promotes Ser phosphorylation and destabilization of newly synthesized IkappaBalpha proteins. Finally, we observed that the catalytic activity of Cezanne and its ability to suppress RIP1 polyubiquitination and NF-kappaB transcriptional activity were inhibited by H(2)O(2). We conclude that H(2)O(2) prolongs NF-kappaB activation in co-stimulated cells by suppressing the negative regulatory functions of Cezanne and IkappaBalpha.


Higher Systemic Immune-Inflammation Index is Associated With Higher Likelihood of Peripheral Arterial Disease.
To explore the association between SII (Systemic Immune-Inflammation Index) and PAD (peripheral arterial disease) in American adults. Related data from NHANES (National Health and Nutrition Examination Survey) database (1999-2004) were collected and analyzed. PAD was diagnosed by ankle brachial index assessment. The association between SII and prevalent PAD was assessed using multivariable logistic regression. A total of 6,576 eligible subjects (including 6117 subjects without PAD and 459 with PAD) were finally enrolled in the study, among which there were 3,187 females and 3,389 males with a mean SII of 585.3 ± 401.5. The age of the subjects with PAD was larger compared to those without PAD (70.2 ± 11.8 vs. 58.7 ± 12.5), and the incidence of chronic diseases, that's CAD, diabetes and hypertension, was higher in those without PAD (P < 0.001). Multivariable logistic regression indicated that a high SII level was an independent risk factor for PAD (OR = 1.51, 95% CI: 1.18- 1.93, P = 0.0012) after adjusting for body mass index, race, sex, age, diabetes mellitus (yes/no), hypertension (yes/no), and cardiovascular disease (yes/no). It is suggested that a higher SII is associated with a higher risk of PAD.


Penile and finger sensory thresholds in young, aging, and diabetic males.
To investigate the possible role of sensory function in conditions affecting sexual function, sensory thresholds were compared between young healthy men (n = 14, means age = 29.8), aging men (n = 15, means age = 67.3), and men suffering from diabetic impotence (n = 15, means age = 45.0). Using the psychophysical method of forced choice, vibrotactile and electrical stimulation thresholds were deterlmined in two separate sessions at two body sites: the fingertip and the ventral surface of the penis, just proximal to the glans. Vibrotactile penile thresholds (VTP) were lowest for young (Y) subjects and much higher for both aging (A) and diabetic (D) subjects. Electrical stimulation of the penis (ESP) showed the same trends, although the differences only approached significance (p = 0.06). The vibrotactile finger threshold (VTF) was significantly higher for A subjects as compared with Y and D subjects, but there was no difference between the Y and D groups. Diabetic patients had significantly higher thresholds for electrical stimulation of the finger (ESF), in contrast to the VTF finding. Finger thresholds were significantly lower than penile thresholds for all groups, and the change in threshold from finger to penis was greater in both aging and diabetic than in young subjects. Age was positively correlated with thresholds for ESF, ESP, VTF, and marginally for VTP when all three groups were analyzed together. However, in general the results of threshold determinations could not be attributed merely to age. Based on a detailed questionnaire of sexuality, VTP was negatively correlated with sexual activity and both ESP and VTP were negatively correlated with erectile capacity. The data are consistent with a genital sensory role for age-related and diabetic changes in sexual function.


Use of Nicardipine After Cardiac Operations Is Safe in Children Regardless of Age.
Control of postoperative hypertension is central to the care of infants and children after cardiac operations. Continuous pharmacologic delivery affords the advantage of rapid onset and ease of titration. Although well established in older children and adults, calcium channel blockers are routinely avoided in children aged younger than 1 year secondary to concerns of safety and efficacy in the setting of sarcoplasmic reticulum development. Thus, the purpose of this study was to review a single-institution experience with nicardipine, a selective calcium channel blocker, in pediatric patients after cardiac operations. Children undergoing cardiac operations at the University of Virginia from 2010 to 2015 were retrospectively reviewed after selection based on receipt of nicardipine for blood pressure management in the postoperative period. Demographic, operative, laboratory, and postoperative data were collected for adverse effect analysis and outcomes comparisons between infants aged younger than 6 months (group 1) and older than 6 months (group 2). During the study period, 68 children (group 1: n = 33 [48%]; group 2: n = 35 [52%]) received nicardipine after cardiac operations (0.5 to 1 μg · kg-1 · min-1). Nicardipine was initiated at a mean of 6.6 ± 13.1 hours postoperatively in group 1 and 5.4 ± 7.8 hours in group 2. Nine patients (13%) demonstrated clinically significant hypotension necessitating dosing titration with no statistically significant differences between groups. No major adverse events occurred following nicardipine administration. Nicardipine is well tolerated after cardiac operations in children irrespective of age or underlying pathology. Thus, nicardipine should be considered as safe and effective in children of all ages for control of hypertension after cardiac operations.


Utilizing Big Data in Cancer Care.
Clinical research has boomed over the past decade, with the development of multiple clinical datasets that are available for retrospective review. However, data remain incomplete based on fragmented reporting, provider change, and loss of follow-up. New technologies are being developed to assist with this limitation, by joining health care systems' medical records, and tracking Medicare claims files. The future of health care will rely more heavily on these systems, and artificial intelligence to quickly pull relevant clinical and genomic data regarding particular diagnoses, as a means to personalize medicine. This article reviews current advances in management of Big Data.


Good recovery after sublethal ethylene glycol intoxication: serial EEG and CT findings.
The case of a young man with sublethal ethylene glycol poisoning is reported. Complete recovery occurred after 12 days of deep coma and a prolonged flaccid tetraplegia. The lesions of gross degree in the CNS, demonstrated by serial CT, resolved and electrophysiological testing as well as neuromuscular signs improved. The recovery, clinically and radiographically, over 35 days was dramatic. Ethylene glycol intoxication should always be considered in the differential diagnosis of acute severe encephalopathy because complete recovery is possible with correct therapy.


Frequency of undiagnosed diabetes mellitus in patients with acute coronary syndrome.
In a prospective cohort of patients who had acute coronary syndrome, we used a simple fasting plasma glucose to identify previously unrecognized diabetes mellitus. A total of 57% of patients who had acute coronary syndrome had abnormal glucose metabolism; approximately 66% of those who met criteria for new diabetes were not diagnosed or treated as such by the physicians who managed them.


Direct oral anticoagulant use and outcomes in adult patients with Fontan circulation: A multicenter retrospective cohort study.
Many adult patients with Fontan circulation are treated with antithrombotic agents, including direct oral anticoagulants (DOACs). However, few studies have investigated the efficacy, feasibility, and safety of DOACs in adult patients with Fontan circulation. In this retrospective cohort study, clinical records of 139 adult patients with Fontan circulation (70 females, 50.4%) from April 2015 to March 2018 were reviewed and classified into five groups according to the therapeutic agents used: DOAC (n = 36), vitamin K antagonist (VKA; n = 41), antiplatelet drug (n = 43), combination of an antiplatelet and anticoagulant (n = 14), and no-antithrombotic prophylaxis (n = 5). In a 1114-patient-year follow-up, 28 major events occurred, including 10 thrombotic and 18 bleeding events; 11 of 18 (61%) female patients had severe menorrhagia. The incidence (% patient-years) of major events was 0.6, 1.42, 3.74, and 5.13 in the DOAC, antiplatelet, VKA, combination, and no-antithrombotic groups, respectively. The Cox proportional hazards analysis revealed that the DOAC group had a lower rate of primary endpoints than the VKA group in males. DOAC may be a safe antithrombotic agent for use in adult patients with Fontan circulation, particularly in males. However, these findings should be confirmed in multi-institutional prospective studies.


[Changes of lens capsule after phacoemulsification].
To observe the changes in the lens capsule after phacoemulsification and its effects on the position of intraocular lens (IOL) and to demonstrate the best position of IOL in relation to the anterior capsule. The present series comprised 141 eyes in 127 patients underwent phacoemulsification and foldable lens implantation with 5 mm continuous curvilinear capsulorhexis. The changes in the lens capsule and the position of IOL with dilated pupil were observed using slit lamp microscope 3 months after the operation. Capsular bag shrinkage and white Soemmering ring along the margin of capsulorhexis were observed in all cases. Three different kinds of relationship between anterior capsule opening and the IOL optic surface were found, including the non-capture (68 eyes), partial-capture (52 eyes) and total-capture (21 eyes) relationships. The incidence of central posterior capsule opacification (PCO) was significantly higher in the total-capture group (47.6%) than that in the non-capture (11.7%) and partial-capture (21.2%) groups (P < 0.01). IOL in well centered position was significantly higher in the non-capture (91.2%) and total-capture (81.0%) groups than that in the partial-capture group (42.3%) (P < 0.01). In the present study, various changes in the lens capsule were observed after phacoemulsification and foldable lens implantation. It is suggested that keeping the IOL in a non-capture position is a key point to avoid the occurrence of PCO and IOL decentration.


Gas chromatographic determination of zopiclone in plasma after solid-phase extraction.
A gas chromatographic technique for determining zopiclone based on a solid-phase extraction procedure with C18 cartridge for sample clean-up is presented. Quantification can be achieved with 1 ml of plasma. The method uses prazepam as internal standard. Zopiclone is separated on a 5% phenyl methyl silicone analytical column and detected with an electron-capture detector, which consequently allows a limit of quantitation of 2 micrograms/l. It is thus simple, rapid, sensitive and linear over the range 5-2000 micrograms/l.


Interactions of a vesicular stomatitis virus G protein fragment with phosphatidylserine: NMR and fluorescence studies.
The interaction of a 19 amino acid vesicular stomatitis virus G protein fragment (GTWLNPGFPPQSCGYATVT) with phosphatidylserine-containing model membranes was investigated using solution-phase 1d and 2d 1H NMR spectroscopy and intrinsic tryptophan fluorescence. Results of these studies show that this peptide interacts with model membranes containing negatively charged phospholipids. The interaction is modulated by both ionic and hydrophobic factors and appears to be dependent on the fluidity and lipid packing of the target bilayer. The data further suggest the existence of two isomeric forms of this peptide, which react differentially with model membranes. Upon binding, 2d 1H NOESY and tryptophan fluorescence data indicate penetration of the tryptophan residue into the bilayer. A model is proposed for the interaction of the peptide with model membranes, consistent with the experimental findings.


Assessing different measures of population-level vaccine protection using a case-control study.
Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses. The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection.


Increased power to detect gene-environment interaction using siblings controls.
Interest is increasing in studying gene-environment (G x E) interaction in disease etiology. Study designs using related controls as a more appropriate control group for evaluating G x E interactions have been proposed but often assume unrealistic numbers of available relative controls. To evaluate a more realistic design, we studied the relative efficiency of a 1:0.5 case-sibling-control design compared with a classical 1:1 case-unrelated-control design and examined the effect of the analysis strategy. Simulations were performed to assess the efficiency of a 1:0.5 case-sibling-control design relative to a classical 1:1 case-unrelated-control design under a variety of assumptions for estimating G x E interaction. Both matched and unmatched analysis strategies were examined. When using a matched analysis, the 1:1 case-unrelated-control design was almost always more powerful than the 1:0.5 case-sibling-control design. In contrast, when using an unmatched analysis, the 1:0.5 case-sibling-control design was almost always more powerful than the 1:1 case-unrelated-control design. The unconditional analysis of the case-sibling-control design to estimate G x E interaction, however, requires no correlation in E between siblings. In most settings, a matched analysis may be required and a 1:1 case-unrelated-control design will be more powerful than a 1:0.5 case-sibling-control design.


Substance abuse in teenagers. Trends and consequences.
Over the past few decades there has been growing concern about the use and abuse of alcohol and other drugs by adolescents. To outline the trends in and consequences of adolescent substance abuse. Alcohol and tobacco remain the most often used drugs in adolescence, and are the drugs associated with greatest morbidity and mortality, but there is some evidence that the use of illicit drugs is increasing. Morbidity and mortality from substance abuse can occur directly from the effects of the drug, from the mode of administration or from environmental factors associated with drug use. Drug related deaths compromise 24% of all deaths in the 12-24 year old age group. This is likely to be an underestimate as alcohol related traffic accidents are excluded from this figure.


Gluteal-related lateral hip pain.
Lateral hip pain (LHP) due to tendon pathologies of insertion of the M. gluteus medius and minimus at the greater trochanter are often misdiagnosed and may lead to unrecognised disability. The purpose of this study was to evaluate pain and patient-reported outcomes in patients presenting with LHP in the context of a publicly financed healthcare system. Data were collected from September 2017 to November 2020 at a regional teaching hospital. Inclusion criteria were clinical and MRI-verified hip abductor tendon pathology. Baseline testing included pain scoring (numerical rating scale, NRS), and the following patient-reported outcome scores: Copenhagen Hip and Groin Outcome Score (HAGOS), Oxford Hip Score (OHS) and EuroQol-Visual Analogue Scale (EQ-VAS). A total of 151 patients (94% women) with a median age of 55 years were included. The mean LHP (NRS 0-10) at rest, during activity and worst pain at any given time was 4, 7 and 9, respectively. The mean patient-reported outcome scores were HAGOS: pain 42.9, symptoms 49.8, activities of daily living 42.2, sport/recreation 28.1, participation in physical activities 25, quality of life 27.8; OHS 24; EQ-VAS 59.6. We found that patients with hip abductor tendon pathology display poor patient-reported outcomes comparable to those of patients suffering from severe hip osteoarthrosis. Further research into this patient group is warranted. The results are based on a heterogeneous study population in terms of variety of hip abductor tendon pathology and comorbidities and need to be interpreted as such. none. According to current Danish law, no formal ethical approval was required for this study. The National Data Protection Agency approved the study (1-16-02-125-19).


Peptidome profiling of umbilical cord plasma associated with gestational diabetes-induced fetal macrosomia.
Fetal macrosomia, defined as a birth weight ≥4000g, may affect 15-45% of newborns of women with gestational diabetes mellitus (GDM). The associations between endogenous peptides and gestational diabetes-induced macrosomia have not been investigated extensively by peptidome analysis. Here, we analyzed the umbilical cord plasma by combining ultrafiltration using molecular weight cut-off filters and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate potential associations of GDM with macrosomia. As macrosomic babies have increased susceptibility to obesity, diabetes and cardiovascular diseases in later life, we also aimed to identify specific biomarkers to detect these future diseases. Thirty pairs of GDM mothers and controls were randomly divided into three subgroups. We identified 235 peptides of around 1000-3000Da, originating from 115 proteins. Analyzing the cleavage sites revealed that these peptides were cleaved in regulation, which may reflect the protease activity and distribution in umbilical cord plasma. Four identified peptides, of 2471.7, 1077.2, 1446.5 and 2372.7Da, were significantly differentially expressed in the GDM macrosomia groups compared with controls, whose precursors may play a critical role in developing GDM macrosomia. We provide for the first time a validated GDM macrosomia peptidome profile and identify potential biomarkers linking the effects of macrosomia to later-life diseases. Fetal macrosomia is the predominant adverse outcome of gestational diabetes mellitus (GDM), which is a frequent medical condition during pregnancy. Till now, the detailed molecular mechanisms underlying gestational diabetes-induced macrosomia are still not elucidated. With high detection sensitivity and high throughput of peptidome technology, it is now possible to systemically identify peptides possibly involved in the umbilical cord plasma of GDM induced macrosomia cases. With LC-MS/MS based quantification, totally, we identified 235 peptides originated from 115 precursor proteins. And four peptides of 2471.7, 1077.2, 1446.5 and 2372.7Da differentially expressed between GDM cases and compared controls. A precursor protein of 1077.2Da was fibrinogen alpha chain (FGA), which was also identified in the Ai et al. [29] study with a downregulated manner in the serum samples of GDM cases. And further analysis the cleavage pattern of the identified peptides revealed that the enzymes in tissues cleaved the protein according to their rules. Thus, this quantitative peptidome approach can identify related peptides that may play a role in the gestational diabetes-induced macrosomia, and give candidate biomarkers contributing to the development of later-life diseases in macrosomic babies.


Evidence for energy reallocation, not oxygen limitation, driving the deceleration in growth of adult fish.
The lifetime growth of almost all fishes follows a biphasic relationship - juvenile growth is rapid and adult growth subsequently decelerates. For a trend that is so ubiquitous, there is no general agreement as to the underlying mechanisms causing adult growth to decelerate. Ongoing theories argue that adult growth slows because either the gills fail to supply the body with surplus oxygen needed for continued somatic gain (i.e. oxygen limited), or sexual maturation induces a switch in energy allocation towards reproduction and away from growth (i.e. energy limited). Here, we empirically tested these notions by tracking the individual growth trajectories of ∼100 female Galaxias maculatus, ranging in size, during their first 3 months of adulthood. At a summer temperature of 20°C, we provided subsets of fish with additional energy (fed once versus twice a day), supplementary oxygen (normoxia versus hyperoxia), or a combination of the two, to assess whether we could change the trajectory of adult growth. We found that growth improved marginally with additional energy, yet remained unaffected by supplementary oxygen, thereby providing evidence for a role for energy reallocation in the deceleration of adult growth. Interestingly, additional dietary energy had a disproportionately larger effect on the growth of fish that matured at a greater size, revealing size-dependent variance in energy acquisition and/or allocation budgets at summer temperatures. Overall, these findings contribute towards understanding the mechanisms driving widespread declines in the body size of fish with climate warming.


Effect of prostate and bony pelvic dimensions measured by preoperative magnetic resonance imaging on robot-assisted radical prostatectomy.
Bone pelvic dimensions and body habitus may have effects on robot-assisted radical prostatectomy (RARP). In this study, we examined the effects of body mass index, bone pelvis measurements and prostate measurements on console time (CT), decrease in postoperative hemogram level (DHL) and surgical margin(SM) in patients who underwent RARP for clinically localized prostate cancer in our institution. The data of transperitoneal RARP cases performed by a single surgeon between November 2016 and August 2020 were analyzed retrospectively. It was included in 125 patients who met the study criteria. Bone and soft tissue measurements were made on magnetic resonance imaging T2-weighted imaging in the mid-sagittal and transvers plane. In multivariate linear regression analyzes, only soft tissue width/transverse diameter of the prostate and CT were found to be correlated (p = 0.026). For the DHL, no pelvic dimension and body habitus had a significant association on multivariate linear regression analysis. In multivariate analyzes, a statistically significant difference was found only between pathological Gleason Score and SM (p = 0.008). Although we found statistically significant associations between prostate diameters and pelvic bone measurements and operative difficulties, we believe that further studies are needed to confirm these results. Such information can help identify patients with challenging anatomy and can be used in robotic surgery training to achieve optimal patient outcomes after RARP.


Peptidoglycan as Nod1 ligand; fragment structures in the environment, chemical synthesis, and their innate immunostimulation.
Covering: up to 2011. This review focuses on the recent revealing of the immunostimulatory bacterial cell wall peptidoglycan (PGN) fragments as Nod1 ligands, especially a newly developed chemical synthesis of the partial structures, fragment structures in the environment and bacterial supernatant, and the immunostimulatory activities of the Nod1 ligands.


Isolation of multipotent progenitor cells from pleura and pericardium for tracheal tissue engineering purposes.
Tissue engineering (TE) of long tracheal segments is conceptually appealing for patients with inoperable tracheal pathology. In tracheal TE, stem cells isolated from bone marrow or adipose tissue have been employed, but the ideal cell source has yet to be determined. When considering the origin of stem cells, cells isolated from a source embryonically related to the trachea may be more similar. In this study, we investigated the feasibility of isolating progenitor cells from pleura and pericard as an alternative cells source for tracheal tissue engineering. Porcine progenitor cells were isolated from pleura, pericard, trachea and adipose tissue and expanded in culture. Isolated cells were characterized by PCR, RNA sequencing, differentiation assays and cell survival assays and were compared to trachea and adipose-derived progenitor cells. Progenitor-like cells were successfully isolated and expanded from pericard and pleura as indicated by gene expression and functional analyses. Gene expression analysis and RNA sequencing showed a stem cell signature indicating multipotency, albeit that subtle differences between different cell sources were visible. Functional analysis revealed that these cells were able to differentiate towards chondrogenic, osteogenic and adipogenic lineages. Isolation of progenitor cells from pericard and pleura with stem cell features is feasible. Although functional differences with adipose-derived stem cells were limited, based on their gene expression, pericard- and pleura-derived stem cells may represent a superior autologous cell source for cell seeding in tracheal tissue engineering.


Occurrence of reducing terminal N-acetylglucosamine 3-sulfate and fucosylated outer chains in acidic N-glycans of porcine zona pellucida glycoproteins.
Structures of acidic N-glycans released from porcine zona pellucida glycoproteins by hydrazinolysis were studied. The results indicated that the acidic glycans are of mono- to tetraantennary complex-type with and without N-acetyllactosamine repeating units. Sulfated residues are not only located at the C-6 position of GlcNAc included in the N-acetyllactosamine repeating units, but also at the C-6 position of GlcNAc in the non-repeated antennae and at the C-3 position of reducing terminal GlcNAc residue. Analysis of the oligosaccharide fragments released by endo-beta-galactosidase digestion and by hydrazine/nitrous acid treatment also revealed that various sulfated and non-sulfated forms of fucosylated structures such as Fucalpha1 --> 2Galbeta1 --> 4(+/-SO3- --> 6)GlcNAc (type 2H), Galbeta1 --> 4(Fucalpha1 --> 3)(+/-SO3- --> 6)GlcNAc(Lex) and Fucalpha1 --> 3 or 4(+/-SO3- --> 6)GlcNAc, are expressed in the repeated outer chain moieties.


Paroxetine decreases respiratory irregularity of linear and nonlinear measures of respiration in patients with panic disorder. A preliminary report.
Previous studies indicate that serotonin reuptake inhibitors do not appear to have serious cardiac side effects. However, the effects of these agents on respiratory measures have not been studied in detail. Several studies indicate that patients with anxiety exhibit irregular breathing patterns as measured by tidal volume and respiratory rate. In this study, we evaluated the effects of a serotonin reuptake inhibitor, paroxetine, on respiratory variability in patients with panic disorder (n = 13), using linear and nonlinear measures of regularity, approximate entropy (APEN) and a measure of chaos, the largest Lyapunov exponent (LLE), with pre- and posttreatment lung volume time series (256 s long sampled at 4 Hz). Our results show that paroxetine significantly decreases some of the linear measures of variability and supine APEN and standing LLE of lung volume series after successful treatment. The implications of these findings on respiratory and cardiovascular function have been discussed.


Liquid-Liquid Phase Separation of Oil Bodies from Seeds.
Fundamentally, oil bodies are discrete storage organelles found in oilseeds, comprising a hydrophobic triacylglycerol core surrounded by a half-unit phospholipid membrane and an outer shell of specialized proteins known as oleosins. Oil bodies possess a number of attributes that were exploited by SemBioSys Genetics to isolate highly enriched fractions of oil bodies through liquid-liquid phase separation for a number of commercial applications. The current chapter provides a general guide for the isolation of oil bodies from Arabidopsis and/or safflower seed, from which protocols can be refined for different oilseed sources. For SemBioSys Genetic's recombinant technology, therapeutic proteins were covalently attached to oleosins or fused in-frame with ligands which bound oil bodies, facilitating their recovery to high levels of purity during "upstream processing" of transformed seed. Core to this technology was oil body isolation consisting of simple manipulation including homogenization of seeds to free the oil bodies, followed by the removal of insoluble fractions, and phase separation to recover the oil bodies. During oil body enrichment (an increase in oil body content concomitant with removal of impurities), a number of options and tips are provided to aid researchers in the manipulation and monitoring of these robust organelles.


AZD6738 decreases intraocular pressure and inhibits fibrotic response in trabecular meshwork through CHK1/P53 pathway.
In this study, we report that AZD6738 (Ceralasertib), a novel potent ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor, can decrease intraocular pressure (IOP) and inhibits fibrotic response in the trabecular meshwork (TM). We established mice TGF-β2-induced high IOP model and revealed that AZD6738 could effectively decrease IOP in the mice model and reduce TGF-β2-induced hyperplasia, collagen production, fibrosis, and extracellular matrix (ECM) remodeling in the TM by downregulating checkpoint kinase 1 (CHK1) level. Further, we demonstrated that AZD6738 reduces cell viability and migration, and inhibit the expression of fibrosis-related factors including fibronectin (FN), α-smooth muscle actin (α-SMA), laminin subunit beta 1 (LAMB1), matrix metallopeptidase (MMP) family including MMP2 and MMP9, collagen Ⅰ (COL1), and collagen Ⅳ (COL4), reduce gap junctions, altered cytoskeleton and nitric oxide production in TGF-β1-induced human trabecular meshwork cells (HTMCs) through the CHK1/P53 pathway, which were affected aqueous humor (AH) production and outflow pathway. In addition, we preliminarily verified the safety of the AZD6738 in topical ophthalmic use. Hence, our results demonstrate that AZD6738 may become a potential therapeutic option for anti-glaucoma.


Is barium esophagram enough? Comparison of esophageal motility found on barium esophagram to high resolution manometry.
The aim of the study is to determine if barium esophagram (BE) alone is sufficient to diagnose esophageal dysmotility when compared to the gold standard, high-resolution manometry (HRM). This is a retrospective review of patients that underwent laparoscopic fundoplication by two surgeons at a single institution from 10/1/2015-6/29/2019. Patients with large paraesophageal hernias and patients without both BE and HRM were excluded. Forty-six patients met the inclusion criteria. BE was found to be concordant with HRM for esophageal motility in only 21 patients (46%). Setting HRM as the gold standard, BE had a sensitivity of 14% (95% CI: 5%-35%), specificity of 72% (95% CI: 52%-86%), PPV of 30% (95% CI: 11%-60%), and NPV of 50% (95% CI: 35%-66%). The accuracy was 46%, while a McNemar test showed p = 0.028. Traditional BE should not be used in place of HRM for assessing pre-operative motility in patients undergoing anti-reflux surgery.


Comparative effects of simvastatin (MK-733) and pravastatin (CS-514) on hypercholesterolemia induced by cholesterol feeding in rabbits.
The preventive effects of simvastatin (MK-733) and pravastatin (CS-514), 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors, on hypercholesterolemia induced by 0.25% cholesterol feeding were compared in rabbits. MK-733 (6, 2 and 0.7 mg/kg) was found to prevent the increase in serum total cholesterol levels dose-dependently. High dose CS-514 (18 mg/kg) also limited the increase in the cholesterol levels, but medium (6 mg/kg) and low doses (2 mg/kg) of CS-514 were ineffective in preventing it. MK-733 inhibited the increase in VLDL and LDL cholesterol levels dose-dependently. MK-733 suppressed the increase in serum phospholipid levels. MK-733 inhibited the accumulation of cholesterol in the liver. The high dose of CS-514 also limited it. High dose MK-733 (6 mg/kg) reduced the cholesterol concentration in gallbladder bile. Neither MK-733 nor CS-514 affected bile acid excretion in the gallbladder bile. High dose MK-733 decreased the lithogenic index. MK-733 increased the number of LDL receptors, and high dose CS-514 also increased it. The suppressive effect of CS-514 on serum cholesterol levels at 18 mg/kg was found to be less than that of MK-733 at 0.7 mg/kg.


Disentangling the effects of attentional difficulties on fears of social evaluation and social anxiety symptoms: Unique interactions with sluggish cognitive tempo.
Although fears of negative and positive social evaluation are hallmark cognitive features of social anxiety, attentional difficulties may exacerbate the relation between fears of social evaluation and social anxiety. Thus, the goal of the current study was to test whether two different types of self-reported attentional difficulties, specifically sluggish cognitive tempo (SCT) and attention-deficit/hyperactivity disorder (ADHD) inattention symptoms, moderate the relation between fears of social evaluation and social anxiety. Participants (N = 4756; Mage = 19.28 years; 72.7% female) enrolled in five universities across the United States completed self-report measures of fears of negative and positive evaluation and psychopathology symptoms. Results indicated a significant two-way interaction of fear of negative evaluation and SCT in relation to social anxiety symptoms, as well as a significant two-way interaction of fear of positive evaluation and SCT in relation to social anxiety symptoms. In both instances, the associations between fears of negative and positive evaluation in relation to social anxiety became increasingly stronger at higher levels of SCT. Conversely, the interactions between fears of negative and positive evaluation with ADHD inattentive symptoms were non-significant. These results are the first to report that self-reported SCT, but not ADHD inattentive symptoms, exacerbate the relation between fears of social evaluation and social anxiety, and suggest that attentional difficulties characteristic of SCT may prolong engagement in fears.


Biogenesis of MalF and the MalFGK(2) maltose transport complex in Escherichia coli requires YidC.
The polytopic inner membrane protein MalF is a constituent of the MalFGK(2) maltose transport complex in Escherichia coli. We have studied the biogenesis of MalF using a combination of in vivo and in vitro approaches. MalF is targeted via the SRP pathway to the Sec/YidC insertion site. Despite close proximity of nascent MalF to YidC during insertion, YidC is not required for the insertion of MalF into the membrane. However, YidC is required for the stability of MalF and the formation of the MalFGK(2) maltose transport complex. Our data indicate that YidC supports the folding of MalF into a stable conformation before it is incorporated into the maltose transport complex.


Ultrasound guidance during hysteroscopic myomectomy in G1 and G2 Submucous Myomas: for a safer one step surgery.
Hysteroscopic myomectomy is the gold standard method for treatment of submucous fibroids. Hysteroscopic myomectomy techniques for removal of submucous fibroids still have controversies. In this study we aimed to describe usefulness of ultrasound guidance in hysteroscopic myomectomy for a safe and effective removal of submucous G1 and G2 fibroids. This is a multicentre study. 64 symptomatic patients with submucous fibroid underwent ultrasound guided hysteroscopic myomectomy. First we excised intrauterine dome of fibroid until reaching the level of cavity wall by the method of resectoscopic (electrosurgical resection using a loop electrode) slicing. Next remnant intramural node was squeezed by uterine contractions induced. After we had excised the intrauterine dome of fibroid by slicing method, we formed cavitation for the intramural part (newly raised myoma dome). The cavity was filled with distension solution and we evaluated the margins of the uterus and the margins of the myoma by sonographically. Then the myoma was excised under ultrasonographic guidance by transabdominal probe. We obtained a regular uterine cavity. Mean operation time was 42±7min. Mean Mannitol volume was 4.3±1.7l and the mean intraoperational fluid deficit was 500ml. Not in any case uterine perforation was occurred. All fibroids removed totally. In 8 (19%) cases intrauterine synechiae detected and all these synechiaes were incised by a scissor during hysteroscopy. There is still no single technique proven to be unequivocally superior to the others for treating fibroids with intramural development (G1-G2). Ultrasound guided hysteroscopy seems to be an effective and safe method for resection of G1 and G2 fibroids.


Organoids.
Organoids have attracted increasing attention because they are simple tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structure and function of the corresponding in vivo tissue. They can be dissected and interrogated for fundamental mechanistic studies on development, regeneration, and repair in human tissues. Organoids can also be used in diagnostics, disease modeling, drug discovery, and personalized medicine. Organoids are derived from either pluripotent or tissue-resident stem (embryonic or adult) or progenitor or differentiated cells from healthy or diseased tissues, such as tumors. To date, numerous organoid engineering strategies that support organoid culture and growth, proliferation, differentiation and maturation have been reported. This Primer serves to highlight the rationale underlying the selection and development of these materials and methods to control the cellular/tissue niche; and therefore, structure and function of the engineered organoid. We also discuss key considerations for generating robust organoids, such as those related to cell isolation and seeding, matrix and soluble factor selection, physical cues and integration. The general standards for data quality, reproducibility and deposition within the organoid community is also outlined. Lastly, we conclude by elaborating on the limitations of organoids in different applications, and key priorities in organoid engineering for the coming years.


Iatrogenic carotid-cavernous fistula following Fogarty catheter thromboendarterectomy. Case report.
A case of iatrogenic carotid-cavernous fistula secondary to a Fogarty catheter thrombectomy is presented. The literature and seven previously reported cases are reviewed.


Resilience and its Predictors among the Parents of Children with Cancer: A Descriptive-Correlational Study.
As a common debilitating illness, cancer is among the leading causes of child mortality in developed and developing countries. Cancer diagnosis for children is considerably stressful for their parents. Resilience is a key factor behind effective coping with cancer-related problems. This study evaluated resilience and its predictors among the parents of children with cancer. This study evaluated resilience and its predictors among the parents of children with cancer. This cross-sectional descriptive-analytical study was conducted in 2017 on 400 parents of children with cancer in Tabriz Children's Hospital, Iran. A demographic questionnaire and the Connor-Davidson Resilience Scale were used to collect the data. Parents were conveniently recruited from Tabriz Children's Hospital. Data were analyzed using the SPSS for Windows program (v. 16) via descriptive and inferential statistical methods. The mean score of parents' resilience was 66.83 ± 14.28. Fathers obtained significantly higher resilience scores than mothers (P < 0.001). The predictors of parents' resilience were financial status, parents' gender, fathers' employment status, and children's gender. The parents of cancer-afflicted children, particularly their mothers, have low resilience and therefore may be at risk for different physical and mental health problems. Health-care providers need to identify at-risk parents and provide them with greater psychological and educational support.


Hemoglobin equilibrium analysis by the multiangle laser light-scattering method.
Dimer-tetramer and monomer-dimer-tetramer equilibria of tetrameric hemoglobins and their single chains in the CO form, respectively, were evaluated using the microbatch multiangle light-scattering (MALS) analysis system. The molecular weights of human Hb A and Hb F in the CO form were dependent on concentration. The dissociation constants to dimers of Hb A and Hb F were 2.58 x 10(-6) and 0.66 x 10(-6), respectively. Equilibration of single globin chains, including alpha, beta, and gamma chains, was also evaluated by the same method. The dissociation constants of alpha-chain dimers to monomers, of beta-chain tetramers to monomers, and of gamma-chain tetramers to dimers were 14 x 10(-6), 25 x 10(-17), and 6.86 x 10(-6) M, respectively. These results indicate that the MALS analysis system can not only determine molecular weight but also characterize protein-protein interactions of multi-subunit proteins.


Opioid-related emergency department visits and deaths after a harm-reduction intervention: a retrospective observational cohort time series analysis.
To date, there has been little research on the effect of safe consumption site and community-based naloxone programs on regional opioid-related emergency department visits and deaths. We sought to determine the impact of these interventions on regional opioid-related emergency department visit and death rates in the province of Alberta. We used a retrospective observational design, via interrupted time series analysis, to assess municipal opioid-related emergency department visit volume and opioid-related deaths (defined by poisoning and opioid use disorder). We compared rates before and after program implementation in individual Alberta municipalities and province-wide after safe consumption site (March 2018 to October 2018) and community-based naloxone (January 2016) program implementation. A total of 24 107 emergency department visits and 2413 deaths were included in the study. After safe consumption site opening, we saw decreased opioid-related emergency department visits in Calgary (level change -22.7 [-20%] visits per month, 95% confidence interval [CI] -29.7 to -15.8) and Lethbridge (level change -8.8 [-50%] visits per month, 95% CI -11.7 to -5.9), and decreased deaths in Edmonton (level change -5.9 [-55%] deaths per month, 95% CI -8.9 to -2.9). We observed increased emergency department visits after community-based naloxone program implementation in urban Alberta (level change 38.9 [46%] visits, 95% CI 33.3 to 44.4). We also observed an increase in urban opioid-related deaths (level change 9.1 [40%] deaths, 95% CI 6.7 to 11.5). The results of this study suggest differences exist between municipalities employing similar interventions. Our results also suggest contextual variation; for example, illicit drug supply toxicity may modify the ability of a community-based naloxone program to prevent opioid overdose without a thorough public health response.


Needle guides for venous catheter insertion during chest compressions: a crossover simulation trial.
Recent guidelines for cardiopulmonary resuscitation emphasize that all rescuers should minimize the interruption of chest compressions, even for intravenous access. We assessed the utility of needle guides during ultrasound-guided central venous catheterization (US-CVC) with chest compressions via simulation. Twenty-five anesthesiologists with more than 2years of experience performed US-CVC on a manikin with or without a needle guide and with or without chest compressions. Insertion success rate within 2minutes, insertion time, and subjective difficulty of venous puncture or guide wire insertion were measured. In normal trials, 1 participant failed US-CVC without compressions, whereas 6 failed with compressions (P=.04). In needle-guided trials, all participants succeeded without compressions, whereas only 1 failed with compressions (P=.31). Insertion time was significantly longer with chest compressions in both normal and needle-guided trials (P<.001, each). Ultrasound-guided central venous catheterization insertion time in normal trials was significantly longer than in needle-guided trials with compressions (P<.001). Difficulty of operation on a visual analog scale for venous puncture or guide wire insertion was significantly higher in normal trials than in needle-guided trials with compressions. Needle guides shortened the insertion time and improved the success rate of US-CVC during chest compressions by anesthesiologists in simulations.


Therapeutic Drug Monitoring and Prolonged Infusions of Ceftolozane/Tazobactam for MDR/XDR Pseudomonas aeruginosa Infections: An Observational Study.
Prolonged infusion of ceftolozane/tazobactam (C/T) is a strategy used to increase achievement of pharmacokinetic/pharmacodynamic targets for the treatment of multi- or extensively drug-resistant MDR/XDR Gram-negative microorganisms. The objective of this study was to describe our therapeutic drug monitoring (TDM) experience of C/T administered by prolonged infusion or intermittent infusion to patients with MDR/XDR Pseudomonas aeruginosa infections. Our outcomes of interest were pharmacokinetic/pharmacodynamic target achievement and clinical cure. Patients with MDR/XDR P. aeruginosa infections treated with C/T were enrolled between February 2018 and February 2020. Blood samples were obtained as part of a TDM program. The pharmacokinetic/pharmacodynamic therapeutic target of C/T was defined as 100% of the duration of the dosing interval that free concentrations are above the minimum inhibitory concentration (MIC) (100 %ƒT ≥ MIC) of the causative pathogen. Dose changes were performed according to TDM results. Forty patients were included: 13 (32.5%) with a proven MDR and 27 (67.5%) with a XDR P. aeruginosa infection. C/T was administered by prolonged infusion in 32 (80%) patients and by intermittent infusion in 8 (20%) patients. Lower doses were administered in the prolonged infusion compared to the intermittent infusion group [3 (9.4%) vs. 5 (62.5%] patients received a dose of 9 g/day (ceftolozane 2 g + tazobactam 1 g, every 8 h; p = 0.004). All patients achieved the pharmacokinetic/pharmacodynamic target and C/T concentrations exceeded 10 × MIC in > 50% of patients in both groups. TDM-recommended dose reductions occurred in 19 (47.5%) patients, being 16 (84.2%) in the prolonged infusion group. A high proportion of patients achieved clinical cure (82.5%). The administration of C/T by prolonged infusion with TDM-guided dosing allowed the achievement of a pharmacokinetic/pharmacodynamic target even at lower doses. C/T showed a high efficacy for treating MDR/XDR P. aeruginosa infections.


Diet and cooling interactions on physiological responses of grazing dairy cows, milk production and composition.
The objective of this trial was to evaluate the effects of diet and cooling in the holding pen before milking on rectal temperature, respiration rate and milk production and composition. Fifty-eight lactating Holstein cows were used in a factorial split-plot design, at Rafaela Experimental Station from 12 January to 3 March 2003. The treatments were combinations of two diets: control (CD) and balanced (BD) with two levels of cooling before milking: none (NSF) and a sprinkler and fans (SF). Forage:concentrate ratios for CD and BD were 81:19 and 68:32, respectively. Cows were milked twice daily. Milk production was recorded daily, and milk composition (fat, protein, lactose and urea) was analysed twice a week. The physiological data were recorded once a week, before the cattle entered the holding pen and after milking, in the afternoon. Average maximum weekly temperature humidity index was 75.4 and ranged from 61.4 to 83. There were highly significant effects of cooling on physiological responses. Milk production was affected by diet and cooling, with no interaction; the highest and lowest production of milk was 22.42 and 20.07 l/cow per day, for BD+SF and CD+NSF, respectively. Protein was affected by diet, and was higher for BD (3.17 vs. 3.08%). There were interaction effects on milk fat at the 8% level, the highest concentration being 3.65% for BD+NFS. It was concluded that under grazing conditions, cooling by sprinkler and fans before milking improves the comfort of dairy cows, and that the effects on milk production and composition are enhanced when diets are specially formulated for heat-stress periods.


Sweet syndrome (acute febrile neutrophilic dermatosis) associated with pulmonary coccidioidomycosis.
Sweet syndrome (acute febrile neutrophilic dermatosis) may arise in association with a variety of underlying systemic diseases. Only 1 case of coccidioidomycosis-associated Sweet syndrome has previously been reported. We describe 2 patients who developed Sweet syndrome during the onset of acute pulmonary coccidioidomycosis. Systemic antifungal therapy was given in both cases. Respiratory symptoms and skin lesions resolved within 5 weeks. Sweet syndrome may be a presenting feature of coccidioidomycosis. Recognition of the underlying pulmonary infection is important so that inappropriate treatment with systemic corticosteroids can be avoided.


Treatment of a calcific bursitis of the medial collateral ligament: a rare cause of painful knee.
Medial knee pain is common in clinical practice and can be caused by various conditions. In rare cases, it can even be by calcific bursitis of the medial collateral ligament (MCL). Treatment of calcific bursitis and/or calcification of the MCL classically includes observation, local injections, shockwave therapy and surgical resection. We report a case of nontraumatic medial knee pain poorly responsive to conservative treatments. Ultrasound (US) imaging revealed a massive lobed hyperechoic formation with partial acoustic shadow in the MCL context compatible with calcific bursitis, and magnetic resonance imaging (MRI) confirmed the presence of the bursa's calcific deposit surrounded by hyperintense signal compatible with pericalcific edema. We performed a double-needle ultrasound-guided percutaneous lavage (UGPL), which is today a fairly common treatment for many musculoskeletal disorders, such as rotator cuff calcific tendinopathy and elbow extensor tendons pathology, but regarding the knee, it is not part of ordinary care. This report shows the clinical and imaging presentation of calcific bursitis of the MCL and describes in detail the technique to perform the UGPL with a system of two needles, two syringes and a double connection to ensure a correct lavage of the calcium deposit without significant intrabursal pressure increase and consequently without pain during the procedure.


Primary non-adherence to bisphosphonates in an integrated healthcare setting.
We estimated primary non-adherence to oral bisphosphonate medication and examined the factors associated with primary non-adherence. Nearly 30% of women did not pick up their new bisphosphonate within 60 days. Identifying barriers and developing interventions that address patients' needs and concerns at the time a new medication is prescribed are warranted. To estimate primary non-adherence to oral bisphosphonate medications using electronic medical record data in a large, integrated healthcare delivery system and to describe patient and prescribing provider factors associated with primary non-adherence. Women aged 55 years and older enrolled in Kaiser Permanente Southern California (KPSC) with a new prescription for oral bisphosphonates between December 1, 2009 and March 31, 2011 were identified. Primary non-adherence was defined as failure to pick up the new prescription within 60 days of the order date. Multivariable logistic regression models were used to investigate patient factors (demographics, healthcare utilization, and health conditions) and prescribing provider characteristics (demographics, years in practice, and specialty) associated with primary non-adherence. We identified 8,454 eligible women with a new bisphosphonate order. Among these women, 2,497 (29.5%) did not pick up their bisphosphonate prescription within 60 days of the order date. In multivariable analyses, older age and emergency department utilization were associated with increased odds of primary non-adherence while prescription medication use and hospitalizations were associated with lower odds of primary non-adherence. Prescribing providers practicing 10 or more years had lower odds of primary non-adherent patients compared with providers practicing less than 10 years. Internal medicine and rheumatology providers had lower odds of primary non-adherent patients than primary care providers. This study found that nearly one in three women failed to pick up their new bisphosphonate prescription within 60 days. Identifying barriers and developing interventions aimed at reducing the number of primary non-adherent patients to bisphosphonate prescriptions are warranted.


Preparation of bio-based porous carbon by microwave assisted phosphoric acid activation and its use for adsorption of Cr(VI).
Ficus carica fiber based activated carbon (FCAC) was used as a potential adsorbent for Cr(VI) removal from aqueous system. The adsorbent was prepared by carbonization of F. carica fiber followed by H3PO4 activation under microwave radiations. The activated carbon was characterized using scanning electron microscopy and Fourier transformer infrared spectroscopy. The adsorption data were well studied for adsorption isotherms, kinetics models, and thermodynamics. Adsorption of chromium ion followed the second-order kinetics and best fitted the Langmuir adsorption isotherms. The maximum adsorption capacity of Cr(VI) onto FCAC was 44.84 mg/g. The calculated values of thermodynamic parameters like enthalpy change (ΔH°), entropy change (ΔS°), and free energy change (ΔG°) were found to be 7.85 kJ/mol, 69.17 J/mol K, and -13.11 kJ/mol, respectively. Adsorption process was spontaneous and endothermic in nature.