Circulating microRNAs as noninvasive biomarkers in breast cancer.
MicroRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation of messenger RNA targets, these non-coding RNAs can modulate the expression of more than half the protein-coding genes in mammalian genomes. MiRNAs play important regulatory roles in a variety of cellular functions and in several diseases, including cancer. Aberrant miRNA expression has been well characterized in cancer, with implications for progression and prognosis. Recently, the discovery of miRNAs in body fluids, such as serum and plasma, opens up the possibility of using them as noninvasive biomarkers of disease and therapy response. In this chapter, we discuss the use of circulating miRNAs as biomarkers of disease and therapy response and as diagnostic and prognostic markers in breast cancer. We also discuss the main issues related to establishing circulating miRNAs as biomarkers in cancer.


The role of total mesorectal excision in the management of rectal cancer.
Total mesorectal excision (TME) was described 20 years ago and is now being established as the therapeutic gold standard for middle and lower third rectal cancers in a number of countries worldwide. The authors reviewed published data regarding TME since its first description in 1982. Emphasis was placed on basic principles, achievable recurrence rates, evidence for use of adjunctive strategies, and the potential of TME. Local recurrence rates following TME approximate 6.6% from published series, accounting for more than 5,000 patients. The available evidence for TME is largely composed of retrospective series, although benefits of TME compare favorably to established conventional controls. Recent studies have clarified the benefit of adjunctive radiotherapy with TME. There is considerable scope for development of TME within the minimal access setting, providing first principles are observed. Despite initial controversy, TME is now a feasible, reproducible, adjunctive surgical therapy in the management of rectal cancer.


The effects of inducers of the endoplasmic reticulum, peroxisomes and mitochondria on the amounts and synthesis of ubiquinone in rat liver subcellular membranes.
Rats were treated with inducers of peroxisomes, mitochondria and the endoplasmic reticulum, as well as receiving diets and drug known to influence the mevalonate pathway. Treatment with clofibrate and 2-diethylhexylphthalate (DEHP) increased microsomal and mitochondrial ubiquinone contents, but a decrease was observed in lysosomes. In vivo labeling of this lipid with [3H]mevalonate was also elevated. The amount of cholesterol did not change upon exposure to these inducers of peroxisomes and mitochondria, but its rate of labeling was decreased. The concentration of dolichol increased only after treatment with DEHP and only in lysosomes. The inducers of the endoplasmic reticulum phenobarbital, 3-methylcholanthrene and N-nitrosodiethylamine enhanced the rate of ubiquinone synthesis and exposure to the latter two substances also elevated the amount of this lipid in microsomes. A cholesterol-rich diet increased the labeling of ubiquinone and decreased cholesterol labeling, while cholestyramine treatment had opposite effects on lipid labeling in both microsomes and mitochondria. The results demonstrate that the ubiquinone contents of the various membranes of hepatocytes change in a characteristic manner under the influence of inducers and dietary factors. Clearly, the level of ubiquinone and its biosynthesis are regulated separately from those of the other products of the mevalonate pathway, cholesterol and dolichol.


CT appearance of bilateral, acute thrombosis of the main cerebral arteries.
Acute thrombosis within the lumen of the intracranial artery may occasionally be demonstrated on precontrast CT. The hyperdensity follows the course of the occluded segment of the vessel and an area of low attenuation in the territory of the involved artery is usually present, consistent with infarction. Usually, a single vessel is involved; occlusion of multiple branches occurs less commonly. This report demonstrates a case of diffuse bilateral thrombosis of the main arteries of the anterior circle of Willis.


Possible biological control of ash dieback using the mycoparasite Hymenoscyphus fraxineus mitovirus 2.
Invasive fungal diseases represent a major threat to forest ecosystems worldwide. As the application of fungicides is often unfeasible and not a sustainable solution, only a few other control options are available, including biological control. In this context, the use of parasitic mycoviruses as biocontrol agents of fungal pathogens has recently gained particular attention. Since the 1990s, the Asian fungus Hymenoscyphus fraxineus has been causing lethal ash dieback across Europe. In the present study, we investigated the biocontrol potential of the mitovirus Hymenoscyphus fraxineus mitovirus 2 (HfMV2) previously identified in Japanese populations of the pathogen. HfMV2 could be successfully introduced via co-culturing into 16 out of 105 HfMV2-free isolates. Infection with HfMV2 had contrasting effects on fungal growth in vitro, from cryptic to detrimental or beneficial. Virus-infected H. fraxineus isolates whose growth was reduced by HfMV2 showed overall a lower virulence on ash (Fraxinus excelsior) saplings as compared to their isogenic HfMV2-free lines. The results suggest that mycoviruses exist in the native populations of H. fraxineus in Asia that have the potential for biological control of ash dieback in Europe.


A case of mixed ductal-endocrine carcinoma of the pancreas.
A 66-year-old male patient underwent a stomach-preserving pancreatoduodenectomy procedure because of a tumor located around the lower bile duct under the diagnosis of carcinoma of the lower bile duct. The tumor (3.5 × 2.5 cm) was found at the head of the pancreas and had invaded the papillae of Vater at the duodenum. Histology findings indicated both ductal adenocarcinoma and endocrine tumor. The ductal adenocarcinoma component expressed carcinoembryonic antigen, cytokeratin (CK)-19, CK-20, carbohydrate 19-9, and amylase, whereas the endocrine component, which occupied about one-third of the tumor, expressed glucagon, neuron-specific enolase, and chromogranin A. The Ki-67 labeling indices of the two components were 49.7% and 5.3%, respectively. Herein, we present this case of mixed ductal-endocrine carcinoma of the pancreas. Our findings indicate that its aggressive mass may be ascribable to the adenocarcinoma component with a high proliferative potential.


SARS-CoV-2's claimed natural origin is undermined by issues with genome sequences of its relative strains: Coronavirus sequences RaTG13, MP789 and RmYN02 raise multiple questions to be critically addressed by the scientific community.
RaTG13, MP789, and RmYN02 are the strains closest to SARS-CoV-2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS-CoV-2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where the PRRA insertion in SARS-CoV-2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6-nucleotide deletion in the region and that the 12-nucleotide insertion in SARS-CoV-2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS-CoV-2's origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods.


L-lactate promotes intestinal epithelial cell migration to inhibit colitis.
Lactate, one of the most common primary metabolites of bacteria and human cells, has been shown to play essential roles in the regulation of inflammatory diseases, including inflammatory bowel diseases. However, whether and how host-derived lactate affects intestinal epithelial homeostasis is still not completely understood. Here, we investigated how L-lactate, mainly produced by host cells, regulates intestinal epithelial cell (IEC) migration to promote intestinal wound healing. Using video microscopy and tracking individual cells, we found that L-lactate enhanced IEC migration in direction persistence and speed. Mechanistically, L-lactate promoted IEC mitochondrial ATP production. The mitochondrial ATP synthase inhibitor, oligomycin, significantly decreased IEC persistence and speed, which inhibited cell migration induced by L-lactate. Furthermore, administering mice with L-lactate suppressed colitis induced by dextran sulfate sodium. In conclusion, our study demonstrates that host-derived L-lactate promotes IEC mitochondrial ATP production to drive cell migration, promoting intestinal wound healing to alleviate intestinal inflammation.


Enantioselective Selenol-ene Using Rh-Hydride Catalysis.
This study showcases the first enantioselective hydroselenation of styrenes. Organoselenium building blocks are accessed with selectivity for the branched isomer. Through a Rh-hydride pathway, C-Se bonds can be forged with excellent regio- and enantiocontrol.


Physical and imaging performance of SIAT aPET under different energy windows and timing windows.
The performance of small animal PET scanners depends on the energy window (EW) and timing window (TW). In National Electrical Manufacturers Association (NEMA) Standards Publication NU 4-2008, detailed procedures of the performance measurements are defined, but the EW and TW are not specified. In this work, the effects of EW and TW on the physical and imaging performance of Shenzhen Institute of Advanced Technology small animal PET (SIAT aPET) will be evaluated. First, the flood histogram, energy resolution, and timing resolution were measured for a detector of SIAT aPET. Second, the spatial resolutions were measured with different EWs. Third, the sensitivities, the scatter fractions (SFs), and noise equivalent count rates (NECRs) of a mouse-sized phantom and a rat-sized phantom, the recovery coefficients (RCs) of rods of different sizes, and the percentage standard deviation (%STD) of the NEMA image quality phantom were measured for different EWs and TWs. Last, images of a hot rod phantom, a mouse heart, and a rat brain were acquired from the scanner with different EWs. The SIAT aPET detectors provided good flood histograms such that all but the corner crystals can be resolved even with lower energies of 250-350 keV, an average energy resolution of 21.1 ± 1.9%, and an average timing resolution of 2.63 ± 0.69 ns. The average spatial resolutions obtained with EWs of 250-350 keV and 450-550 keV are 0.68 mm and 0.75 mm. For EWs of 250-750 keV, 350-750 keV, and 450-750 keV with a fixed TW of 12 ns, the sensitivities at the center of field of view (FOV) are 16.0%, 11.9%, and 8.2%, the peak NECRs of a mouse-sized phantom are 355.6 kcps, 324.4 kcps, and 249.4 kcps, and the peak NECRs of a rat-sized phantom are 148.5 kcps, 144.3 kcps, and 117.7 kcps, respectively. For the TWs of 4 ns, 8 ns,12 ns, and 20 ns with a fixed EW of 350-750 keV, the sensitivities at the center of FOV are 9.6%, 11.4%, 11.9%, and 12.2%, the peak NECRs of a mouse-sized phantom are 260.1 kcps, 311.5 kcps, 324.4 kcps and 324.9 kcps, and the peak NECRs of a rat-sized phantom are 110.5 kcps, 137.3 kcps, 144.3 kcps, and 142.6 kcps, respectively. Narrowing the EW and TW improves the RCs of rods of all sizes, and the %STD of images obtained with different EWs and TWs are similar. Rods with diameter down to 0.8 mm can be visually resolved from images of the hot rod phantom obtained with different EWs. Images of mouse heart with high spatial resolution and rat brain with detail brain structure were obtained with different EWs. Images of both phantom and in vivo animals obtained with different EWs only showed subtle difference. The performance of SIAT aPET under different EWs and TWs was compared. The EW and TW affect the sensitivity, SF, and NECR but not the spatial resolution and animal images of SIAT aPET, which imply that careful optimization of the EW and TW is not required.


In vivo autoradiography: visualization of stress-induced changes in opiate receptor occupancy in the rat brain.
A method of in vivo autoradiography was utilized which allows the visualization of local changes in opiate receptor occupation in the intact rat brain. The method is based on the exclusion of [3H]diprenorphine binding in areas in which the release of endogenous opiate peptides is increased by behavioral manipulation. The technique lends itself to the use of film autoradiography, allowing the mapping of relative levels of functional receptor occupancy throughout the whole brain. Prolonged intermittent footshock and forced swims in cold water (two stress-inducing manipulations which are known to release endogenous opiates) were found to cause highly significant decreases in specific high-affinity [3H]diprenorphine binding, as measured by liquid scintillation counting. These changes were unaccompanied by corresponding changes in non-specific binding and were not related to local changes in blood flow. A prolonged non-stressful swim in warm water caused no changes in [3H]diprenorphine binding. The use of tritium-sensitive film autoradiography allowed the resolution of these decreases to the level of individual nuclei. Differences in specific binding were found to be greatest in the periaqueductal gray, the reticular formation, and in midline-intralaminar thalamic nuclei, all of which have been implicated in the modulation of pain sensation.


Epidermal growth factor receptor and DNA double strand break repair: the cell's self-defence.
The purpose of this review is to discuss the relation between the repair of DNA double strand breaks (DSB)--the main lethal lesion inflicted by ionising radiation-and the function of receptors of epidermal growth factor (EGFR) and similar ligands (other members of the ERBB family). The reviewed experimental data support the assumption that in mammalian cells, one consequence of EGFR/ERBB activation by X-rays is its internalisation and nuclear translocation together with DNA-dependent protein kinase (DNA-PK) subunits present in lipid rafts or cytoplasm. The effect of EGFR/ERBB stimulation on DSB rejoining would be due to an increase in the nuclear content of DNA-PK subunits and hence, in activity increase of the DNA-PK dependent non-homologous end-joining (D-NHEJ) system. Such mechanism explains the radiosensitising action of "membrane-active drugs", hypertonic media, and other agents that affect nuclear translocation of proteins. Also, one radiosensitising effect of the recently introduced into clinical practice EGFR/ERBB inhibitors would consist on counteracting the nuclear translocation of DNA-PK subunits. In result, D-NHEJ may be less active in inhibitor-treated cells and this will contribute to an enhanced lethal effect of irradiation. The reviewed observations point to a heretofore not understood mechanism of the cell's self-defence against X-rays which can be exploited in combined radio- and chemotherapy.


Shotgun metagenomic analysis of bacterial symbionts associated with "Chromodoris quadricolor" mantle.
Nudibranchs are colorful marine invertebrates having a diverse group of understudied animals. Recently, some nudibranch members have acquired some attention while others still have not. Chromodoris quadricolor is a member of the Red Sea nudibranch, which did not have the chance to get significant attention. Unlike various invertebrates, it lacks a shell suggesting that it must defend itself in other ways. Therefore, in the present study, we were concerned about the mantle-associated bacterial communities. Being essential partners of this dorid nudibranch system, we investigated their taxonomic and functional profiles. We performed a whole metagenomic shotgun approach for the mantle bacterial cells after a differential pelleting procedure. In this procedure, we separated most of the prokaryotic cells from the eukaryotic host cells. Our findings showed that the mantle-body part holds a diverse group of bacterial species relating mainly to Proteobacteria and Tenericutes phyla. There were novel findings regarding the bacterial members associated with the nudibranch mollusks group. Various species were not previously recorded as bacterial symbionts with nudibranchs. Those members were Bathymodiolus brooksi thiotrophic gill symbiont (23.2%), Mycoplasma marinum (7.4%), Mycoplasma todarodis (5%), and Solemya velum gill symbiont (2.6%). The presence of these bacterial species assumed a nutritional role to the host. However, some of these species were present in a high abundance, suggesting their important symbiosis with Chromodoris quadricolor. In addition, exploring the bacterial ability to produce valuable products resulted in the prediction of 2088 biosynthetic gene clusters (BGCs). We identified different gene cluster classes. Polyketide BGC class was the most represented. Others were related to fatty acid BGCs, RiPP, saccharide, terpene, and NRP BGC classes. Prediction of the activity of these gene clusters resulted in, mainly, an antibacterial activity. In addition, different antimicrobial secondary metabolites were also detected. These secondary metabolites are considered key components regulating the bacterial species interactions in their ecosystem. This suggested the significant contribution of these bacterial symbionts to protect the nudibranch host against predators and pathogens. Globally, it is the first detailed study concerned with both the taxonomic diversity and functional potentials of the bacterial symbionts associated with Chromodoris quadricolor mantle.


Proteomic differences in the hippocampus and cortex of epilepsy brain tissue.
Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioural disorders, and increased mortality from direct (e.g. sudden unexpected death in epilepsy, accidents, drowning) or indirect effects of seizures and therapies. Extensive research with animal models and human studies provides limited insights into the mechanisms underlying seizures and epileptogenesis, and these have not translated into significant reductions in pharmaco-resistance, morbidities or mortality. To help define changes in molecular signalling networks associated with seizures in epilepsy with a broad range of aetiologies, we examined the proteome of brain samples from epilepsy and control cases. Label-free quantitative mass spectrometry was performed on the hippocampal cornu ammonis 1-3 region (CA1-3), frontal cortex and dentate gyrus microdissected from epilepsy and control cases (n = 14/group). Epilepsy cases had significant differences in the expression of 777 proteins in the hippocampal CA1 - 3 region, 296 proteins in the frontal cortex and 49 proteins in the dentate gyrus in comparison to control cases. Network analysis showed that proteins involved in protein synthesis, mitochondrial function, G-protein signalling and synaptic plasticity were particularly altered in epilepsy. While protein differences were most pronounced in the hippocampus, similar changes were observed in other brain regions indicating broad proteomic abnormalities in epilepsy. Among the most significantly altered proteins, G-protein subunit beta 1 (GNB1) was one of the most significantly decreased proteins in epilepsy in all regions studied, highlighting the importance of G-protein subunit signalling and G-protein-coupled receptors in epilepsy. Our results provide insights into common molecular mechanisms underlying epilepsy across various aetiologies, which may allow for novel targeted therapeutic strategies.


LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease.
Mutations in the leucine-rich repat kinase 2 (LRRK2) gene have been shown to cause both autosomal dominant and sporadic Parkinson's disease (PD). The common G2019S mutation shows wide geographical distribution while R1441G has been only reported in Northern Spain. The overall frequency of these mutations remains to be established. To determine the prevalence of G2019S and R1441G mutations in our population of Cantabria (Northern Spain), we recruited 105 consecutive PD patients and 310 controls and conducted genetic analysis of these mutations. G2019S was detected in eight late-onset patients (7.6%). Five of them had no relevant family history. R1441G was not detected in any of our study subjects. The prevalence of G2019S mutation in unselected late-onset PD patients might be higher than previously reported: 3/16 (18.7%) of familial PD and 5/82 (6.1%) of sporadic PD.


Genotype-phenotype correlations in alpha-sarcoglycanopathy: a systematic review.
Mutations in the alpha-sarcoglycan gene cause limb-girdle muscular dystrophy 2D, an autosomal recessive muscle wasting disorder primarily affecting the muscles of the shoulder and pelvic girdles. To date, no previous study has collated all known mutations in alpha-sarcoglycan and mapped these to the associated phenotypes. To examine for correlations between mutation locations, or mutation type, and the phenotype caused in all reported mutations in alpha-sarcoglycan. We present a systematic literature review examining correlations between mutation locations, or mutation type, and the phenotype caused in all reported cases of limb-girdle muscular dystrophy 2D. From 134 unique genotypes collated, a strong prevalence of missense mutations (64% of all unique mutations) was found in this gene. Mutation hotspots were noted in exon three and the extracellular domain, with mutation densities varying significantly between both exons and protein domains (p ≤ 0.01). All compound heterozygous limb-girdle muscular dystrophy 2D patients with cardiac involvement contained at least one mutation in exon three, a novel finding. All non-sense mutations in alpha-sarcoglycan give a severe phenotype, as do genotypes involving a combination of exons four and five. This study confirms on a large, diverse cohort the extremely high prevalence of the c.229C > T mutation. This study demonstrates the vast variation in disease severity seen between patients possessing the same mutation, highlighting the difficulty identifying genotype-phenotype correlations in this condition. Novel findings including the involvement of exon three in all compound heterozygous patients who suffered from cardiomyopathy, and the severity of mutations involving exons four and five may help to guide investigations and therapeutic decisions in an era of personalised medicine.


The Use of Veress Needle and 10-mm Trocar (VN) Versus Direct Trocar Insertion (DTI) in the Beginning of Laparoscopy
Seven hundred fifty-six women were randomly divided into two groups. Group 1 (378 cases) were operated on via laparoscopy with VN and group 2 (378 cases) with DTI technique. Complications were compared between the two groups. No major complications occurred. Minor complications were: a problem with insufflation of CO2 (19 VN, 2 DTI, P<0.001); more than one insertion of the instrument (18 VN, 13 DTI, NS); need to alter the technique (6 VN, 10 DTI, NS); and penetration of the fascia but not the peritoneum by trocar sleeve (2 VN, 19 DTI, P<0.001). The significant differences found presented no serious problems, and we concluded that both methods were satisfactory.


Construction of oxygen vacancy assisted Z-scheme BiO2-x/BiOBr heterojunction for LED light pollutants degradation and bacteria inactivation.
It is well known that the most important task of photocatalytic technology is to synthesize photocatalysts with compact heterojunction structure and high redox ability. To achieve the goal, a novel Z-scheme BiO2-x/BiOBr heterojunction containing oxygen vacancy was synthesized by an in-situ generation process. Several techniques, X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) have verified the BiO2-x/BiOBr heterojunction. XPS and electron spin resonance (ESR) reveals the presence of oxygen vacancy in the BiO2-x/BiOBr composite. As expected, the BiO2-x/BiOBr composite showed good performance in removing Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Rhodamine B (RhB) and tetracycline (TC). The effects of inorganic ions, pH value and water matrix were investigated with many details. The active species and proposed mechanism were revealed by trapping experiment and related characterizations. The synergistic effect of oxygen vacancy and Z-scheme heterojunction makes the BiO2-x/BiOBr composite possess excellent photocatalytic activity.


Soil quality indicators response to application of hydrophilic polymers to a soil from a sulfide mine.
In soils impacted by mining activities a vegetal cover is required to protect the site from the erosive forces of water and wind. The success of this objective depends on plant establishment and canopy closure. Polyacryalate polymers aid the growth of crops and indigenous plants in soils from sulfide mines. Soil characteristics change as a consequence of polymer application, but indicators that pinpoint these changes have not been identified yet. Our objectives were to (1) identify the sensitive indicators of changes in soil quality following polymer application, (2) relate these with assessment based on plant growth and soil cover. A mine soil was left unamended or received a characterized polyacrylate, a polyacrylate removed from diapers, or shredded diapers. Biomass of Spergularia purpurea was measured and proportion of soil cover evaluated. Soil enzymes, microbial activity, and respiration were analyzed. Availability of potentially toxic trace elements was estimated by their concentration in shoots. Factor analysis identified three factors that accounted for 94% of the variation in parameters, and the scores separated the four treatments. The indicators with greatest communality were correlated with plant growth and soil cover. The best soil quality indicators were As and Zn in shoots, protease, β-glucosidase, and fructose-induced respiration. It seems that the most important indicators to be used to assess the restoration of sulfide mine soils are those related with bioavailability of trace elements and soil enzymatic activities.


A simple and inexpensive method for laryngeal photography with the operating microscope.
After a brief review of the history of laryngeal photography, a simple and inexpensive method as used at the ENT Clinic of Ljubljana is described. The equipment consists of a standard 35 mm Olympus OM-1 camera attached to the Olympus of OME-J operating microscope and an Olympus T-32 flash unit connected via a large bore flexible light cable to a specially designed laryngoscope. With the equipment described excellent photographs can be obtained even in inexperienced hands without interference with endoscopic procedures.


Differential heat shock gene expression in chick blastula.
The component areas of chick blastula show differential expression of heat shock genes. The area opaca (ao), marginal zone (mz) and central area (ca) components of the epiblast display distinct quantitative and minor qualitative differences in the heat-induced and heat-repressible proteins, but are clearly different from the primary hypoblast (endoderm) in their expression of a given stress protein (hsp) as a response to heat shock. The major proteins synthesized in the component areas of epiblast in response to heat shock include hsp 18, 24, 70 and 89 Kd. Two-dimensional electrophoresis shows that each of these proteins consists of multiple charged species. The hypoblast expresses only hsp 70 Kd at non-significant levels and shows marked inhibition in the level of synthesis of heat-shock-repressible proteins. Heat shock during the blastula stage results in an increase in the size of the blastoderm and disrupts normal embryonic development. The heat shock genes provide an important molecular marker, which attests to regional specification in the chick blastula.


No statistical evidence that honey bees competitively reduced wild bee abundance in the Munich Botanic Garden-a comment on Renner et al. (2021).
In a recent paper, Renner et al. (Oecologia 195:825-831, 2021) concluded, without supporting statistical evidence, that increased density of managed honey-bee hives between 2019 and 2020 intensified competitive effects of honey bees on non-Apis bee species in the Munich Botanic Garden. Analysis of Renner et al.'s observations revealed that, contrary to their assumption, the change in hive numbers did not statistically alter honey-bee visitation to 29 plant species within or between years. Given this consistency, changes in the proportion of non-Apis bees among visitors of the surveyed plant species between years likely represent their responses to reduced overall availability of floral resources during 2020. Thus, Renner et al.'s observations do not provide convincing evidence that honey bees competitively reduced the abundance of non-Apis bees in the Munich Botanic Garden.


Endplate structure and parameters of neuromuscular transmission in sporadic centronuclear myopathy associated with myasthenia.
Centronuclear myopathy is a pathologically diagnosed congenital myopathy. The disease genes encode proteins with membrane modulating properties (MTM1, DNM2, and BIN1) or alter excitation-contraction coupling (RYR1). Some patients also have myasthenic symptoms but electrodiagnostic and endplate studies in these are limited. A sporadic patient had fatigable weakness and a decremental EMG response. Analysis of centronuclear myopathy disease- and candidate-genes identified no mutations. Quantitative endplate electron microscopy studies revealed simplified postsynaptic regions, endplate remodeling with normal nerve terminal size, normal synaptic vesicle density, and mild acetylcholine receptor deficiency. The amplitude of the miniature endplate potential was decreased to 60% of normal. Quantal release by nerve impulse was reduced to 40% of normal due to a decreased number of releasable quanta. The safety margin of neuromuscular transmission is compromised by decreased quantal release by nerve impulse and by a reduced postsynaptic response to the released quanta.


Stage-, dose-, and course-dependent inhibition of prenatal amoxicillin exposure on fetal articular cartilage development in fetal mice.
Amoxicillin is widely used in the treatment of infectious diseases during pregnancy; however, the effects of prenatal amoxicillin exposure (PAE) on fetal development remain largely unknown. Therefore, this study aimed to investigate the toxic effects of PAE on fetal cartilage at different stage-, dose-, and course. Pregnant Kunming mice were orally administered 300 mg/kg·d (converted from clinical dose) amoxicillin on gestational days (GD) 10-12 or 16-18 (mid or late pregnancy stage), 150 or 300 mg/kg.d amoxicillin on GD16-18 (different doses), 300 mg/kg·d amoxicillin on GD16 (single course) or 16-18 (multiple courses), respectively. The fetal articular cartilage of the knee was collected on GD18. The number of chondrocytes and the expression of matrix synthesis/degradation, proliferation/apoptosis-related markers, and the TGF-β signaling pathway were detected. The results showed that the number of chondrocytes and the expression of matrix synthesis markers were reduced in male fetal mice treated with PAE (GD16-18, 300 mg/kg.d, single course and multiple courses), whereas the above indices in female mice showed no changes. The inhibited expression of PCNA, increased expression of Caspase-3, and down-regulated expression of the TGF-β signaling pathway were found in male PAE fetal mice. Accordingly, PAE exerted its "toxic effect window" on the knee cartilage development in male fetal mice, which manifested as reduced chondrocyte number and inhibited expression of matrix synthesis at a clinical dose of multiple courses in the late pregnancy stage. This study provides a theoretical and experimental basis for elucidating the risk of chondrodevelopmental toxicity associated with amoxicillin during pregnancy.


Determination of pepper microbial contamination for low energy e-beam irradiation.
Electrons with energies of 300 keV or lower have the potential to decontaminate the surfaces of various types of food products with minimal loss of quality. The aim of the present work was to determine the thickness of the layer inhabited by microorganisms. The food samples tested were black and white pepper irradiated with 200 keV, 230 keV, 300 keV and 9 MeV beams of electron energy. To determine the depth from the surface which can be inhabited by microorganisms two approaches were tested. The methods used were based on the application of different microbiological recovery techniques and the microbial effectiveness of the irradiation process depending on the energy of the electron beam. It was observed that the layer which microorganisms may contaminate differed for the tested samples it was estimated as being below 100 μm thick for white pepper and about 200 μm for black pepper. The penetration ability was significant in experiments performed, and as a result the electron beam at the lowest levels tested (200 and 230 keV) was found to be insufficient to effectively decontaminate the black pepper samples. The beam of energy 300 keV was found to have a similar microbial inactivation effect as the high energy electron beam (9 MeV).


Early clinical results of cementless, bipolar hemiarthroplasty in intracapsular femur neck fractures.
In this study we report our initial experience with the use of cementless, bipolar hemiarthroplasty in elderly patients with intracapsular femur neck fractures. We operated 67 consecutive patients (39 females, 28 males; mean age 74.4±11.0 years; range 41 to 99 years) who admitted to our clinic June 2007 and November 2009, due to intracapsular femur neck fracture and implanted cementless, rectangular, dual-taper, straight femoral stem (Zweymüller stem) with bipolar head prosthesis. All patients were allowed to full weight bearing with a walker within the first postoperative 48 hours. According to the Garden's classification, there were nine type II, 53 type III and five type IV fractures. Twelve patients were lost to follow-up and 21 deceased during the postoperative follow-up period. Among 34 patients with complete follow-up, 30 were evaluated for the clinical outcome. The mean follow-up time and Harris hip score of the evaluated patients were 19.4 months and 79.4 points, respectively. It was seen that, the patient age significantly correlated with the clinical outcome and a better mean hip score was obtained in the '70 years and younger age group' (83.6 points) as compared to the 'older than 70 years age group' (75.6 points) (p=0.014). Mortality rate was found to be higher in patients older than 70 years (47% vs. 18%; p=0.036) and with displaced fractures (45% vs. 0%; p=0.018). Zweymüller cementless bipolar hemiarthroplasty may be an alternative treatment method for intracapsular femur neck fractures especially in the patients under the age of 70 years.


Pressor, tachycardic and behavioral excitatory responses in conscious rats following ICV administration of ACTH and CRF are blocked by naloxone pretreatment.
Experiments were conducted to compare the blood pressure and heart rate responses of conscious rats given intracerebroventricular (ICV) injections of adrenocorticotropin (ACTH 1-24) and corticotropin releasing factor (CRF). Under sodium pentobarbital anaesthesia, rats were implanted with a stainless-steel cannula into the lateral cerebral ventricle and had their right femoral artery and vein cannulated. Upon recovery (24-48 hr later) conscious, unrestrained rats were given ICV injections (total volume 5 microliter by gravity flow) of sterile saline, ACTH (1-24) (0.85 and 1.7 nmoles) or CRF (0.55 and 1.1 nmoles) and blood pressure and heart rate were monitored over the next 2 hr (from the abdominal aorta via the femoral arterial catheter). Both ACTH and CRF caused mean arterial pressure (MAP) to increase, which was paralleled with increases in mean heart rate (MHR). Moreover, these elevations in MAP and MHR were temporally associated with excessive grooming (for ACTH) and locomotor activity (for CRF), which occurred before and lasted as long as MAP and MHR were enhanced. Intravenous (IV) pretreatment whereby naloxone was given 10 min before ICV administration of ACTH (1.7 nmoles) or CRF (1.1 nmoles), showed that naloxone blocked the behavioral, pressor and tachycardic effects of both ACTH and CRF. The results demonstrate that the pressor, tachycardic and locomotor effects evoked in conscious rats by ICV administration of ACTH or CRF are antagonized by naloxone and that their hemodynamic changes may, in part, be mediated by prior behavioral activation.


Impact of human capital and financial globalization on environmental degradation in OBOR countries: Critical role of national cultural orientations.
As regional economic integration and climate change are among the most important phenomena influencing economic and social sustainability in the modern world, a huge volume of research is directed towards these topics nowadays. The aim of this study is to explore the impact of financial globalization and human capital on environmental degradation in One Belt One Road (OBOR) countries in a cultural context that is largely under-explored in spite of being immensely crucial for fulfilling the United Nations' agenda on climate change mitigation. Owing to the presence of vast cultural differences, we check if the national scores on "Power Distance Index" and "Uncertainty Avoidance" in these countries matter for the environment. To this end, we use the latest and annual data set comprising 31 OBOR countries from 1996 to 2018, and employ panel econometric techniques that effectively deal with the threat of endogeneity. Results show that human capital improves environment while financial globalization deteriorates it. Interestingly, high power distance and uncertainty avoidance can reverse the positive impact of human capital. Similarly, financial globalization is favorable for environment in countries with low power distance and uncertainty avoidance. The findings are robust to the use of alternative specifications. Theoretical underpinnings and implications are discussed arising from the interesting reversal of traditional impacts in different cultural scenarios. Specifically, we recommend a culture of entrepreneurship, innovation, and inclusivity, promoted through increased tolerance towards risk-taking and participative decision-making to reap the benefits of human capital and globalization in improving the environment. Our results have important implications for climate change mitigation endeavors in OBOR countries and understanding the cultural context in this regard. Additionally, our study opens a vast avenue for the related research work in the future.


Establishing a prediction model for recurrence of condyloma acuminatum.
We collected the clinical data of 156 patients diagnosed with condyloma acuminatum (CA), including age, gender, marriage, education level, stay up late, smoking, drinking, number of sexual partners, HPV infection status of sexual partners, genitourinary and anal diseases, condom use, other diseases of HPV infection, location and number of warts, HPV typing, etc. Analyze the risk factors affecting the recurrence of CA, explore the influencing factors and independent influencing factors of CA recurrence, establish the prediction model of CA recurrence, and evaluate its prediction value. Univariate analysis showed that stay up late, HPV infection status of sexual partners, urogenital diseases, condom use, other diseases of HPV infection and the number of CA were the influencing factors of CA recurrence. Multivariate analysis showed that condom use (OR = 0.166), HPV infection status of sexual partners (OR = 4.848), number of warts (OR = 1.212) and urogenital diseases (OR = 3.179) were independent factors affecting the recurrence of CA (P < 0.05). Therefore, the prediction model of CA recurrence can be established, and the area under the curve AUC of the prediction model was calculated to be 0.867 (95% CI 0.812-0.923). The model established in this study has certain prediction value for the recurrence of CA and can be used to preliminarily predict the recurrence of CA.


Prevalence of intolerance to food additives.
Food additives have been implicated as aetiological factors in many different disease states. Concern arose from a suggested link with food additives and hyperactivity in children. They have also been implicated in many other disease states. This perception, often made by parents on behalf of their children, is not confirmed by double-blind placebo-controlled challenge studies. The discrepancy between public perception and the true prevalence of food additive reactions is great and this discrepancy between perception and confirmed reactions also exists with food-related symptoms. The discrepancy is much greater in the case of food additives than in foods. The mechanism of food additive reactions is not immunological and there is no in vivo or in vitro confirmatory test.


Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation.
To review outcome measures including overall survival (OS), progression free survival (PFS), and patterns of recurrence in patients with advanced vulvar cancer managed by primary surgery (PS) or primary chemoradiation (PCRT) as well as population characteristics for the two groups. Patients diagnosed with stage III and IV squamous cell carcinoma of the vulva from 1990 to 2006 were identified for retrospective analysis at a single institution. Charts were abstracted for clinical and pathologic findings, treatment modalities, complications, recurrence, and follow-up. Kaplan-Meier method was used to determine PFS and OS. Sixty-three patients with stage III (n=47) and IV (n=16) carcinoma of the vulva were identified; 30 patients were treated with PS, and 33 patients had tumor that was unresectable by vulvectomy and underwent PCRT. Patients treated with PCRT were younger (61 vs. 72 years; p=0.09), had less metastasis to lymph nodes (54% vs. 83%, p=0.01), and larger tumors (6 vs. 3.5 cm, p=0.0001) compared to patients treated with PS. Despite these differences, OS for the PS and PCRT groups was 69% and 76% (NS), respectively, with median follow-up at 31 months. There were no differences in PFS or recurrence rates between the two groups. By multivariate analysis, age was the only significant predictor of OS or PFS. Patients with advanced vulvar cancer that are managed with PS tend to be older patients that have smaller lesions but positive lymph nodes, whereas patients requiring PCRT are younger and have larger volume disease but fewer lymph node metastases. Despite these differences, patients treated with PS and PCRT have no differences in OS, PFS, or recurrence rates. Age is the most powerful predictor of survival when size, lymph node status, stage and treatment are accounted for.


Current approaches to the diagnosis and management of choroidal melanomas.
Although malignant melanoma of the uveal tract is well known as the most common primary intraocular malignancy, many questions exist regarding the best approach to its diagnosis and treatment. In the past, diagnosis has been made by direct ophthalmoscopy alone and errors resulting in unnecessary enucleation have been frequent. However, recent studies have shown that the adequate use of new techniques such as indirect ophthalmoscopy, fluorescein angiography, ultrasonography, and the 32P test can reduce the incidence of error substantially. A 12-step procedure for diagnosis utilizing these aids is outlined. Traditionally, enucleation has been accepted as the treatment of choice. However, with earlier and more accurate diagnosis, alternative treatments are being applied in selected cases. Although photocoagulation, irradiation, cryotherapy, diathermy and local resection of choroidal melanomas have been used with some success, these methods require further trial and followup before their value can be established. Techniques and indications for use of these procedures are discussed, and the complications and potential effectiveness of each is evaluated.


Supramolecular synthon pattern in solid clioquinol and cloxiquine (APIs of antibacterial, antifungal, antiaging and antituberculosis drugs) studied by ³⁵Cl NQR, ¹H-¹⁷O and ¹H-¹⁴N NQDR and DFT/QTAIM.
The quinolinol derivatives clioquinol (5-chloro-7-iodo-8-quinolinol, Quinoform) and cloxiquine (5-chloro-8-quinolinol) were studied experimentally in the solid state via ³⁵Cl NQR, ¹H-¹⁷O and ¹H-¹⁴N NQDR spectroscopies, and theoretically by density functional theory (DFT). The supramolecular synthon pattern of O-H···N hydrogen bonds linking dimers and π-π stacking interactions were described within the QTAIM (quantum theory of atoms in molecules) /DFT (density functional theory) formalism. Both proton donor and acceptor sites in O-H···N bonds were characterized using ¹H-¹⁷O and ¹H-¹⁴N NQDR spectroscopies and QTAIM. The possibility of the existence of O-H···H-O dihydrogen bonds was excluded. The weak intermolecular interactions in the crystals of clioquinol and cloxiquine were detected and examined. The results obtained in this work suggest that considerable differences in the NQR parameters for the planar and twisted supramolecular synthons permit differentiation between specific polymorphic forms, and indicate that the more planar supramolecular synthons are accompanied by a greater number of weaker hydrogen bonds linking them and stronger π···π stacking interactions.


Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice.
TNF-alpha and IL-6 are generally increased in the sera of aged humans and mice. The dysregulation of these cytokines may be critical in autoreactivity and immune dysfunction. In earlier studies we demonstrated that production of TNF-alpha and IL-6 following in vitro stimulation of peritoneal macrophages by LPS was reduced in old compared to young mice, and that dietary caloric restriction (CR) had no effect on the induction of TNF-alpha in this system. In the present study we examined the effects of age and calorie restriction on the constitutive production of both TNF-alpha and IL-6. Serum levels of both cytokines were significantly higher in old versus young mice. However, in old mice subjected to long term CR the serum levels were comparable to those of young mice. The potential involvement of normalization of TNF-alpha and IL-6 levels in the life extension effect of CR are discussed.


The Effect of Core Stabilization Exercise on the Kinematics and Joint Coordination of the Lumbar Spine and Hip During Sit-to-Stand and Stand-to-Sit in Patients With Chronic Nonspecific Low Back Pain (COSCIOUS): Study Protocol for a Randomized Double-Blind Controlled Trial.
Chronic nonspecific low back pain (CNLBP) is among the most prevalent health problems. Lumbar spine and hips kinematics and coordination can be affected in CNLBP. The effects of exercises on the kinematics and coordination of lumbar spine and hips during sit-to-stand (STS) and its reverse have not been evaluated. The aim of this study is to investigate the effect of core stabilization exercise on the kinematics and joint coordination of the lumbar spine and hip during STS and its reverse in CNLBP patients. COSCIOUS is a parallel randomized double-blind controlled trial. A total of 30 CNLBP patients and 15 asymptomatic participants will be included. The kinematics and joint coordination of the lumbar spine and hips will be evaluated during STS and its reverse using a motion capture system. The participants will be asked to sit in their usual posture on a stool. Reflective markers will be placed over the T12, S2, anterior and posterior superior iliac spines, greater trochanters, and lateral femoral epicondyles of both legs. The participants will be instructed to stand up at natural speed, remain in the erect posture for 3 seconds, and then sit down. Kinematic variables of the lumbar spine and hip will be computed. Afterward, the CNLBP participants will be allocated at random to receive one of 2 interventions: core stabilization or general exercise. Treatment sessions will be held 3 times per week for 16 sessions. After intervention, CNLBP participants will be assessed again. Funding for the study was provided in 2016 by Iran University of Medical Sciences. The study is expected to last approximately 12 months, depending on recruitment. Findings on the study's primary outcomes are expected to be finalized by December 2017. The results of the study will be published in a peer-reviewed journal. This investigation will evaluate the effects of core stabilization exercise on the kinematics and joint coordination of the lumbar spine and hip during STS and its reverse in patients with CNLBP. In addition, the effects of CNLBP on STS and its reverse will be investigated in COSCIOUS. Iranian Registry of Clinical Trials IRCT2016080812953N2; http://en.search.irct.ir/view/32003?format=xml (Archived by WebCite at http://www.webcitation.org/6qjTWd4Az).


Implant experience with an implantable hemodynamic monitor for the management of symptomatic heart failure.
Management of congestive heart failure is a serious public health problem. The use of implantable hemodynamic monitors (IHMs) may assist in this management by providing continuous ambulatory filling pressure status for optimal volume management. The Chronicle system includes an implanted monitor, a pressure sensor lead with passive fixation, an external pressure reference (EPR), and data retrieval and viewing components. The tip of the lead is placed near the right ventricular outflow tract to minimize risk of sensor tissue encapsulation. Implant technique and lead placement is similar to that of a permanent pacemaker. After the system had been successfully implanted in 148 patients, the type and frequency of implant-related adverse events were similar to a single-chamber pacemaker implant. R-wave amplitude was 15.2 +/- 6.7 mV and the pressure waveform signal was acceptable in all but two patients in whom presence of artifacts required lead repositioning. Implant procedure time was not influenced by experience, remaining constant throughout the study. Based on this evaluation, permanent placement of an IHM in symptomatic heart failure patients is technically feasible. Further investigation is warranted to evaluate the use of the continuous hemodynamic data in management of heart failure patients.


A comprehensive electromagnetic evaluation of an MRI anthropomorphic head phantom.
Electromagnetic simulations are an important tool for the safety assessment of RF coils. They are a useful resource for MRI RF coil designers, especially when complemented with experimental measurements and testing using physical phantoms. Regular-shaped (spherical/cylindrical) homogeneous phantoms are the MRI standard for RF testing but are somewhat inaccurate when compared with anthropomorphic anatomies, especially at high frequencies. In this work, using a recently developed anthropomorphic heterogeneous human head phantom, studies were performed to analyze the scattering parameters (S-parameters) and the electric and magnetic field distributions using (1) the B1+ field mapping method on a 7 T human MRI scanner and (2) numerical full-wave electromagnetic simulations. All studies used the following: a recently developed six-compartment refillable 3D-printed anthropomorphic head phantom (developed from MRI scans obtained in vivo), where the phantom itself is filled in its entirety with either heterogeneous loading, or homogeneous brain or water loading, in vivo imaging, and a commercial homogeneous spherical water phantom. Our results determined that the calculated S-parameters for all the anthropomorphic head phantom models were comparable to the model that is based on the volunteer (within 17% difference of the reflection coefficient value) but differed for the commercial homogeneous spherical water phantom (within 45% difference). The experimentally measured B1+ field maps of the anthropomorphic heterogeneous and homogeneous brain head phantoms were most comparable to the in vivo measured values. The numerical simulations also show that both the anthropomorphic homogeneous water and brain phantom models were less accurate in terms of electric field intensities/distributions when compared with the segmented in-vivo-based head model and the anthropomorphic heterogeneous head phantom model. The presented data highlights the differences between the physical phantoms/phantom models, and the in vivo measurements/segmented in-vivo-based head model. The results demonstrate the usefulness of 3D-printed anthropomorphic phantoms for RF coil evaluation and testing.


Fetal and neonatal fatality in rat hybrids from mothers stimulated with parental skin.
A breeding experiment was conducted in which MAXX female rats were mated with BN male rats. These two strains of inbred rats are identical for AgB antigens and differ only in antigens governed by minor histocompatibility loci. MAXX females, which were exposed before pregnancies to four BN skin grafts, delivered 117 offspring of which 28 (23.9%) were stillborn and 10 (8.5%) dead within 24 hr of birth. In contrast, of 126 offspring in control groups, only one was stillborn and one dead within 24 hr. In BN-grafted MAXX females, placentas were partially necrotic with marked polymorphonuclear reaction, which could account for stillbirths or the newborn deaths shortly after birth. The stillborn fetuses had grossly noticeable wrinkled skin. Histologically, the architecture of the epidermis was disturbed. The dermis was edematous and contained occasional mononuclear cells.


Interference-free electrocatalysis of p-chloro meta xylenol (PCMX) on uniquely designed optimized polymeric nanohybrid of P(EDOT-co-OPD) and fMWCNT modified glassy carbon electrode.
p-Chloro-meta-Xylenol (PCMX) is an environmentally hazardous phenolic compound having biocidal and antiseptic activity. Very few research publications addressed monitoring this contaminant. This paper presents a rapid sensing system to quantify it in waste water samples. The electrochemical activity of PCMX was exploited through a unique polymeric nanocomposite modified transducer for its quantification. Poly[(3,4-Ethylenedioxythiophene)-co-(o-phenylenediamine)] [P(EDOT-co-OPD)] was deposited through one-step electropolymerization technique on the glassy carbon electrode (GCE) modified by functionalized multi-wall carbon nanotubes (fMWCNTs). An optimized combination of these constituents was evaluated using response surface methodology (RSM) based Box-Behnken experimental design. This maximized the response for PCMX using differential pulse voltammetry (DPV). The sensing matrix was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The structural and morphological study of the modified film was conducted by Fourier transform-infrared spectroscopy (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), and field emission scanning electron microscope (FESEM). The anodic peak current could be read from a wide range of 0.5-225 μM calibration curve with a detection limit of 0.2545 μmol L-1. Interestingly this work did not use any biomaterial in the modification but achieved interference-free response with excellent selectivity, sensitivity (0.4668 μA μM-1 cm-2), reproducibility (RSD = 2.2%), and repeatability. The sensing platform showed good stability (85.7%) of 3 months even after 150 times repetitive use. Its applicability for real samples was established by good correlation with standard methods.


The immediate and subsequent impact of a first-time traumatic anterior shoulder dislocation in people aged 16-40: Results from a national cohort study.
Limited evidence exists which details changes in quality of life, shoulder activity level, kinesiophobia, shoulder pain and disability following a first-time traumatic anterior shoulder dislocation (FTASD) in people treated non-operatively. This study had three objectives: (1) to examine quality of life, pain, disability and kinesiophobia after an FTASD within 12 weeks, (2) to examine whether these variables were different in people with and without recurrent shoulder instability and (3) to assess how these variables changed over 12 months. A prospective cohort study was undertaken in people with an FTASD aged between 16 and 40 years. Measures of quality of life, kinesiophobia, shoulder activity, shoulder pain and disability were recorded within 12 weeks of an FTASD and at 3, 6, 9 and 12 months. An FTASD negatively impacted quality of life, shoulder pain and function and these variables improved over time. People with recurrent shoulder instability had poorer quality of life 12 months after an FTASD. Across the entire cohort, kinesiophobia did not significantly change across time in people following an FTASD. Quality of life was significantly affected by an FTASD in people with recurrent shoulder instability. Across the entire cohort of people with an FTASD, kinesiophobia remained elevated in people following an FTASD. Level 1 prognostic study.


Assessment of beef production from Brahman x Thai native and Charolais x Thai native crossbred bulls slaughtered at different weights. I: growth performance and carcass quality.
Effects of genotype and slaughter weight on growth performance and carcass quality of Brahman x Thai native (BRA) and Charolais x Thai native (CHA) crossbred bulls were studied. Thirty-four BRA and 34 CHA bulls raised under practical fattening beef farm conditions were randomly selected and slaughtered at 500, 550 and 600 kg live weight, respectively. Parameters of growth performance, carcass quality and commercial prime cuts were determined. Results showed that growth performance and carcass quality of CHA was better, since they showed higher weight gain, better body muscle score, higher carcass weight high dressing percentage, higher carcass muscle, less carcass fat and bone plus connective tissue proportions, better carcass classifications, greater loin eye area and higher commercial prime cut percentage. Slaughter weights up to 600 kg resulted in increased carcass weight, loin eye area and percentage of commercial prime cuts and can therefore be recommended.


Transfer of Ephedra genomic DNA to yeasts by ion implantation.
The genomic DNA from Ephedra glauca was randomly transferred to Saccharomyces cerevisiae and Hansenula anomala by argon and nitrogen ion implantation. Through repeated subculturing and using reversed phase high-performance liquid chromatography analysis to quantify the concentrations of the secondary metabolites, l-ephedrine and d-pseudoephedrine, 12 recombinant strains of genetically stable yeast were obtained, each using glucose as a carbon source, NaNO3 as a nitrogen source and producing l-ephedrine and/or d-pseudoephedrine. After culturing in liquid medium for 72 h, extracellular l-ephedrine and d-pseudoephedrine concentrations of 18.85 and 4.11 mg/L, respectively, were detected. Using l-ephedrine and d-pseudoephedrine as the target products, the transformation efficiencies of the genomic DNA from E. glauca transferred to S. cerevisiae and H. anomala were 1.15% (1/87) and 2.13% (8/376), respectively. The addition of the amino acid, L-Phe, to culture media substantially changed the amount of l-ephedrine and/or d-pseudoephedrine produced by the recombined yeasts. However, the change in metabolite production was not consistent among strains, rising in some, while dropping to nondetectable levels in others. After random amplification of polymorphic DNA (RAPD) analysis, four RAPD primers were obtained from the initial 100 RAPD primers, each amplifying different fragments with the recombined yeast Ar_Han0458 genome. Using one primer as polymerase chain reaction primer, the result showed that the recombined yeast Ar_Han0458 genome matched E. glauca genomic DNA at 150 bp, indicating a successful transfer of genetic information, facilitated by ion implantation.


[Relation between lymph flow and pressure in the interstitium and the degree of hydration of the lungs].
In 25 isolated canine lungs perfused through the pulmonary or bronchial vessels, lung lymph flow and interstitial pressure of the alveolar and peribronchium interstitium were studied. Lung lymph flow in both kinds of perfusion is the function of interstitial pressure which supports the convectional theory of lymph genesis in the lung. The data obtained reveal considerable distinctions between alveolar and peribronchial interstitial spaces fluid pressure-volume characteristics which determine qualitative features of lymph transport.


Isolation of simian virus 40 from rhesus monkeys (Macaca mulatta) with spontaneous progressive multifocal leukoencephalopathy.
Isolates of virus from the brain tissue of two naturally occurring cases of progressive multifocal leukoencephalopathy in rhesus monkeys (Macaca mulatta) have been characterized. Both isolates were demonstrated to be simian virus 40 (SV40) by serological tests and analysis of cleavage fragments of viral deoxyribonucleic acid produced by restriction endonuclease from Haemophilus influenzae. SV40 virions and the nonvirion T antigen were demonstrated in the brain lesions of one monkey by the fluorescent antibody staining technique. SV40 was not demonstrated in the brain of normal rhesus monkeys from the same colony with use of the same methods of viral isolation or demonstration of antigen.


A modified method for rapid quantification of Chlamydia muridarum using Fluorospot.
Although manual enumeration of Chlamydia inclusion forming units is the most widely accepted means of quantification in the field, it is both time consuming and subject to inherent investigator bias. We report here a rapid, i.e., minutes vs. hours, modified automated Fluorospot means of assessment that is linear (<1200 dots per well). Because the Fluorospot enumerated tissue culture plate/well can also be quantified using traditional manual counting, newly derived Fluorospot data can easily be compared to previously established manual enumeration data requiring no new reference norms. •Concurrent enumeration of chlamydial IFU using automated and manual methods of counting on same tissue culture plate.•Rapid method of counting chlamydial IFU reducing time from hours to minutes.


Optimising the self-assembly of siRNA loaded PEG-PCL-lPEI nano-carriers employing different preparation techniques.
Amphiphilic cationic block copolymers consisting of poly(ethylene glycol), poly(ε-caprolactone) and poly(ethylene imine) spontaneously assemble to nano-sized particulate carriers, which can be utilised for complexation of nucleic acids (small-interfering RNA), representing a multifunctional vector system, designed for drug and gene delivery. Apart from polymer design and charge ratio, a more homogeneous complexation could lead to a more uniform charge distribution, subsequently increasing colloidal stability, RNA protection and consequently transfection efficiency. Microfluidic mixing techniques, bringing cationic polymer and nucleic acid together at a constant ratio during the entire mixing process, have the potential for a gentler complexation. In the present study carriers were prepared by a solvent displacement technique. In a first step complex size for addition of RNA during (addition to the aqueous or the organic phase) or after (classical pipetting or microfluidic mixing) carrier assembly was determined by dynamic light scattering. Suitable N/P ratios have previously been selected by measuring size and ζ-potential as a function of N/P. Subsequently, for the most promising techniques (loading after assembly), colloidal stability, the ability to protect RNA as well as transfection efficiency in vitro were compared. Finally, parameters for the superior microfluidic mixing process were optimised with the help of a central composite design. Generally, gentler loading leads to more homogeneous complexes. Hence, possibly due to a more consistent surface coating, loading after carrier assembly resulted in less aggregation. In comparison to bulk mixing, microfluidic assembly exhibited smaller diameters (179±11 vs. 230±97nm), less heterogeneity (PDI=0.205±0.028 vs. 0.353±0.161), enhanced RNA protection (RNA recovery=30.6±1.0 vs. 15.4±1.4%) as well as increased transfection performance (34.8±1.5 vs. 24.5±2.2% knockdown). Therefore, microfluidic complexation represents a reproducible alternative for formulating gene delivery carriers with superior colloidal stability, RNA protection and transfection efficiency.


Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study.
This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.


Use of a hierarchical logistic regression model to determine the impact of war injuries on clinical pregnancy rates in patients undergoing intracytoplasmic sperm injection.
To determine the effects of war injuries, including spinal cord injuries, poisoning, and other injuries, on clinical pregnancy rates in infertile couples undergoing intracytoplasmic sperm injection (ICSI) and to compare the results with infertile couples who were not victims of the war. Retrospective study. A large, national clinic in Tehran, Iran. Six hundred sixty-seven couples undergoing ICSI. Database analysis. Ongoing clinical pregnancy. War victims with spinal cord injuries and those who had been poisoned had the same pregnancy rates as did infertile couples who were not victims of the war. The predictive model shows that the more embryos that are transferred, the more the chances for clinical pregnancies; in addition, the more cycles a couple undergoes, the fewer are the chances for clinical pregnancy in an additional cycle. Finally, younger females have more chances for clinical pregnancy than do older ones. Intracytoplasmic sperm injection is an appropriate option for the treatment of infertile war victim couples, especially for couples suffering from spinal cord injuries and poisoning.


Angiogenesis in arthritis: methodological and analytical details.
Angiogenesis is the formation of new blood vessels from existing vessels. The formation of new vessels appears to be an early and fundamental process for the evolution of the inflammatory response in synovial joints affected by arthritis. The propagation of new vessels in the synovial membrane allows the invasion of this tissue over the intraarticular cartilage in an adherent fashion. This process appears to support the active infiltration of synovial membrane into cartilage and results in erosion and destruction of the cartilage. This process results in joint damage and ultimately in deformity, as the normal joint architecture and balance of tendons becomes disrupted. Angiogenesis may be assessed in vivo by direct visualization through the introduction of a needle arthroscope using local anesthesia, differential patterns of vascular morphology have been described in seropositive rheumatoid arthritis and seronegative arthritides such as psoriatic and reactive arthritis. At a microscopic level, angiogenesis may be examined in the tissue sections using immunohistochemistry or immunofluorescence. Endothelial cells may also be studied in vitro in culture to examine production of angiogenic growth factors, cell activation, migration, and tubule formation. Finally, synovial biopsy explants may be cultured ex vivo to provide a model simulating the intra-articular milieu.


Engineering of Yarrowia lipolytica transporters for high-efficient production of biobased succinic acid from glucose.
Succinic acid (SA) is a crucial metabolic intermediate and platform chemical. Development of biobased processes to achieve sustainable SA production has attracted more and more attention in biotechnology industry. Yarrowia lipolytica has a strong tricarboxylic acid cycle and tolerates low pH conditions, thus making it a potential platform for SA production. However, its SA titers in glucose media remain low. In this study, we screened mitochondrial carriers and C4-dicarboxylic acid transporters to enhance SA secretion in Y. lipolytica. PGC62-SYF-Mae strain with efficient growth and SA production was constructed by optimizing SA biosynthetic pathways and expressing the transporter SpMae1. In fed-batch fermentation, this strain produced 101.4 g/L SA with a productivity of 0.70 g/L/h and a yield of 0.37 g/g glucose, which is the highest SA titer achieved using yeast, with glucose as the sole carbon resource. Our results indicated that transporter engineering is a powerful strategy to achieve the efficient secretion of SA in Y. lipolytica, which will promote the industrial production of bio-based SA.


A mechanism-based potent sirtuin inhibitor containing Nε-thiocarbamoyl-lysine (TuAcK).
In the current study, we have identified N(ε)-thiocarbamoyl-lysine (TuAcK) as a general sirtuin inhibitory warhead which was shown to be able to confer potent sirtuin inhibition. This inhibition was also shown to be mechanism-based in that the TuAck residue was able to be processed by a sirtuin enzyme with the formation of a stalled S-alkylamidate intermediate.


5'-Nucleotidase of cerebellar molecular layer: reduction in Purkinje cell-deficient mutant mice.
The molecular layer of the cerebellar cortex contains high levels of the enzyme 5'-nucleotidase (EC 18.104.22.168), localized predominantly to Bergmann glia. In the present study, histochemical methods have been employed to examine the distribution of cerebellar 5'-nucleotidase in mice of two separate mutant strains in which Purkinje cells are eliminated selectively. In homozygous 'Purkinje cell degeneration' (pcd) and 'nervous' (nr) mice, molecular layer 5'-nucleotidase is greatly reduced and residual enzyme activity in colocalized with surviving Purkinje cells. These results suggest strongly that the expression of 5'-nucleotidase activity by Bergmann glia is under the inductive influence of their associated Purkinje cells.


Roles of age, sex, and weight status in the muscular fitness of Chinese Tibetan children and adolescents living at altitudes over 3600 m: A cross-sectional study.
This study aimed to assess the role of age, sex, and weight status in the development of muscular fitness in a large sample of Chinese Tibetan children and adolescents aged 7-18 years living in areas over 3600 m. A sample of 4673 Chinese Tibetan children and adolescents aged 7-18 years were recruited from 21 schools in three cities (Lhasa, Naqu, and Anduo) of Tibet, China. Grip strength, standing long jump, 30-s sit-ups, and 50-m dash were conducted to determine muscular fitness. Independent sample t tests were conducted to compare muscular fitness between boys and girls for each age group. The changes in mean scores on each muscular fitness test were estimated. The influence of weight status on muscular strength level was also estimated using one-way ANOVA and LSD tests. We also compared the average muscular fitness between Chinese Tibetan and Chinese average level. The muscular fitness of Chinese Tibetan boys aged 7-18 years was higher than that of girls, with older children outperforming younger children. Among the Chinese Tibetan boys, those in the normal-weight group showed the best performance, whereas overweight group showed the best performance among the girls. The performance of Chinese Tibetan children and adolescents in standing long jump and 50-m dash was lower while that in sit-ups was higher than the performance of their Chinese counterparts. Chinese Tibetan children and adolescents have relatively strong abdominal strength, but lower limb strength, which needs to be improved. Age, sex, and weight status should be considered when designing interventions to improve muscular fitness.


Brain enzyme and clinical alterations induced in rats and mice by nitroaliphatic toxicants.
The effects of a single subcutaneous (s.c.) injection of the nitroaliphatic toxicants 3-nitropropanol (NPOH) and 3-nitropropionic acid (NPA) dissolved in physiological saline solution were studied in mice and rats, respectively. Clinical signs observed in both NPOH-treated mice and NPA-treated rats included depression, abnormal motor activity, and recumbency. Succinate dehydrogenase (SDH) activity, demonstrated histochemically in frozen brain sections, was markedly reduced in intoxicated mice and rats. The SDH activity of mitochondrial preparations from brains of intoxicated mice and rats was diminished to 18-24% of control values, although the activity of another mitochondrial flavoprotein enzyme, alpha-glycerophosphate dehydrogenase (alpha-GPDH), was not altered.


Modification of infarct material properties limits adverse ventricular remodeling.
Infarct expansion after myocardial infarction (MI) is an important phenomenon that initiates and sustains adverse left ventricular (LV) remodeling. We tested the hypothesis that infarct modification by material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling. Anteroapical infarction was induced in 21 sheep. Sheep were randomized to injection of saline (2.6 mL) or tissue filler material (2.6 mL) into the infarct within 3 hours of MI. Animals were monitored for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Morphometric measurements were performed of excised hearts to quantify infarct thickness. Regional blood flow was assessed with colored microspheres. Infarct material properties were measured using biaxial tensile testing. Compared with controls at 8 weeks, treatment animals had less infarct expansion, reduced LV dilatation (LV systolic volumes: 60.8±4.3 vs 80.3±6.9 mL; p<0.05), greater ejection fraction (0.310±0.026 vs 0.276±0.013; p<0.05), thicker infarcts (5.5±0.2 vs 2.2±0.3 mm; p<0.05), and greater infarct blood flow (0.22±0.04 vs 0.11±0.03 mL/min/g; p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts. Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection, resulting in the amelioration of infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm.


Phase transformation changes in thermocycled nickel-titanium orthodontic wires.
In the oral environment, orthodontic wires will be subject to thermal fluctuations. The purpose of this study was to investigate the effect of thermocycling on nickel-titanium (NiTi) wire phase transformations. Straight segments from single 27 and 35 degrees C copper NiTi (Ormco), Sentalloy (GAC), and Nitinol Heat Activated (3M Unitek) archwires were sectioned into 5mm segments (n=20). A control group consisted of five randomly selected non-thermocycled segments. The remaining segments were thermocycled between 5 and 55 degrees C with five randomly selected segments analyzed with differential scanning calorimetry (DSC; -100<-->150 degrees C at 10 degrees C/min) after 1000, 5000, and 10,000 cycles. Thermal peaks were evaluated with results analyzed via ANOVA (alpha=0.05). Nitinol HA and Sentalloy did not demonstrate qualitative or quantitative phase transformation behavior differences. Significant differences were observed in some of the copper NiTi transformation temperatures, as well as the heating enthalpy with the 27 degrees C copper NiTi wires (p<0.05). Qualitatively, with increased thermocycling the extent of R-phase in the heating peaks decreased in the 35 degrees C copper NiTi, and an austenite to martensite peak shoulder developed during cooling in the 27 degrees C copper NiTi. Repeated temperature fluctuations may contribute to qualitative and quantitative phase transformation changes in some NiTi wires.


Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization.
The extracellular matrix (ECM) is critical for all aspects of vascular biology. In concert with supporting cells, endothelial cells (ECs) assemble a laminin-rich basement membrane matrix that provides structural and organizational stability. During the onset of angiogenesis, this basement membrane matrix is degraded by proteinases, among which membrane-type matrix metalloproteinases (MT-MMPs) are particularly significant. As angiogenesis proceeds, ECM serves essential functions in supporting key signaling events involved in regulating EC migration, invasion, proliferation, and survival. Moreover, the provisional ECM serves as a pliable scaffold wherein mechanical guidance forces are established among distal ECs, thereby providing organizational cues in the absence of cell-cell contact. Finally, through specific integrin-dependent signal transduction pathways, ECM controls the EC cytoskeleton to orchestrate the complex process of vascular morphogenesis by which proliferating ECs organize into multicellular tubes with functional lumens. Thus, the composition of ECM and therefore the regulation of ECM degradation and remodeling serves pivotally in the control of lumen and tube formation and, finally, neovessel stability and maturation.


Runaway atrioventricular sequential pacemaker after radiation therapy.
Pacemaker malfunction manifested as a runaway circuitry occurred in two patients after they received radiation therapy for treatment of carcinoma. Both pacemakers were programmable atrioventricular sequential units (DVI) with complementary metal oxide semiconductor circuitry. One pacemaker was directly in the radiation field, whereas the other was not directly within the radiation port. Thus, direct irradiation of an implanted pacemaker should be avoided. It is advisable that a pacemaker be shielded even when the pacemaker is not in the direct field of radiation.


Lower Limb Biomechanical Responses During a Standardized Load Carriage Task are Sex Specific.
The purpose of this study was to investigate sex-specific lower limb biomechanical adaptations during a standardized load carriage task in response to a targeted physical training program. Twenty-five healthy civilians (males [n = 13] and females [n = 12]) completed a load carriage task (5 km at 5.5 km·h-1, wearing a 23 kg vest) before and after a 10-week lower-body-focused training program. Kinematics and ground reaction force data were collected during the task and were used to estimate lower limb joint kinematics and kinetics (i.e., moments and powers). Direct statistical comparisons were not conducted due to different data collection protocols between sexes. A two-way repeated measures ANOVA tested for significant interactions between, and main effects of training and distance marched for male and female data, respectively. Primary kinematic and kinetic changes were observed at the knee and ankle joints for males and at the hip and knee joints for females. Knee joint moments increased for both sexes over the 5 km distance marched (P > .05), with males demonstrating significant reductions in peak knee joint extension after training. Hip adduction, internal rotation, and knee internal rotation angles significantly increased after the 5 km load carriage task for females but not males. Differences in adaptive gait strategies between sexes indicate that physical training needs to be tailored to sex-specific requirements to meet standardized load carriage task demands. The findings highlighted previously unfound sex-specific responses that could inform military training and facilitate the integration of female soldiers into physically demanding military roles.


Impact of the Charge Ratio on the In Vivo Immunogenicity of Lipoplexes.
The present study investigated the immunogenic potential of different cationic liposome formulations with a DNA plasmid encoding Pfs25, a malaria transmission-blocking vaccine candidate. Pfs25 plasmid DNA was complexed with cationic liposomes to produce lipoplexes at different charge ratios of the cationic lipid head group to the nucleotide phosphate (N:P). The formation of lipoplexes was visualized by Cryogenic-TEM. Confocal microscopy of lipoplexes formed with GFP encoding plasmid DNA, and flow cytometry was used to determine their in vitro transfection capability. Two different lipoplex formulations using plasmid DNA encoding Pfs25 were evaluated for in vivo immunogenicity after intramuscular administration in Balb/c mice. Immune sera were analyzed by ELISA. The results demonstrated that the cationic liposome-mediated DNA immunization with an N:P charge ratio of 1:3 (anionic lipoplexes) is more effective than the use of naked plasmid DNA alone. No antibody response was observed when lipoplexes with a higher N:P charge ratio of 10:3 (cationic lipoplexes) were used. Trehalose was added to some lipoplex formulations as a cryoprotectant and adjuvant, but it did not yield any further improvement of immunogenicity in vivo. The results suggest that Pfs25 plasmid DNA delivered as lipoplexes at a charge ratio of 1:3 elicited strong immunogenicity in mice and may be improved further to match the immune responses of DNA vaccines administered by in vivo electroporation.


Elevated serum miR-3129-5p contributes to the progression of coronary heart disease via targeting mTOR.
The current study aims to explore the miRNA changes that occur in the serum of patients with coronary heart disease (CHD) and healthy controls using a microarray technique, thereby exploring the potential biomarkers in the diagnosis of CHD and the underlying mechanism. Clinical data were reviewed, and venous blood samples were collected from 66 cases of CHD and 58 cases of healthy controls. MicroRNA-wide expression profiling identified 16 miRNAs that were aberrantly decreased by ~2-fold in the serum of patients with CHD compared to that of healthy controls. RT-PCR analysis indicated that the expression of miR-3129-5p was increased the most in patients with CHD compared with that of controls. Moreover, serum miR-3129-5p was found to be highest in the severe stenosis group, followed by the moderate stenosis group and mild stenosis group. ROC analysis showed that serum miR-3129-5p could differentiate patients with CHD from controls. Further study showed that mTOR was a target gene of miR-3129-5p. Western blot assays demonstrated that miR-3129-5p significantly suppressed the phosphorylation of S6 but increased LC3II/LC3I and Beclin1 levels. Consistently, GFP-LC3 and TEM assays indicated that miR-3129 increased autophagy puncta in H9C2 cells. More importantly, silencing mTOR significantly decreased the expression of p-S6 but increased LC3II/LC3I and Beclin expression even in H9C2 cells transfected with miR-3129-5p inhibitor, indicating that miR-3129-5p-induced cell autophagy was mediated via mTOR in H9C2 cells. In summary, elevated serum miR-3129-5p contributes to CHD by targeting mTOR signaling and may be a therapeutic target in the treatment of CHD.


Evaluating fidelity: predictive validity for a measure of competent adherence to the Oregon model of parent management training.
When efficacious interventions are implemented in real-world conditions, it is important to evaluate whether or not the programs are practiced as intended. This article presents the Fidelity of Implementation Rating System (FIMP), an observation-based measure assessing competent adherence to the Oregon model of Parent Management Training (PMTO). FIMP evaluates 5 dimensions of competent adherence to PMTO (i.e., knowledge, structure, teaching skill, clinical skill, and overall effectiveness) specified in the intervention model. Predictive validity for FIMP was evaluated with a subsample of stepfamilies participating in a preventive PMTO intervention. As hypothesized, high FIMP ratings predicted change in observed parenting practices from baseline to 12 months. The rigor and scope of adherence measures are discussed.


Association of FTO gene variants with adiposity in African-American adolescents.
The prevalence of obesity continues to increase significantly, with the largest rise in the African-American adolescents. Genetic contributions to obesity are being identified with the advent of genome-wide association studies (GWAS). Specifically, variants of the fat mass and obesity associated (FTO) gene have been associated with obesity in populations of European descent. The studies in African Americans have been inconclusive. To further evaluate the association of the FTO gene and adiposity in African Americans, we genotyped 47 single-nucleotide polymorphisms (SNPs), including seven SNPs previously reported to be significant in the literature in a cohort consisting of 561 non-Hispanic white and 497 African-American individuals. Analysis of our data showed 17 SNPs to be associated with BMI Z-score (BMI-Z) in our study population. The strongest association was found in the African Americans. The most significant SNP was rs8057044, which was associated with BMI-Z in the African Americans (P = 0.00054). SNP rs9939609 was found to be significant in the non-Hispanic white population (P = 0.028). Our data confirm the association between FTO and adiposity suggesting that FTO is a childhood obesity susceptibility gene. Our data also identify a novel SNP of the FTO gene (rs8057044) that is associated with measures of adiposity in the African-American population.


Updates on Infection Control in Alternative Health Care Settings.
Patients increasingly receive care from a large spectrum of different settings, placing them at risk for exposure to pathogens by many different sources. Each health care environment has its own specific challenges, and thus infection control programs must be tailored to each specific setting. High-turnover outpatient settings may require additional considerations, such as establishing patient triage and follow-up protocols, and broadened cleaning and disinfection procedures. In nursing homes, infection control programs should focus on surveillance for infections and antimicrobial resistance, outbreak investigation and control plan for epidemics, isolation precautions, hand hygiene, staff education, and employee and resident health programs.


Rosette formation of pig peripheral blood lymphocytes with sheep red blood cells.
Peripheral blood lymphocytes of normal young pigs formed spontaneous and EAC rosettes with sheep red blood cells. Pretreatment of the SRBC with a sulphydryl reagent increased the percentage of spontaneous rosettes and the number of SRBC bound by the lymphocytes. The influence of an incubation period prior to centrifugation and the duration and temperature of the following incubation were tested for spontaneous and EAC rosettes. The importance is stressed to define the number of bound SRBC to call a lymphocyte a "rosette-forming cell". Rosette formation is interpreted as a quantitative rather than a qualitative marker.


Penetration through the peritrophic matrix is a key to lectin toxicity against Tribolium castaneum.
In the last decades lectins have received a lot of attention as potential tools in pest control. Despite substantial progress in the field not all the factors determining insecticidal potency and selectivity of these proteins have been described. Recently, three lectins, RSA (Rhizoctonia solani agglutinin), SNA-I and SNA-II (Sambucus nigra agglutinin I and II) have been shown to be toxic to aphids and caterpillars. In this project we investigated if these lectins are also toxic against larvae and a cell line of the red flour beetle, Tribolium castaneum, a model organism and important pest of stored products. Furthermore, we analyzed the stability of the lectins in the larval gut and used confocal microscopy to compare their efficiency in passing through the peritrophic matrix (PM). We observed that all three lectins were toxic against the T. castaneum cell line and their effectiveness in vitro was in decreasing order SNA-II>SNA-I>RSA with the respective EC50 being 0.1, 0.5 and 3.6 μg/ml. Larvae feeding for 16 day on diets containing 2% RSA, 2% SNA-II and 2% SNA-I weighed 0.14 ± 0.07 mg, 0.67 ± 0.44 mg and 1.89 ± 0.38 mg, corresponding to approximately 7%, 36% and 80% of control larvae, respectively. As a consequence, RSA increased the time to adult emergence by over 3-fold, SNA-II by 1.9-fold and SNA-I by 1.2-fold. RSA and SNA-II were stable in the larval gut, while SNA-I was digested and excreted with the feces. Finally, confocal microscopy confirmed that RSA passed through the PM more efficiently than SNA-II. In conclusion, our data suggest that the lectin ability to pass through the PM, governed by molecule dimensions, charge and size of PM pores, is one of the features that determine the toxicity of these insecticidal proteins.


Pixantrone confers radiosensitization in KRAS mutated cancer cells by suppression of radiation-induced prosurvival pathways.
Radioresistance towards radiation therapy has generated the need for the development of radiosensitizers as a potential drug. KRAS mutation brings radioresistance in tumor cells. The present work proves sensitization of cancer cells towards radiotherapy through inhibition of KRAS activation. Acquiring a drug repurposing approach, the in-silico screening revealed that pixantrone, an antineoplastic drug, possesses a high affinity towards KRAS G12C and G12D subtypes. The SPR study suggests that maximum affinity of pixantrone was observed with KRAS G12C>WT>G12D and G12S. Pixantrone potentially inhibited the KRAS activation in stable transfectants G12C and G12D cell lines and radiosensitized distinct KRAS mutant subtype cells. The combination of pixantrone with radiation causes enhanced dsDNA breaks along with enhanced ATM expression, and increased late apoptosis. The preclinical studies on NCr-fox1nu xenograft mice showed potent inhibition of tumor progression and prolonged survival of mcie due to the radiosensitizing effect of pixantrone. Radiation-induced activation of key effector proteins of RAS downstream pathways, like MAPK and PI3K/Akt/mTOR pathways, were downregulated in tumor cells upon combination treatment. Interestingly, a robust upregulation of senescence marker p21 was observed in the tumor cells in combination treatment. These findings reveal a convergence between KRAS signaling, pixantrone treatment, and radiation conferring tumor cell death.


[Janus kinase inhibitors : Indications, efficacy, uses, what should be taken into account?]
Janus kinase inhibitors (JAKi) represent an immunomodulatory targeted therapy in various dermatoses. Throughout the past few years, JAKi have been approved for atopic dermatitis (AD), psoriasis vulgaris (PSO), alopecia areata (AA), and vitiligo. Further indications are currently under investigation. In this article the various systenic and topical JAKi used in dermatology are being presented regarding their efficacy and safety profile. A specific focus will be set on handling with safety issues including screening and control measures during treatment with JAKi. In addition, future use of JAKi in various dermatological diseases for which nowadays only insufficient therapy options are available is being discussed.


Adsorption of proteins onto glass surfaces and its effect on the intensity of circular dichroism spectra.
Errors in analyzing CD spectra of proteins arising from adsorption loss onto glass surfaces were examined for six proteins: apolipoproteins A-I and E, fibronectin, bovine serum albumin, insulin, and glucagon. Among these, the glycoproteins, apolipoprotein E and fibronectin, adsorbed most onto glass surfaces. Their CD intensities decreased by about 50% when proteins were diluted serially from 1 to 0.01 mg/ml in regular glass-ware and CD was measured in uncoated cells. The other proteins, except glucagon, also showed a certain degree of adsorption. Thus, adsorption loss of proteins onto glass surfaces is common and may lead to serious errors in experimental results. Adsorption can be minimized by using plastic containers and pipet tips, coating the cell with silicone, and wetting the cell before adding the protein solution.


Characterization of Rookie Season Injury and Illness and Career Longevity Among National Basketball Association Players.
There is limited research investigating injury and illness among professional basketball players during their rookie season. By improving the understanding of injury incidence and risk specific to rookie players, sports medicine clinicians may be able to further individualize injury mitigation programs that address the unique needs of rookie players. To compare incidence and rate ratio (RR) of injury and illness among professional National Basketball Association (NBA) players in their rookie season with veteran players and to explore the association of sustaining an injury rookie season with career longevity. This retrospective cohort study used an online data repository and extracted publicly available data about NBA players between the 2007 and 2008 season to the 2018 and 2019 season. Available data for initial injury and all subsequent injuries were extracted during this time frame. Injury and illness based on injury status during the rookie season of professional NBA players. Injury and illness incidence and RR. Association of injury during the rookie season with career longevity was assessed via Poisson regressions. Of the 12 basketball seasons analyzed, 904 NBA players were included (mean [SD] age, 24.6 [3.9] years; body mass index, 24.8 [1.8]). The injury and illness incidence for rookie players was 14.28 per 1000 athlete game exposures (AGEs). Among all body regions, ankle injuries had the greatest injury incidence among players injured during their rookie season (3.17 [95% CI, 3.15-3.19] per 1000 AGEs). Rookie athletes demonstrated higher RR compared with veterans across multiple regions of the body (ankle: 1.32; 95% CI, 1.12 to 1.52; foot/toe: 1.29; 95% CI, 0.97 to 1.61; shoulder/arm/elbow: 1.43; 95% CI, 1.10 to 1.77; head/neck: 1.21; 95% CI, 0.61 to 1.81; concussions: 2.39; 95% CI, 1.89 to 2.90; illness: 1.14; 95% CI, 0.87 to 1.40), and demonstrated a higher rate of initial injuries compared with veteran players (1.41; 95% CI, 1.29 to 1.53). Players who sustained an injury rookie season demonstrated an unadjusted decrease in total seasons played (-0.4 [95% CI, -0.5 to -0.3] log years; P < .001), but this decrease was not observed within adjusted analysis (0.1 [95% CI, -0.1 to 0.2] log years; P = .36). In this study, rookie athletes demonstrated the highest injury incidence at the ankle and increased RR across multiple regions. These findings may reflect differences in preseason conditioning or load variables impacting rookie athletes and warrant further investigation. Future research is needed to determine the association of cumulative injury burden vs a singular injury event on career longevity.


Inhibition of Tumor Growth and Sensitization to Sunitinib by RNA Interference Targeting Programmed Death-ligand 1 in Mouse Renal Cell Carcinoma RenCa Model.
There are several unresolved issues regarding the combined treatment with an immune checkpoint inhibitor and anti-angiogenic agent for renal cell carcinoma (RCC) patients. The purpose of this study was to address the inhibitory effects of programmed death-ligand 1 (PD-L1) expression on growth and sensitivity to sunitinib in the mouse RCC RenCa model. We established RenCa/sh-PD-L1 by transfecting RenCa cells with a plasmid carrying a short hairpin RNA targeted against PD-L1. The growth pattern of RenCa/sh-PD-L1 with or without sunitinib was compared to that of RenCa cells transfected with control plasmid alone (RenCa/Co). No significant difference in growth or sensitivity to sinitinib was noted between RenCa/sh-PD-L1 and RenCa/Co cells in vitro. The tumor volume in mice subcutaneously injected with RenCa/sh-PD-L1 was significantly smaller than that with RenCa/Co. Treatment of mice bearing each tumor with sunitinib resulted in a significant reduction of the RenCa/sh-PD-L1 tumor compared to the RenCa/Co tumor. Moreover, infiltration by CD8+ T cells of RenCa/sh-PD-L1 tumors was significantly higher than that of RenCa/Co tumors, irrespective of treatment with sunitinib. Suppressed expression of PD-L1 could increase tumor-infiltrating CD8+ T cells and result in growth inhibition as well as enhanced sensitivity to sunitinib in the RenCa model.