Morphology and distribution of serotoninergic and oculomotor internuclear neurons in the cat midbrain.
Serotoninergic fibers have been reported in both the abducens and facial nuclei of the cat. Furthermore, serotoninergic dorsal raphe and oculomotor internuclear neurons occupy similar locations in the periaqueductal gray overlying the oculomotor and trochlear motor nuclei. To resolve the issue of whether these two populations of neurons overlap, serotoninergic fibers were assayed in the abducens and facial nucleus; then the morphologies and distributions of identified serotoninergic neurons and oculomotor internuclear neurons were determined. Both the abducens and facial nuclei contained varicosities labelled with antibody to serotonin, but a much higher density of immunoreactive fibers was present in the latter, especially in its medial aspect. Distinct synaptic profiles labelled with antibodies to serotonin were observed in both nuclei. In both cases, terminal profiles contained numerous small, predominantly spheroidal, synaptic vesicles as well as a few, large, dense-core vesicles. These profiles made synaptic contacts onto dendritic and, in the facial nucleus, somatic profiles that occasionally displayed asymmetric, postsynaptic, membrane densifications. Following injection of horseradish peroxidase into either the abducens or facial nuclei, double-label immunohistochemical techniques demonstrated that the serotoninergic and oculomotor internuclear neurons form two distinct cell populations. The immunoreactive serotoninergic cells were distributed within the dorsal raphe nucleus, predominantly caudal to the retrogradely labelled oculomotor internuclear neurons. The latter were located in the oculomotor nucleus along its dorsal border and in the adjacent supraoculomotor area. Intracellular injection of horseradish peroxidase revealed that oculomotor internuclear neurons have multipolar somata with up to ten long, tapering dendrites that bifurcate approximately five times. Their dendritic fields were generally contained within the nucleus and adjacent supraoculomotor area. In contrast, putative serotoninergic neurons were often spindle-shaped and exhibited far fewer primary dendrites. Many of these long, narrow, sparsely branched dendrites crossed the midline and extended to the surface of the cerebral aqueduct. In the vicinity of the aqueduct they branched repeatedly to form a dendritic thicket. The axons of the intracellularly stained serotoninergic neurons emerged either from the somata or the end of a process with dendritic morphology, and in some cases they produced axon collaterals within the periaqueductal gray. Thus the oculomotor internuclear and serotoninergic populations differ in both distribution and morphology.(ABSTRACT TRUNCATED AT 400 WORDS)


Genomic analysis of facultatively oligotrophic haloarchaea of the genera Halarchaeum, Halorubrum, and Halolamina, isolated from solar salt.
Extremely halophilic archaea (haloarchaea) belonging to the phylum Euryarchaeota have been found in high-salinity environments. In this study, Halarchaeum sp. CBA1220, Halorubrum sp. CBA1229, and Halolamina sp. CBA1230, which are facultatively oligotrophic haloarchaea, were isolated from solar salt by culture under oligotrophic culture conditions. The complete genomes of strains CBA1220, CBA1229, and CBA1230 were sequenced and were found to contain 3,175,875, 3,582,278, and 3,465,332 bp, with a G + C content of 68.25, 67.66, and 66.75 mol %, respectively. In total, 60, 36, and 33 carbohydrate-active enzyme genes were determined in the respective strains. The strains harbored various genes encoding stress-tolerance proteins, including universal stress proteins, cold-shock proteins, and rubrerythrin and rubrerythrin-related proteins. The genome data produced in this study will facilitate further research to improve our understanding of other halophilic strains and promote their industrial application.


A fluorometric study of the interaction of bradykinin with lipids.
The interaction of bradykinin (BK) with lipids has been followed by steady-state fluorescence measurements. Addition of either cerebroside sulfate (CS) or phosphatidylinositol (PI), solubilized with the nonionic surfactant C12E8, to BK or its analogue [Gly6]-BK enhances the relative fluorescence intensity of peptide emission at 288 nm. Fluorometric titration of the peptide with lipid has been used to quantitate the interactions in terms of stoichiometry and equilibrium constant. Job's method of continuous variation for the BK-CS interaction gave a stoichiometry of 1:2 for the complex. The value of the equilibrium constant, K, for the interaction of either BK or [Gly6]-BK with CS is 1.5.10(4) M-1. The BK-PI interaction is weaker; K = 5.0.10(3) M-1. Although electrostatic forces no doubt play a major role in these interactions, measurements on the model peptide Gly-Phe-Gly indicate that the phenylalanine residues of BK are disposed in the hydrophobic environment provided by the lipid-C12E8 mixed micelle. 13C-NMR measurements on [99% 13C alpha-Gly6]-BK show that there is no change in its cis/trans ratio upon interaction with CS. The increase in the relative fluorescence intensity of BK accompanying its cooperative interaction with sodium dodecyl sulfate (SDS) implicates the role of hydrophobic forces in this interaction as well. These results bear on the interpretation of the changes in circular dichroism (CD) of BK caused by SDS.


Opisthorchis viverrini: an underestimated parasite in world health.
Infection with Opisthorchis viverrini and its associated cholangiocarcinoma (CCA) is an underestimated problem in the Mekong region of Southeast Asia, despite the widespread use of praziquantel and health education measures for parasite control. Although data from Cambodia, Laos and Vietnam are rare, data from Thailand often show wide-ranging variability in epidemiological parameters, including human morbidity and the prevalence and incidence of CCA. The recent discovery of high levels of population genetic variability in O. viverrini in different wetlands in Thailand and Laos, which indicates the presence of sibling species, suggests that we have underestimated the complexity of this epidemiological situation. Future research should determine the relationship between the genetic variability of O. viverrini and patterns of opisthorchiasis-related disease.


Prognostic capacity of Systemic Inflammation Response Index (SIRI) in patients with head and neck squamous cell carcinoma.
Inflammation and immune evasion are associated with carcinogenesis. Systemic Inflammation Response Index (SIRI) has been proposed as a pretreatment peripheral blood biomarker. The aim of this study is to analyze its prognostic capacity in head and neck squamous cell carcinomas (HNSCC). We performed a retrospective study in 824 patients with HNSCC. SIRI was calculated by neutrophils*monocytes/lymphocytes. Using a recursive-partitioning analysis considering disease-specific survival (DSS) as dependent variable, three categories were defined according to SIRI value. Males, patients with history of toxic consumption, oropharyngeal or hypopharyngeal tumors, and advanced tumors had a significantly higher SIRI value. As SIRI increased, a significant decrease in DSS was observed. In a multivariable analysis, SIRI was an independent predictor of DSS. Moreover, SIRI was a significant predictor of local, regional, and distant recurrence-free survival. SIRI has independent prognostic capacity in HNSCC. Patients with higher SIRI have a significant decrease in DSS.


[Topics of occupational medicine and environment in codes and social accountability standards of business].
The problems of social accountability as applied to the occupational safety, health and environment are discussed. Russian and international codes and standards in the field are reviewed. Legal duties and rights of employers in occupational risk management for workers' health are considered. Some ethical aspects including health protection of female workers are discussed.


Acetylcholine in human CSF: methodological considerations and levels in dementia of Alzheimer type.
Four different methods to measure acetylcholine (ACh) and choline (Ch) concentration, i.e. thermospray/mass spectroscopy (TS/MS), high pressure liquid chromatography/mass spectroscopy (HPLC/MS), high pressure liquid chromatography/electrochemical detection (HPLC/ECD) and gas chromatography/mass spectroscopy (GC/MS), both latter methods coupled to a solid phase extraction system were compared for their applicability to human lumbar cerebrospinal fluid (CSF). Furthermore, samples from 15 control persons and 11 patients with dementia of Alzheimer-type (DAT) were compared to search for an ACh deficit in the CSF in DAT. GC/MS was the most sensitive, but most laborious method, and HPLC/ECD was acceptably sensitive, reliable and more specific. TS/MS was not specific enough for CSF extracts and HPLC/MS was more specific, but far less sensitive. Thus, only GC/MS and HPLC/ECD were qualified to detect ACh in human CSF extracts. Comparison of GC/MS and HPLC/ECD revealed highly correlated levels of ACh (r = 0.999). Using HPLC/ECD, ACh concentrations were greatly reduced in the DAT group (3.75 +/- 1.40 pmol/ml CSF) as compared to the controls (6.14 +/- 1.39 pmol/ml CSF), but the difference between controls and DAT patients was not statistically significant due to the number of samples below detection limit (8 out of 11 samples in DAT, 7 out of 15 in controls). Ch concentrations were not statistically significant between the two groups. The data show that methodological limitations preclude a widespread clinical application of determining ACh in the human CSF. Despite of reductions of ACh in the CSF in DAT, the determination of Ach in the CSF is not suitable for diagnostic purposes.


Volar/dorsal compressive mechanical behavior of the transverse carpal ligament.
Mechanical insult to the median nerve caused by contact with the digital flexor tendons and/or carpal tunnel boundaries may contribute to the development of carpal tunnel syndrome. Since the transverse carpal ligament (TCL) comprises the volar boundary of the carpal tunnel, its mechanics in part govern the potential insult to the median nerve. Using unconfined compression testing in combination with a finite element-based optimization process, nominal stiffness measurements and first-order Ogden hyperelastic material coefficients (μ and α ) were determined to describe the volar/dorsal compressive behavior of the TCL. Five different locations on the TCL were tested, three of which were deep to the origins of the thenar and hypothenar muscles. The average (± standard deviation) low-strain and high-strain TCL stiffness values in compression sites outside the muscle attachment region were 3.6 N/mm (±2.7) and 28.0 N/mm (±20.2), respectively. The average stiffness values at compression sites with muscle attachments were notably lower, with low-strain and high-strain stiffness values of 1.2 N/mm (±0.5) and 9.7 N/mm (±4.8), respectively. The average Ogden coefficients for the muscle attachment region were 51.6 kPa (±16.5) for μ and 16.5 (±2.0) for α, while coefficients for the non-muscle attachment region were 117.8 kPa (±86.8) for μ and 17.2 (±1.6) for α. These TCL compressive mechanical properties can help inprove computational models, which can be used to provide insight into the mechanisms of median nerve injury leading to the onset of carpal tunnel syndrome symptoms.


Comparison of sensory integration and operant methods for production of vocalization in profoundly retarded adults.
Sensory integration, operant and combined therapies were used with 27 profoundly retarded, marginally vocal clients. The sensory integration and combined methods yielded significant increases in rate of vocalizations. The operant techniques also increased rate of vocalizations but the gains were more variable than for the sensory integration procedure and they were positively and highly correlated with pretest rates of vocalization. It appears that sensory integration methods can be an effective method for elicting vocalizations when such behaviors are too infrequent for operant techniques.


Cyclosporine A induces testicular injury via mitochondrial apoptotic pathway by regulation of mir-34a and sirt-1 in male rats: The rescue effect of curcumin.
Testicular damage contributes to cyclosporine A (CsA) induced male infertility. However, the exact underlying molecular mediators involved in CsA-induced testis disorder remains unclear. The present study aimed to characterize the role of mir-34a/sirt-1 in CsA induced testicular injury alone or in combination with curcumin. A total of twenty-eight male Wistar rats were subdivided into four groups: control (Con), sham, cyclosporine A (CsA), cyclosporineA + curcumin (CsA + cur). The animals received cyclosporine A (30 mg/kg) and curcumin (40 mg/kg) for 28 days by oral gavage. At the end of the experiment, CsA administration significantly resulted in a decrease in testis weight and testis coefficient. The molecular analysis demonstrated that CsA exposure increased 8-OHdg and Nox4 protein contents in the testis tissue. TUNEL staining indicated that CsA caused the number of apoptotic cells to increase in the testes of male rats. In addition, exposure to CsA resulted in an increased expression of Bax, and a decreased expresion in that of Bcl-2, with a concomitant up-regulation of the Bax/Bcl-2, c-Caspase-3/p-Caspase-3 ratio and cytochrome c level. Meanwhile, exposure to CsA increased the expression of mir-34a and decreased sirt-1 protein level in the testis tissue samples compared to the control group. Taken together, our findings suggested that CsA can cause damage to testicular germ cells via oxidative stress and mitochondrial apoptotic pathway, and probably mir-34a/sirt-1 play a crucial role in this process. It also demonstrates that these negative effects of CsA can be reduced by using curcumin as an antioxidant and anti-inflammatory agent.


Would modulation of intracellular Ca2+ be antiarrhythmic?
Under several types of conditions, reversal of steps of excitation-contraction coupling (RECC) can give rise to nondriven electrical activity. In this review we explore those conditions for several cardiac cell types (SA, atrial, Purkinje, ventricular cells). We find that abnormal spontaneous Ca2+ release from intracellular Ca2+ stores, aberrant Ca2+ influx from sarcolemmal channels or abnormal Ca2+ surges in nonuniform muscle can be the initiators of the RECC. Often, with such increases in Ca2+, spontaneous Ca2+ waves occur and lead to membrane depolarizations. Because the change in membrane voltage is produced by Ca2+-dependent changes in ion channel function, we also review here what is known about the molecular interaction of Ca2+ and several Ca2+-dependent processes, including the intracellular Ca2+ release channels implicated in the genetic basis of some forms of human arrhythmias. Finally, we review what is known about the effectiveness of several agents in modifying such Ca2+-dependent arrhythmias.


Bladder Hamartoma in a Fetus: Case Report.
We present the case of the youngest reported patient with a bladder hamartoma detected prenatally by ultrasonography. Bladder tumors in newborns are rare, but a hamartoma should not be discarded among the diagnostic possibilities when evaluating a fetus or a newborn with a polypoid bladder lesion.


Non-coding RNA LINC00473 mediates decidualization of human endometrial stromal cells in response to cAMP signaling.
Decidualization is an essential step in the establishment of pregnancy. However, the functional contributions of long intergenic noncoding RNAs (LincRNAs) to decidualization have not been explored. To explore the regulation and role of LincRNAs during human decidualization, human endometrial stromal cells (HESCs) are induced to undergo in vitro decidualization by treating with estradiol-17β, db-cAMP and medroxyprogesterone acetate. LINC00473 (LINC473) expression is highly induced in HESCs after decidual stimulus. We found that cAMP-PKA pathway regulates the expression of LINC473 through IL-11-mediated STAT3 phosphorylation. RNA interference-mediated down-regulation of LINC473 inhibits in vitro decidualization. These results suggested that LINC473 might be functionally required for human decidualization. This is the first report demonstrating the presence of LincRNA during human decidualization.


Transcriptome sequencing, annotation and expression analysis of Nannochloropsis sp. at different growth phases.
Nannochloropsis sp. is an oil-rich microalga. The lipid content of cells at stationary growth phase was much higher than that of cells at logarithm growth phase, but very little information focusing on the abundances of gene transcripts concerning lipid accumulation is available. In present study, the second generation Illumina sequencing was used to investigate the genes and pathways of Nannochloropsis sp. in order to identify those involved in lipid metabolism. In total, 29,203 unigenes were obtained from logarithm and stationary growth phases. The transcripts of some unigenes were differentially abundant at two growth phases. Among the unigenes obtained, about 195 unigenes were involved in lipid metabolism and 315 unigenes were putatively transcription factors. These genes are a very useful resource for the future studies of Nannochloropsis sp.


The Bergen 4-day treatment for panic disorder: adapting to COVID-19 restrictions with a hybrid approach of face-to-face and videoconference modalities.
The Bergen 4-day treatment (B4DT) is a concentrated exposure-based therapy that has been shown to be effective in the treatment of anxiety disorders. The current study sought to examine the effectiveness of B4DT for panic disorder (PD), when delivered with a combination of face-to-face sessions and videoconferencing. Treatment was delivered to 50 patients from April 2020 to May 2021. Because of regulations during the pandemic, a significant portion of the treatment was conducted via videoconference. The primary outcome measure was the clinician-rated Panic Disorder Severity Scale (PDSS), and secondary measures included patient-rated symptoms of panic disorder, agoraphobia, generalized anxiety, depression, and treatment satisfaction. Changes in symptom levels over time were estimated using multilevel models. Patients showed a significant reduction in clinician-rated symptoms of panic disorder (Measured by PDSS) from before treatment to post treatment (d = 2.18) and 3-month follow-up (d = 2.01). At three months follow-up 62% of patients were classified as in remission, while 70% reported a clinically significant response. We also found a reduction in symptoms of depression and generalized anxiety, and the patients reported high satisfaction with the treatment. The current study suggests that B4DT delivered in a combination of videoconference and face-to-face meetings may be a useful treatment approach. As the study is uncontrolled, future studies should also include more strictly designed investigations.


InAs/Si Hetero-Junction Nanotube Tunnel Transistors.
Hetero-structure tunnel junctions in non-planar gate-all-around nanowire (GAA NW) tunnel FETs (TFETs) have shown significant enhancement in 'ON' state tunnel current over their all-silicon counterpart. Here we show the unique concept of nanotube TFET in a hetero-structure configuration that is capable of much higher drive current as opposed to that of GAA NW TFETs.Through the use of inner/outer core-shell gates, a single III-V hetero-structured nanotube TFET leverages physically larger tunneling area while achieving higher driver current (ION) and saving real estates by eliminating arraying requirement. Numerical simulations has shown that a 10 nm thin nanotube TFET with a 100 nm core gate has a 5×normalized output current compared to a 10 nm diameter GAA NW TFET.


Computer assisted leukocyte adhesion measurement in intravital microscopy.
The pathogenetic role of the leukocytes in the development of postischemic injury is not yet understood. Therefore a model was developed which allows for in vivo quantification of leukocyte-endothelium interaction in the awake animal. The velocity of leukocytes was measured by means of intravital microscopy and interactive digital image analysis. An adhesion coefficient (AC) was calculated which characterizes the degree of the leukocyte-endothelium interaction. A special procedure of automatically taking image samples for the leukocyte velocity measurement reduces observer bias. As shown in a validation experiment, this procedure yields reproducible results and therefore allows to quantify the influence of prophylactic and therapeutic measures on postischemic leukocyte-endothelium interaction.


Intravenous Administration of Heat Shock-Treated MSCs Can Improve Neuroprotection and Neuroregeneration in Canine Spinal Cord Injury Model.
Transplantation of mesenchymal stem cells (MSCs) is a promising treatment for spinal cord injury (SCI). However, many transplanted cells die within a few days, eventually limiting the efficacy of cellular therapy. To overcome this problem, we focused on the potential of heat shock (HS) proteins in facilitating recovery from cell damage and protecting against cytotoxicity. PCR results showed that the expression of neurotrophic factor, anti-inflammatory, stemness, and homing genes increased in HS-treated MSCs. We investigated whether HS-treated MSCs could promote recovery of hindlimb function in an acute canine SCI model. We compared the effects of intravenous transplantation with (i) lactated Ringer's solution as a control, (ii) green fluorescent protein-expressing MSCs (MSCs-GFP), and (iii) GFP-expressing and HS-treated MSCs (MSCs-GFP-HS). Spinal cords were harvested at four weeks and used for Western blot and histopathological analyses. The MSCs-GFP-HS group showed significant improvements in hindlimb function from weeks 3 and 4 compared with the other groups. This group also showed higher expression of neural markers, fewer intervening fibrotic changes, and pronounced myelination. These results suggest that induction of an HS response in MSCs could promote neural sparing. In conclusion, transplantation of HS-treated MSCs could improve neuroprotection and neuroregeneration in acute SCI.


Further studies and biological activities of macromolecular protein R-Phycoerythrin from Portieria hornemannii.
In the present study, the purified R-Phycoerythrin (R-PE) from a red alga Portieria hornemannii was subjected to the analysis of stability under the influence of different agents. Among the various inhibitors tested on R-PE EDTA at lower concentrations (<1 mM) supported the activity of R-PE. When R-PE was exposed to different organic solvents, ethanol supported the activity at the maximum followed by acetone, ethyl acetate, chloroform and methanol. Citric acid, as a preservative maintained the stability of R-PE both under 0 ± 5 °C and 30 ± 5 °C with 59.34% and 56.23% respectively, on 30th day. Thermal decomposition of the R-PE began near 60 °C. Maximum weight loss was occurred between 150 °C and 500 °C. Complete weight loss was recorded around 875 °C. Thermal denaturation was observed between 19 °C and 40 °C. Moderate to low antioxidant activities were observed in R-PE in relation to total antioxidant activities. After characterization, R-PE was taken for in vitro anticancer studies against selected cancer cell lines. Further studies involving AO/EB fluorescence staining and phase contrast microscope revealed characteristic apoptotic features like cell shrinkage, membrane blebbing, and nuclear DNA fragmentation, etc. Likewise, FACS analysis revealed the cell cycle distribution pattern of A549 and HepG2 cells.


Topical cardiac hypothermia for myocardial preservation.
We compared moderate (29 degrees C.) and profound (5 degrees C.) (ice chips) cardiac hypothermia for myocardial preservation during aortic cross-clamping for 30 or 60 minutes in a canine right heart bypass preparation. Ventricular function deteriorated significantly at 29 degrees C. but not at 5 degrees C. Maximum dp/dt declined only after 60 minutes of ischemia at 29 degrees C., and Vmax decreased after one hour at either temperature. Lactate and pyruvate washout were greater after 29 degrees C., and pyruvate production persisted after 60 minutes of ischemia at 29 degrees C. Reactive hyperemia was greater after 30 minutes of ischemia at 29 degrees C. Reactive hyperemia was greater after 30 minutes of ischemia at 29 degrees C., and total coronary flow remained elevated after 60 minutes of ischemia at 29 degrees C. Coronary flow distribution was not altered by hypothermia. Ultrastructural changes were primarily time dependent and not temperature dependent. Ice-induced subepicardial injury was not evident in the ultrastructure or by flow distribution. Sixty minutes of profound topical cardiac hypothermia is moderately well tolerated by the canine heart, but functional and structural alterations are evident.


Effects of raw and diluted municipal sewage effluent with micronutrient foliar sprays on the growth and nutrient concentration of foxtail millet in southeast Iran.
In this study, the effect of irrigation with raw or diluted municipal sewage effluent accompanied by foliar micronutrient fertilizer sprays was examined on the growth, dry matter accumulation, grain yield, and mineral nutrients in foxtail millet plants. The experimental design was a split plot with three irrigation sources: raw sewage, 50% diluted sewage, and well water comprising the main treatments, and four combinations of Mn and Zn foliar sprays as sub-treatments that were applied with four replications. The experiment was conducted in 2009 at the Zabol University research farm in Zabol, south Iran. The applied municipal sewage effluent contained higher levels of micronutrients and macronutrients and exhibited greater degrees of electrical conductivity compared to well water. Because of the small scale of industrial activities in Zabol, the amount of heavy metals in the sewage was negligible (below the limits set for irrigation water in agricultural lands); these contaminants would not be severely detrimental to crop growth. The experimental results indicated that irrigation of plants with raw or diluted sewage stimulates the measured growth and productivity parameters of foxtail millet plants. The concentrations of micronutrients and macronutrients were also positively affected. These stimulations were attributed to the presence of high levels of such essential nutrients as N, P, and organic matter in wastewater. Supplied in sewage water alone, Mn and Zn were not able to raise the productivity of millet to the level obtained using fertilizers at the recommended values; this by itself indicated that additional nutrients from fertilizers are required to obtain higher levels of millet productivity with sewage farming. Despite the differences in nutrient concentrations among the different irrigation water sources, the micronutrient foliar sprays did not affect the concentrations of micronutrients and macronutrients in foxtail millet plants. These results suggested that municipal sewage effluent could be utilized efficiently as an important source of water, and that the nutrients used in growing foxtail millet with sewage water irrigation did not have any significant harmful effect on crop productivity. In contrast, the nutrients proved beneficial to soil fertility and millet productivity and quality.


Extracellular vesicles in cardiovascular diseases.
Due to the continued high incidence and mortality rate worldwide, there is still a need to develop new strategies for the prevention, diagnosis and treatment of cardiovascular diseases (CVDs). Proper cardiovascular function depends on the coordinated interplay and communication between cardiomyocytes and noncardiomyocytes. Extracellular vesicles (EVs) are enclosed in a lipid bilayer and represent a significant mechanism for intracellular communication. By containing and transporting various bioactive molecules, such as micro-ribonucleic acids (miRs) and proteins, to target cells, EVs impart favourable, neutral or detrimental effects on recipient cells, such as modulating gene expression, influencing cell phenotype, affecting molecular pathways and mediating biological behaviours. EVs can be released by cardiovascular system-related cells, such as cardiomyocytes, endotheliocytes, fibroblasts, platelets, smooth muscle cells, leucocytes, monocytes and macrophages. EVs containing miRs and proteins regulate a multitude of diverse functions in target cells, maintaining cardiovascular balance and health or inducing pathological changes in CVDs. On the one hand, miRs and proteins transferred by EVs play biological roles in maintaining normal cardiac structure and function under physiological conditions. On the other hand, EVs change the composition of their miR and protein cargoes under pathological conditions, which gives rise to the development of CVDs. Therefore, EVs hold tremendous potential to prevent, diagnose and treat CVDs. The current article reviews the specific functions of EVs in different CVDs.


Qualitative and quantitative comparison of amounts of narrowing by atherosclerotic plaques in the major epicardial coronary arteries at necropsy in sudden coronary death, transmural acute myocardial infarction, transmural healed myocardial infarction and unstable angina pectoris.
The amounts of narrowing of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries by atherosclerotic plaques were compared in 4 subsets of coronary patients. Of the 129 patients studied at necropsy, an average of 2.7 of the 4 arteries was narrowed greater than 75% in cross-sectional area at some point (0.7/4 in controls), and the group with unstable angina pectoris (3.2/4) had more narrowing than did the groups with sudden coronary death (2.8/4), acute myocardial infarction (2.7/4) and healed myocardial infarction (2.3/4). Each of the 4 major epicardial coronary arteries was divided into 5-mm long segments and a histologic section was prepared and stained by the Movat method of each of the 6,461 segments in the 129 patients and in the 1,849 segments in the 40 control subjects. In the 129 patients, 35% of the 5-mm segments were narrowed 75 to 100% in cross-sectional area (3% in controls) and the group with unstable angina had the highest percent (48%) of segments severely narrowed compared to the groups with sudden coronary death (36%), acute myocardial infarction (34%) and healed myocardial infarction (31%). Thus, of the 4 subsets of patients with fatal coronary artery disease studied at necropsy, those with unstable angina pectoris had the most severe and extensive coronary atherosclerosis.


The effects of coumarin and suramin on the growth of malignant renal and prostatic cell lines.
Coumarin is known to exert an anti-neoplastic action in patients with malignant melanoma and renal cell carcinoma. We examined the effects of various concentrations (0, 10, 50, 100, 250, 500 micrograms/ml) of coumarin on the proliferation of two renal cell carcinoma cell lines (786-O and A-498) and two malignant prostatic cell lines (DU145 and LNCaP). After 5 days of treatment, coumarin inhibited the growth of the four cell lines. The LNCaP prostatic cell line was more sensitive than the other cell lines to the inhibitory effects of coumarin. We also examined the effects of various concentrations of suramin (0, 50, 200 and 400 micrograms/ml), and anti-neoplastic compound currently undergoing clinical trials, on the growth of the 786-O and LNCaP cell lines. Both of these were inhibited by suramin at concentrations greater than 100 micrograms/ml. Finally we examined the effects of combined treatment with coumarin and suramin on the growth of LNCaP and 786-O cells. When combined with all concentrations of suramin studied (0, 50, 200 and 400 micrograms/ml), coumarin further inhibited cellular proliferation of the LNCaP and 786-O cell lines. However, the combination of the highest concentration of coumarin (500 micrograms/ml) with suramin at 400 micrograms/ml did not inhibit the proliferation of the cells more than 500 micrograms/ml coumarin alone.


Integrated cytogenetic map of mitotic metaphase chromosome 9 of maize: resolution, sensitivity, and banding paint development.
To study the correlation of the sequence positions on the physical DNA finger print contig (FPC) map and cytogenetic maps of pachytene and somatic maize chromosomes, sequences located along the chromosome 9 FPC map approximately every 10 Mb were selected to place on maize chromosomes using fluorescent in situ hybridization (FISH). The probes were produced as pooled polymerase chain reaction products based on sequences of genetic markers or repeat-free portions of mapped bacterial artificial chromosome (BAC) clones. Fifteen probes were visualized on chromosome 9. The cytological positions of most sequences correspond on the pachytene, somatic, and FPC maps except some probes at the pericentromeric regions. Because of unequal condensation of mitotic metaphase chromosomes, being lower at pericentromeric regions and higher in the arms, probe positions are displaced to the distal ends of both arms. The axial resolution of FISH on somatic chromosome 9 varied from 3.3 to 8.2 Mb, which is 12-30 times lower than on pachytene chromosomes. The probe collection can be used as chromosomal landmarks or as a "banding paint" for the physical mapping of sequences including transgenes and BAC clones and for studying chromosomal rearrangements.


A rare case of squamous cell carcinoma of the lung harbouring ALK and BRAF activating mutations.
The management of non-small cell lung cancer has significantly changed over the past few years through greater understanding of tumour biology. The identification of activating mutations has led to the development of targeted agents. Coexisting mutations in non-small cell lung cancer is uncommon, particularly in squamous cell carcinoma. Our case represents a late gentleman with squamous cell carcinoma of the lung with both a BRAF mutation and ALK rearrangement prior to treatment.


Fertility and pregnancy in Iranian thalassemia patients: An update on transfusion complications.
Despite the significant advances in thalassemia pathobiology and efficacy of chelation regimens, complications of transfusion therapy have attenuated the reproductive health of thalassemia patients. Depending on clinical profiles, we aimed to assess the fertility status and stresses among thalassemia patients who desired to have children. A total of 213 couples in reproductive ages were enrolled in this study in Tehran. Patients' demographic, clinical, fertility and spouse's health status were documented. We evaluated the pituitary-gonadal axis, serum ferritin, liver enzymes, and alloimmunization before planning a pregnancy and reported them as a function of spontaneous conception and transfusion dependency. Data showed that 131 patients (62%) had 228 spontaneous pregnancies leading to 198 (86.6%) successful pregnancies. A significant difference was observed in spontaneous pregnancy with respect to fertility complications and transfusion dependency. In addition, the clinical conditions of spouses in patients with any spontaneous pregnancy were more thalassemia carriers (P < .05). Moreover, serum ferritin levels had a significant negative correlation with the levels of Testosterone, Estradiol, luteinizing hormone, and follicle-stimulating hormone. Furthermore, a significant positive correlation was reported with the level of liver enzymes. Finally, alanine transaminase and aspartate transaminase had a significant negative correlation with pituitary hormones. We suggest that organised instruction in addition to good iron chelation, especially during the puberty period, would reduce the oxidative damage and related complications in thalassemia patients. Moreover, infertility seems to be attributed to iron deposition in various endocrine organs, pituitary, reproductive system and the liver, contributing to hormonal metabolism.


Deaf children can learn to hear.
For more than thirty years the author has been using the "unisensory" approach to work with hearing-impaired children, having learned the principles from her teacher, Emil Froeschels. The approach is based on the theory that even minimal amounts of residual hearing in a hearing-impaired infant, if stimulated in a unisensory fashion, could lead to the development of spontaneous speech and oral communication. Children taught by this method learn to process language through their amplified hearing. They acquire language that is adequate for them to be mainstreamed with their hearing peers from the beginning. The article describes seven requisites to an effective unisensory approach.


Humoral immune response against antigen 60 in BCG-vaccinated infants.
An ELISA assay based on the A-60 antigen complex from Mycobacterium bovis BCG cytoplasm was used to detect anti-mycobacterial antibodies of different classes in the sera of 63 BCG-vaccinated infants during the 6-month post-vaccination period. The mean IgM and IgA levels increased, whereas the mean IgG level decreased after BCG vaccination. However, in a minority of cases only Ig levels were above the cut-off line: this was true for IgM in 11/63 (17%) cases and for IgA in 14/63 (22%) of cases but none of the tested infants was anti-A60 IgG ELISA positive. Fifty-two infants (83%) were tuberculin-positive eight weeks after vaccination, and no significant difference in mean antibody levels of tuberculin-positive and negative cases was observed, except for IgG (p < 0.05).


Antibody-mediated rejection: hyperacute rejection reality in liver transplantation? A case report.
Hyperacute rejection is rare among ABO-compatible liver transplantations. The mechanism is donor preformed antibodies causing graft loss within a few days. Herein, we have described a case of an ABO-compatible liver transplantation that underwent hyperacute rejection, needing retransplantation for treatment. A 27-year-old man of blood group A positive who displayed fulminant hepatic failure due to hepatitis B (in agreement with the O'Grady criteria), received an ABO-compatible graft. He developed significant asthenia, fever, hypotension, oliguria, and coagulopathy. Ultrasonography revealed total thrombosis of the portal vein and absence of dilatation of bile ducts. The patient was priorized for retransplantation and underwent a good subsequent evolution. On anatomopathologic exam the explant revealed thrombosis of the intrahepatic branches of the portal vein with venous and ischemic infarcts compatible with a diagnosis of hyperacute rejection. The clinical findings of hyperacute rejection were characterized by progressive elevation of bilirubin and thrombocytopenia associated with signs of hepatic failure during the first days after transplantation. In this case, the histological exam was compatible with hyperacute rejection, excluding the diagnoses of hepatic artery thrombosis or biliary obstruction, despite the negative test for anti-HLA antibodies. The diagnosis of hyperacute rejection could be made associated with a short ischemic time and a good response after retransplantation.


Matching into an Orthopedic Residency: Which Application Components Correlate with Final Rank List Order?
To determine if any of the unique elements of the applications of medical students who were granted interviews to an orthopedic residency program correlate to the program's final rank order list of candidate residents. Eight domains of the standard residency application were considered as independent variables for 36 applicants. Personal, identifying information was removed from the application material within each domain, thus blinding the application domains for 5 core faculty members from the program to review and rank independently. These 8 domain rank lists were then compared to the program's final rank list order to determine the correlation of each domain with the final rank list order. Academic medical center. Applicants to a university-based orthopedic surgery residency program who were granted interviews in the 2016 academic year. Two domains of the application correlated with the final rank list order: interview and personal statement. None of the other domains had a significant correlation with the final rank list order. Interobserver variability among the faculty members was high for the rankings of the different domains. Interview and personal statement were the only domains within the application that had correlation with the final rank list for an orthopedic residency program. A better understanding of how these 2 components affect the rank list may provide opportunity for process improvements.


Comparison of effects of lower extremity orthoses on energy expenditure in patients with cerebral palsy.
The aim of the study was to compare the effects of lower extremity orthoses on energy expenditure in patients with cerebral palsy (CP). We included 48 children with CP using lower extremity orthosis. Energy expenditures determined based on heart rate, yielded an energy expenditure index (EEI) with and without orthosis during walking. RESULTS were compared statistically between orthosis groups (solid polyethylene ankle foot orthosis (PAFO), articulated PAFO, ground reaction foot orthosis (GRAFO), plastic and metallic knee-ankle-foot-orthosis (KAFO), and metallic AFO). It was found that an advancement in energy expenditure was seen with plastic orthoses which is more prominent by solid PAFO (p = 0.008). It was concluded that especially solid PAFO can be more beneficial in terms of energy consumption in CP patients. In rehabilitation phase, the EEI measurement was seen to be a useful and practical method for choosing the proper orthosis type.


Relationships between early experience to dietary diversity, acceptance of novel flavors, and open field behavior in sheep.
This study determined whether early experiences by sheep to monotonous or diverse diets influence: (1) plasmatic profiles of cortisol, a hormone involved in stress responses by mammals, before and after an ACTH challenge, (2) the readiness to eat new foods in a new environment, (3) general fearfulness and response to separation--as measured by the open field test (OFT) and stress induced hyperthermia (SIH)--and (4) the link between (2) and (3). Thirty, 2-mo-old lambs were randomly assigned to 3 treatments (10 lambs/treatment). Lambs in one treatment (Diversity--DV) received in successive periods of exposure all possible 4-way choice combinations of 2 foods high in energy and 2 foods high in protein from an array of 6 foods: 3 high in energy (beet pulp, oat grain, and a mix of grape pomace:milo [40:60]) and 3 high in protein (soybean meal, alfalfa, corn gluten meal). Lambs in another treatment (DV+T) received the same exposure described for DV but two phytochemicals, oxalic acid (1.5%) and quebracho tannins (10%) were randomly added within any period of exposure to foods high in energy or to foods high in protein. Lambs in the third treatment (Monotony--MO) received a monotonous balanced ration containing all 6 foods fed to the other groups. After exposure, lambs were offered a choice of the aforementioned 6 foods (DV; DV+T) or the monotonous diet (MO). Lambs were intravenously injected with ACTH 1 h after food presentation, and sampled at 1, 2, and 3 h post feeding for determinations of plasma cortisol concentrations. Reluctance to eat novel flavored foods (onion-, coconut- and cinnamon-flavored wheat bran), open field behavior, and SIH was assessed in all treatments. Lambs in MO showed greater concentrations of plasma cortisol 1 h after food presentation than lambs in the DV or DV+T treatments (P=0.04). However, the difference was small and no differences among treatments were detected after an ACTH challenge (P>0.1). Lambs in DV consumed more onion-flavored wheat bran than lambs in MO (P=0.05). Lambs in DV also showed a greater cumulative consumption of novel flavors on d 2 than lambs in MO (treatment×day; P=0.01). Lambs in DV showed lower increase in rectal temperature (P=0.07) than lambs in MO. Only lambs in DV exhibited a positive relationship between consumption of cinnamon-flavored wheat bran and attempts of escape (R(2)=0.58; P=0.02). Our results suggest that exposure to diverse foods early in life may be less stressful than exposure to monotonous rations, as measured by plasma cortisol concentrations after food ingestion, and by changes in rectal temperature after exposure to the OFT. Lambs exposed to diverse diets early in life may also increase the initial acceptance of new flavors in novel environments relative to lambs exposed early in life to monotonous diets.


Effect of hypoxia on myocardial relaxation in isometric cat papillary muscle.
Myocardial relaxation is an important energy-dependent process. Hypoxia, unlike ischemia, has not been shown to impair myocardial relaxation. This difference may be because (a) the traditional index to assess isometric muscle relaxation (half time to relaxation or RT((1/2))) reflects both changes in developed tension as well as relaxation and (b) the relaxation process is highly sensitive to temperature and previous papillary muscle studies have been conducted under hypothermic conditions. The present study examines the effect of hypoxia on the relaxation process of 31 isometrically contracting kitten papillary muscles at hypothermic (29 degrees C) and euthermic (38 degrees C) conditions using RT((1/2)), the peak rate of tension fall (-dT/dt) and -dT/dt normalized for tension ([peak -dT/dt]/T and max [-dT/dt per T]). Hypoxia at 29 degrees C resulted in a fall in RT((1/2)) from 278+/-11 (SEM) to 230+/-17 ms (P < 0.01) and no change in (peak -dT/dt)/T and max (-dT/dt per T). However, at 38 degrees C, hypoxia impaired relaxation as reflected in a prolongation of RT((1/2)) from 101+/-6 to 126+/-8 ms (P < 0.01) in spite of a substantial fall in peak tension. Moreover, (peak -dT/dt)/T decreased from -15.4+/-0.7 to -11.0+/-0.8/s (P < 0.01) and max (-dT/dt per T) decreased from -25.1+/-1.8 to -13.8+/-0.9/s (P < 0.01). In conclusion, the present study demonstrates that hypoxia impairs the relaxation process of cardiac muscle.


[Tibiocalcaneal arthrodesis with retrograde nails. Description of a hindfoot procedure after massive talus destruction].
Following loss of the talus, tibiocalcaneal fusion is often the only available means of obtaining weight-bearing ability in the lower limb. Length discrepancy may be managed with an allograft. This casuistic describes 6 patients with tibiocalcaneal fusion (mean age 64 years) who had received a structural femoral head allograft fusion for failed total ankle arthroplasty (3 cases), Charcot arthropathy (2 cases) and osteomyelitis (1 case). The mean follow-up was 33 months and all limbs could be salvaged. There were two cases of non-union (one with infection). The mean AOFAS score was 51 and the mean Mazur score was 37. In the SF-36 the mean PCS was 34.4 and the mean MCS was 48.4. It was shown that in the hindfoot, as at other sites, allografts may be used for the filling of major bone defects; however, the patient function will still be massively impaired. Therefore, the procedure should be confined to cases where less complex and less invasive techniques are unlikely to be of benefit.


Population-based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans.
African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. We conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan-Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD. We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65-0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89-1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs. Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD. Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR-γ agonistic properties with beneficial anti-diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.


Enantioselective metabolism of four chiral triazole fungicides in rat liver microsomes.
Triazole fungicides with one or two chiral centers are widely used worldwide. The liver microsomes plays a major role in the metabolism and systemic elimination of chiral pesticides after exposure. In this present work, enantioselective metabolism of four representative chiral triazole fungicides (prothioconazole, flutriafol, triticonazole, and epoxiconazole) in rat liver microsomes (RLM) was investigated using LC-MS/MS. Baseline separation of the four chiral fungicides and prothioconazole-desthio was achieved on Lux-cellulose-1. The results demonstrated that the R-enantiomers of flutriafol and triticonazole were preferentially metabolized with half-life ranged from 17.33 min to 99.00 min. The R,S-epoxiconazole accumulated with a half-life of 173.25 min. There was no stereoselectivity for prothioconazole. However, remarkable stereoselective metabolism was observed for prothioconazole-desthio. The results of enzyme kinetic revealed different affinities between the enantiomers and metabolic enzymes. In addition, homologous modeling and molecular docking results indicated that enantioselectivity were partially to enantiospecific binding affinities with CYP enzymes. This study highlights a new quantitative approach for stereoselective metabolism of chiral agrochemicals and provides more accurate data on risk assessment of triazole fungicides.


Pro-oxidant versus anti-oxidant effects of seeds aglycone extracts of Lepidium sativum and Eruca vesicaria Linn., in vitro, and on neutrophil nitro-oxidative functions.
This study evaluated the anti-inflammatory and antioxidant properties of seeds aglycone extracts from Lepidium sativum (LS) and Eruca vesicaria (EV) Linn., on oxidative damages in vitro and on neutrophil nitro-oxidative functions. The results showed that LS and EV aglycone extracts attenuated liver microsomal lipids and proteins oxidation through a potent antioxidant effect as attested by the dose dependent quenching of DPPH radical scavenging activity. LS and EV aglycone extracts inhibited dose dependently the production of superoxide anion by BALB/c mice-derived peritoneal neutrophils, whereas they slightly enhanced exocytosis of myeloperoxidase (MPO), a marker of azurophilic granules. Interestingly, only LS replenished glutathione (GSH) and nitric oxide levels, indicating a fine differential effect. This study highlighted the subtle oxidative and antioxidant capacity of LS and EV seeds aglycone extracts. These health promoting compounds could be used to finely modulate critical events involved in microbial infection, inflammation and nitro-oxidative stress.


Blood and CSF acid-base changes, and rate of ventilatory acclimatization of awake dogs to 3,550 m.
Awake, intact dogs trained to wear a respiratory mask were studied in a hypobaric chamber at 140 m and at various stages of a 4-week exposure to 3,550 m. Resting ventilation, pulmonary gas exchanges, arterial blood gases and pH, acid-base status of the cisternal fluid (CSF) and ventilatory responses to transient O2 inhalation were measured. Attention is focussed on the time course of ventilatory acclimatization to altitude, characterized by hyperventilation with hypocapnia and a consequent increase of arterial Po2. (1) 75 percent of the increment in pulmonary ventilation due to hypoxia was achieved in 30 minutes; (2) the further increase, 25 percent of the total hyperventilation, was complete after 3 hr, with a corresponding Pco2 drop and pH increase in blood and CSF, and an increase in Pao2; (3) the secondary increase in ventilation, beyond the acute exposure period, was not related to return of [H+] in CSF towards control value; (4) the large transient decrease of ventilation following brief oxygen inhalation demonstrated a strong arterial chemoreflex drive in acclimatized animals. The extremely rapid ventilatory acclimatization to moderately high altitude in normal dogs appears to be mediated not by CSF hydrogen ion concentration but by a strong chemoreflex drive of ventilation.


Fresh gas flow and carbon dioxide rebreathing in a low pressure semi-open anaesthesia system.
We have constructed a simple system for field anaesthesia by using a Farman entrainer and a semi-open circuit to convert a draw-over apparatus to a continuous flow air/O2 system. Compressed O2 was the driving gas for the entrainer; fresh gas (FG) delivered to the semi-open circuit was a mixture of O2, entrained air and anaesthetic vapour. The purpose of this study was to examine FG flow rate and CO2 rebreathing during intermittent positive pressure ventilation (IPPV). A non-rebreathing inflation valve (Laerdal) placed at the end of the expiratory (efferent) limb of the circuit vented both expiratory gas and excess FG. Ambient air IPPV was applied through the Laerdal valve from a self-inflating bag or ventilator. Since this circuit is functionally similar to a T-piece, the gas from the efferent limb (340 ml, containing FG) entered the lungs first. If tidal volume was larger than 340 ml the balance was ambient air. Minute ventilation of the lungs with efferent limb gas was defined as Veff. Respiratory gas was sampled at the endotracheal tube and the CO2 tension was measured with a NIHON-KOHDEN CO2 analyzer. Thirty-seven adult patients having intra-abdominal or pelvic surgery under general tracheal anaesthesia were studied. Four FG flow rates (5.7, 8.0, 9.3, and 10.4 L.min-1), corresponding to driving gas pressures of 40, 60, 80, and 100 mmHg, were introduced in random order. Although inspired CO2 was detected at FG flow rates of 5.7-9.3 L.min-1, there were no differences in PETCO2 among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Percutaneous closure of perimembranous ventricular septal defect associated with a ventricular septal aneurysm using the Amplatzer ductal occluder.
Amplatzer ductal occluders were used for percutaneous closure of perimembranous ventricular septal defects with associated ventricular septal aneurysm in three patients. The device was well positioned and the ventricular left-to-right shunt was significantly decreased in all three patients. The procedure was tolerated well without complications in each case.


Nomogram Analysis of Clinical Characteristics and Mortality Risk Factor of Non-Fermentative Gram-Negative Bacteria-Induced Post-Neurosurgical Meningitis.
To explore the clinical characteristics of post-neurosurgical meningitis (PNM) patients infected with nonfermenting Gram-negative bacilli (NFGNB) and to evaluate the related mortality risk factors. A cohort analysis of PNM patients infected with NFGNB in Beijing Tiantan Hospital and Capital Medical University from 2012.1 to 2020.12. The microbial distribution, antimicrobial sensitivity and genotypes were tested, and potential mortality risk factors were evaluated using Mann-Whitney U or chi-squared tests. Independent risk factors for mortality were established by constructing a logistic model. A total of 2940 PNM patients were enrolled in this study, of whom 207 (17.1%) were infected with NFGNB. Among these patients, 29 died of NFGNB meningitis, with an overall mortality rate of 14.0%. The top three NFGNBs were Acinetobacter baumannii (105 cases, 50.7%), Pseudomonas aeruginosa (29 cases, 14.0%) and Acinetobacter lwoffii (20 cases, 9.7%). Nomogram analysis revealed that hypertension (OR 4.551, 95% CI: 1.464-14.154, P = 0.009), external ventricular drainage (EVD) (OR 3.944, 95% CI: 1.286-12.095, P = 0.016), and assisted mechanical ventilator (AMV) (OR 6.192, 95% CI: 1.737-22.081, P = 0.005) were independent risk factors for mortality. In addition, antibiotic prophylaxis was shown to play a vital role in NFGNB-induced PNM therapy. PNM patients infected with NFGNB have a high mortality rate. Hypertension, EVD and AMV were independent mortality risk factors, and clinical attention should be paid to their prevention and treatment.


Combined high-dose sub-tenon triamcinolone, intravitreal bevacizumab, and laser photocoagulation for refractory diabetic macular edema: a pilot study.
To study the efficacy and safety of triple therapy (sub-Tenon triamcinolone [∼70 mg], intravitreal bevacizumab [1.25 mg], and focal/grid laser) for refractory diabetic macular edema. Twenty-nine eyes of 29 patients who received triple therapy were monitored for central foveal thickness, best-corrected visual acuity (BCVA), and side effects over a 1-year period. Their results were compared with a focal/grid laser historical control group of 18 eyes (18 patients). In the triple therapy group, mean central foveal thickness significantly reduced from baseline value of 441 μm to 298 μm at Month 12 (P < 0.001), but there was no significant change of BCVA. In the control group, there were no sustained significant changes of central foveal thickness or BCVA. A subgroup analysis of 7 eyes in the triple therapy group with baseline BCVA of ≤20/100 showed significant BCVA improvements from 4 weeks to 9 months. The maximum improvement was achieved at 6 months, when the mean BCVA improved by 9.5 Early Treatment Diabetic Retinopathy Study letters from baseline. Intraocular pressure rise (31.0%), partial ptosis (17.2%), and significant cataractogenesis (8.7%) were encountered in the triple therapy group but not in the control group. Sustained reduction of central foveal thickness was achieved with triple therapy over the 1-year study period. Significant visual improvement was seen only in patients with worse baseline BCVA, but not in the triple therapy group as a whole. Significant side effects of intraocular pressure rise, ptosis, and cataractogenesis were encountered in the triple therapy group.


Lost in translation? microRNAs at the rough ER.
MicroRNAs (miRNAs) function to post-transcriptionally regulate target RNAs, including long non-coding RNAs and mRNAs. A recent study demonstrates that Arabidopsis miRNAs are enriched at the rough endoplasmic reticulum (ER). This enrichment is a surprise, given that most known miRNA targets are not expected to be translated at the rough ER.


Polychlorinated naphthalene concentrations and distribution in feed raw materials.
Concentrations and patterns of 75 PCN congeners in feed raw materials of animal and plant origin were investigated. Six types of feed raw materials of animal origin and three types of feed raw materials of plant origin from China were collected in 2016. The total concentrations of PCNs in the collected materials ranged from 147 to 1009 ng kg-1, with the highest occurring in fish meal. The mean PCNs concentration in feed raw materials of animal origin (551 ng kg-1) was higher than in those of plant origin (294 ng kg-1). Additionally, lower chlorinated PCNs were the main homologues in raw feed materials, while Di-CNs were the predominant homologues in all samples (mean: 53%), followed by tri-CNs (mean: 28%). The most abundant congeners were CN5/7 and 24/14. Additionally, the toxicity equivalencies (TEQs) of PCNs in the feed raw materials ranged from 0.010 to 0.046 ng TEQ kg-1, with the highest TEQ concentrations of PCNs detected in gluten meal. Together, CN5/7, 66/67, 65/70, and 73 contributed approximately 64% of the total PCN TEQs in raw feed materials. Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in the feed raw materials were detected to compare the TEQ distribution of those dioxin-like compounds. The mass concentrations of PCNs were 1-3 orders of magnitude higher than those of PCDD, PCDFs and PCBs, while the TEQ concentrations of PCNs contributed 2.0%-6.5% of the total TEQs of PCNs, PCDDs, PCDFs and PCBs in the feed raw materials.


Efficacy of Essential Trace Elements Supplementation on Mineral Composition, Sperm Characteristics, Antioxidant Status, and Genotoxicity in Testis of Tebuconazole-treated Rats.
This research was performed to evaluate the effect of tebuconazole (TBZ) on reproductive organs of male rats and to assess the protective role of combined essential trace elements in alleviating the detrimental effect of TBZ on male reproductive function. For this purpose, 48 rats were exposed to 100 mg/kg TBZ, TBZ supplemented with zinc (Zn), selenium (Se), copper (Cu), and iron (Fe), TBZ + (Se + Zn); TBZ + Cu; or TBZ + Fe. The experiment was conducted for 30 consecutive days. TBZ caused a significant perturbation in mineral levels and reduction in reproductive organs weights, plasma testosterone level, and testicular antioxidant enzyme activities. The TBZ-treated group also showed a significant increase in sperm abnormalities (count, motility, and viability percent), plasma follicle-stimulating hormone and luteinizing hormone concentrations, lipid peroxidation, protein oxidation, and severe DNA degradation in comparison with the controls. Histopathologically, TBZ caused testis impairments. Conversely, treatment with trace elements, in combination or alone, improved the reproductive organ weights, sperm characteristics, TBZ-induced toxicity, and histopathological modifications in testis. TBZ exerts significant harmful effects on male reproductive system. The concurrent administration of trace elements reduces testis dysfunction, fertility, and toxicity induced by TBZ.


Correction: Farshadmand et al. Utility of Cardiac Power Hemodynamic Measurements in the Evaluation and Risk Stratification of Cardiovascular Conditions. Healthcare 2022, 10, 2417.
Zachary Lowy was not included as an author in the original publication [...].


Publisher Correction: Parallel evolution in the emergence of highly pathogenic avian influenza A viruses.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20006-5.


Total body irradiation-an attachment free sweeping beam technique.
A sweeping beam technique for total body irradiation in standard treatment rooms and for standard linear accelerators (linacs) is introduced, which does not require any accessory attached to the linac. Lung shielding is facilitated to reduce the risk of pulmonary toxicity. Additionally, the applicability of a commercial radiotherapy planning system (RTPS) is examined. The patient is positioned on a low couch on the floor, the longitudinal axis of the body in the rotational plane of the linac. Eight arc fields and five additional fixed beams are applied to the patient in supine and prone position respectively. The dose distributions were measured in a solid water phantom and in an Alderson phantom. Diode detectors were calibrated for in-vivo dosimetry. The RTPS Oncentra was employed for calculations of the dose distribution. For the cranial 120 cm the longitudinal dose profile in a slab phantom measured with ionization chamber varies between 94 and 107 % of the prescription dose. These values were confirmed by film measurements and RTPS calculations. The transmittance of the lung shields has been determined as a function of the thickness of the absorber material. Measurements in an Alderson phantom and in-vivo dosimetry of the first patients match the calculated dose. A treatment technique with clinically good dose distributions has been introduced, which can be applied with each standard linac and in standard treatment rooms. Dose calculations were performed with a commercial RTPS and should enable individual dose optimization.


Effects of toluene, styrene, trichloroethylene, and trichloroethane on the vestibulo-and opto-oculo motor system in rats.
The acute effects of inhalation of four solvents on the central vestibular system of rats were analyzed by recording eye movements upon different stimuli. The dose-response relationship was investigated. Optokinetic stimulation was obtained by placing the animals in front of a surrounding visual pattern, moving at different velocities. The slow-phase eye velocity (SPV) of nystagmus was calculated and divided by the stimulus velocity, giving the gain. All the solvents caused a decrease of the gain. Vestibular stimulation was performed on a turntable by an angular acceleration/deceleration in darkness. The SPV and the duration of the post-stimulatory nystagmus were calculated. The shape of the SPV dose-response curves differed among the four solvents. Toluene, styrene, and trichloroethylene prolonged the duration of nystagmus while trichloroethane did not. A conflicting vestibular and optokinetic stimulation was performed by an angular acceleration/deceleration with a surrounding visual pattern moving with the turntable. All solvents decreased the ability to cancel nystagmus, elicited by vestibular stimulation in conflict with a visual input. Quick movements of the eyes, saccades, were elicited by tactile stimulation. Toluene, styrene, and trichloroethylene changed the generation of the saccades while trichloroethane did not. Most of the findings indicate a common site of action in the central vestibular system, viz, the cerebellar-vestibular circuit. However, within this domain, there are evident differences in the effects among the solvents. This findings, together with previous results obtained in other experimental models of the central nervous system (CNS), suggest that different solvents should be considered as individual compounds.(ABSTRACT TRUNCATED AT 250 WORDS)


A case of Rh isoimmunization: should threatened first-trimester abortion be an indication for Rh immune globulin prophylaxis?
Despite the recommended 28 weeks' gestation antenatal, postnatal, and postabortion prophylaxis with Rh immune globulin, residual Rh immunization still occurs in Rh-negative women. We describe a patient whose history suggests development of an anti-D antibody after first-trimester bleeding. To our knowledge, this is the first such case reported in the English literature.


Changes in corneal endothelial cells after trabeculectomy and EX-PRESS shunt: 2-year follow-up.
To compare trabeculectomy and EX-PRESS device implantation procedures for treating glaucoma and evaluate changes in corneal endothelial cell density (CECD). This study prospectively evaluated changes in the CECD in 60 eyes of 60 patients who underwent trabeculectomy and 50 eyes of 45 patients who underwent EX-PRESS device implantation. Baseline patient data recorded included age at surgery, sex, type of glaucoma medications, and lens status. Using a noncontact specular microscope, corneal specular microscopy was performed preoperatively at the central cornea and then at 6, 12, 18 and 24 months after surgery. CECD before and after surgery was compared using a paired t-test. There was a significant decrease in the IOP and number of antiglaucoma medications in both groups after the surgery. The mean CECD in the trabeculectomy group was 2505 ± 280 cells/mm2 at baseline, while it was 2398 ± 274 cells/mm2 (P < 0.001), 2349 ± 323 cells/mm2 (P < 0.001), 2293 ± 325 cells/mm2 (P < 0.001), and 2277 ± 385 cells/mm2 (P = 0.003) at 6, 12, 18, and 24 months, respectively. However, the CECD in the EX-PRESS group was 2377 ± 389 cells/mm2 at baseline, while it was 2267 ± 409 cells/mm2 (P = 0.007), 2292 ± 452 cells/mm2 (P = 0.043), 2379 ± 375 cells/mm2 (P = 0.318), and 2317 ± 449 cells/mm2 (P = 0.274) at 6, 12, 18, and 24 months, respectively. As compared to trabeculectomy, EX-PRESS device implantation appears to be a safer procedure with regard to the endothelial cell loss risk.


Transcortical Endoscopic Removal of Residual Craniopharyngioma in the Third Ventricle: Surgical Video.
Excision through craniotomy is used for pediatric craniopharyngioma removal. However, residual tumors can sometimes be found in the blind spot of the microscopic field, such as the third ventricle wall, back of the optic chiasm, and brainstem surface, during surgery. Video 1 demonstrates the surgery using a flexible endoscope for the removal of residual tumor located within the blind spot of the first resection. The written consent was obtained from the patient's family. A 4-year-old child complained of vomiting, and the radiologic findings showed obstructive hydrocephalus and a calcified suprasellar mass lesion that extended to the third ventricle. The tumor was treated with a right frontotemporal craniotomy. The pathologic diagnosis was craniopharyngioma. Postoperative magnetic resonance imaging showed residual tumor detected at the roof of the third ventricle, back of the optic chiasm, and interpeduncular fossa. The residual tumors were removed using a flexible endoscope via a transcortical, transventricular approach. Postoperative magnetic resonance imaging showed no residual tumors. Although histologically benign, craniopharyngiomas may be locally aggressive and their close proximity to vital structures makes them one of our controversial management dilemmas. Recurrence may occur following even a presumed total excision and radiation therapy. Residual tumors located in the third ventricle are resected through various approaches, such as the transsphenoidal or transcallosal approach. Our approach using a flexible endoscope was minimally invasive and useful for the removal of residual tumor of the third ventricle in craniopharyngioma surgery because the approach offered a wide field of view and visual angle and forceps could be applied according to the view.


Knockout of Atg5 delays the maturation and reduces the survival of adult-generated neurons in the hippocampus.
Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays important roles in cell maintenance, expansion and differentiation. Removal of genes essential for autophagy from embryonic neural stem and precursor cells reduces the survival and inhibits neuronal differentiation of adult-generated neurons. No study has modified autophagy within the adult precursor cells, leaving the cell-autonomous role of autophagy in adult neurogenesis unknown. Here we demonstrate that autophagic flux exists in the adult dividing progenitor cells and their progeny in the dentate gyrus. To investigate the role of autophagy in adult hippocampal neurogenesis, we genetically deleted Autophagy-related gene 5 (Atg5) that reduced autophagic flux and the survival of the progeny of dividing progenitor cells. This significant reduction in survival of adult-generated neurons is accompanied by a delay in neuronal maturation, including a transient reduction in spine density in the absence of a change in differentiation. The delay in cell maturation and loss of progeny of the Atg5-null cells was not present in mice that lacked the essential pro-apoptotic protein Bax (Bcl-2-associated X protein), suggesting that Atg5-deficient cells die through a Bax-dependent mechanism. In addition, there was a loss of Atg5-null cells following exposure to running, suggesting that Atg5 is required for running-induced increases in neurogenesis. These findings highlight the cell-autonomous requirement of Atg5 in the survival of adult-generated neurons.


Mechanism of cassava tuber cell wall weakening by dilute sodium hydroxide steeping.
Steeping of cassava root pieces in 0.75% NaOH in combination with wet milling was investigated to determine whether and how dilute NaOH modifies cassava cell walls. Gas chromatography data of cell wall constituent sugar composition and Fourier transform infrared (FTIR) data showed that NaOH steeping reduced the level of pectin in cassava cell walls. FTIR and wide-angle X-ray scattering spectroscopy also indicated that NaOH steeping combined with fine milling slightly reduced cellulose crystallinity. Scanning electron microscopy showed that NaOH steeping produced micropores in the cell walls and light microscopy revealed that NaOH steeping increased disaggregation of parenchyma cells. Steeping of ground cassava in NaOH resulted in a 12% decrease in large residue particles and approx. 4% greater starch yield with wet milling. Therefore dilute NaOH steeping can improve the effectiveness of wet milling in disintegrating cell walls through solubilisation of pectin, thereby reduced cell wall strength.


A systematic review of the relationship of diabetes mellitus, depression, and missed appointments in a low-income uninsured population.
The purpose of this systematic literature review was to determine the relationship between the diagnosis of diabetes and depression and missed appointments in a low-income, uninsured, racially heterogeneous, adult population. Research demonstrates that individuals with diabetes have an increased incidence of depression across socioeconomic and racial groups. Low-income individuals have an increased prevalence of depression. The cost and burden of diabetes are greatly increased among individuals with both diabetes and depression versus diabetes alone. The prevalence and effects of diabetes and depression in a low-income, uninsured, racially heterogeneous population have not been determined. Further research to explore the relationship of diabetes, depression, and missed appointments in this vulnerable population is needed before effective treatment models can be developed. Longitudinal studies are also needed to determine the cause and effect between diabetes and depression among all populations.


[Expression of Ietalurus punetaus β-defensin based on recombinant Pichia pastoris].
β-defensin is a primary protein immune factor in channel catfish's (Ietalurus punetaus) resistance to pathogenic microorganisms. Its primary structure contains a signal peptide composed of 24 amino acid residues at the N-terminal and a mature peptide composed of 43 amino acid residues at the C-terminal. The mature peptide region is responsible for the biological activity of β-defensin. In the present study, a recombinant strain of Pichia pastoris that produces channel catfish β-defensin, was constructed to realize the biosynthesis of channel catfish β-defensin based on eukaryotic expression. First, the β-defensin gene "IPBD" was isolated from the skin of channel catfish by RT-PCR. After linking it with the expression vector pPICZA, pPICZA-IPBD was transferred into competent P. pastoris X-33 cells to obtain recombinant P. pastoris strains. The yeast transformants with multi-copy gene inserts were obtained by using the culture medium containing 1 000 μg/mL zeocin. Using BMM culture medium (without amino nitrogen culture medium) instead of BMMY culture medium (with amino nitrogen culture medium), the fermentation and culture conditions of the recombinant strain were optimized, and the optimal conditions for producing channel catfish β-defensin were determined as follows: the expression was induced for 96 h with 1.0% methanol at 28 °C , 250 r/min. Purified protein with molecular weight of 5.98 kDa was obtained by nickel affinity chromatography, and MALDI-TOF/TOF mass spectrometry proved that it was the expected recombinant IPBD. The antibacterial test results showed that the inhibitory rates of recombinant IPBD on Gram-positive Staphylococcus aureus and Listeria monocytogenes and Gram-negative Pseudomonas aeruginosa were 69.6%, 71.6% and 65.8%, respectively. This study provides a recombinant DNA technique for the development of small molecule natural antibacterial peptide from fish.


De novo synthesis and axoplasmic transport of [35S]methionine-substance P in explants of nodose ganglion/vagus nerve.
The synthesis and transport of substance P, the widely distributed undecapeptide, was studied in the vagus nerve of the guinea pig. In preliminary in vivo studies, the cervical vagus nerve was ligated 2 cm distal to the nodose ganglion. Twenty-four hours later, the content of immunoreactive substance P (IR-SP) in the 3-mm nerve segment proximal to ligature was 2147 +/- 207 pg (mean +/- S.E.M.) vs 133 +/- 31 pg in an equal segment of unligated nerve or 243 +/- 55 pg in the nodose ganglion. When the vagus nerve was crushed above the ganglion and simultaneously ligated 2 cm distally, the IR-SP content proximal to the ligature was reduced 50% to 1131 +/- 99 pg (P less than 0.01), while nodose ganglion content increased to 420 +/- 140 pg (n.s.). To confirm that residual transport following supranodose crush was derived from nodose ganglion-synthesized SP, SP synthesis and transport were studied in explants of nodose ganglion and attached distal vagus nerve removed from perfused animals and maintained in vitro for up to 24 h. At the time of resection, nerves were ligated 1.5 cm distal to the ganglion. Twenty-four hours following explantation, IR-SP content in proximal segments was 1022 +/- 142 pg vs 155 +/- 22 pg in unligated segments and 560 +/- 72 pg in the nodose ganglion. Accumulation in the proximal segment was time dependent. In separate experiments, [35S]methionine was added to explant medium and the explants maintained for varying time intervals. Nerve tissue was extracted and subjected to either serial reverse phase high performance liquid chromatography (HPLC), or immunoprecipitation with SP antiserum followed by a single HPLC separation. By 4 h, radiolabeled SP was present in nodose ganglia and lesser amounts in the proximal segments. By 12 h, [35S]SP was present equally in ganglia and proximal segments whereas by 18 h, two-thirds or more of the newly synthesized peptide was present in proximal segments. At 18 h, the quantity of radiolabeled SP covaried with IR-SP content in the individual nerve segments. The addition of cycloheximide to explant medium reduced [35S]SP synthesis by 90%. These studies demonstrate that: (1) approximately 50% of immunoreactive SP transported efferently within the vagus nerve of the guinea pig is derived from the nodose ganglion, (2) de novo SP synthesis within and export from the nodose ganglion occurs within 4 h, (3) the changes in IR-SP content demonstrated in in vivo and in vitro ligation studies accurately reflect ongoing SP synthesis within the nodose ganglion.(ABSTRACT TRUNCATED AT 400 WORDS)


Resolution of the competitive inhibitory effects of lithium and AMPPNP on the beat frequency of ATP-reactivated, demembranated, sea urchin sperm flagella.
About half of the inhibitory effect on the beat frequency of sea urchin spermatozoa flagella by beta, gamma-imido-adenosine-5'-triphosphate (AMPPNP) previously reported by Okuno & Brokaw (1981) was actually the result of inhibition by lithium resulting from the use of a tetralithium salt of AMPPNP. Li+ (or LiATP3-) acts as a competitive inhibitor of beat frequency, with a Ki for Li+ of about 30 mM. Under improved reactivation conditions which reduce the Km for beat frequency to about 0.1 mM, the Ki for lithium-free MgAMPPNP2- is about 2.3 mM, and magnesium pyrophosphate (MgPPi-), which may be an equivalent ligand, gives a Ki of 3.4 mM.


Economic antecedents of sudden infant death syndrome.
To test the hypothesis that labor market contraction is associated with an elevated number of deaths due to sudden infant death syndrome (SIDS). We apply time-series methods to monthly counts of SIDS deaths and total employment from the state of California beginning January 1989 and ending December 2001. The methods control for trends, seasonal cycles, and other forms of autocorrelation that could induce spurious associations. Decreases in the number of employed persons in California preceded higher than expected monthly values of SIDS cases among black, non-Hispanic White and Hispanic infants. In addition, Blacks and Hispanics appear to respond more strongly than non-Hispanic Whites to economic contraction. We infer support for the hypothesis that economic contraction may inhibit salutary behavior related to SIDS. We discuss various mechanisms through which the economy may affect SIDS and recommend further investigation.


"Crown of thorns" single pass lead--clinical results.
Twenty-four patients have been treated for periods of up to two years (mean 14 months) with this single pass electrode for physiological pacing. Manufacturing refinements now allow percutaneous insertion into the subclavian vein. Pacing thresholds and sensing signals from both atrium and ventricle have remained satisfactory for a wide variety of different physiological pacemakers. No complications specifically related to the lead have occurred in a total of 277 patient months. We conclude that this single pass electrode is suitable for long-term implantation and can provide physiological pacing with present day stimulators.


Parental absence during childhood and weight status in adulthood among middle-aged community dwellers in rural Vietnam.
While adverse childhood experiences (ACEs) have been shown to be associated with adulthood obesity, less is known about their association with underweight. We examined the associations between parental absence (i.e., a major component of ACEs) and both underweight and excess weight among middle-aged rural community dwellers in Vietnam, where experiences of parental absence was not uncommon during and after the Vietnam War (1955-1975). Data came from 3000 middle-aged adults who participated in the baseline survey of Khánh Hòa Cardiovascular Study. Parental absence was defined as parental absence due to death, divorce, or out-migration. Using information on the timing of such events, we categorized participants into those who experienced parental absence before the age of 3, between the ages of 3 and 15, and those without such experiences. BMI was calculated based on measured height and weight (kg/m2 ) and categorized into three groups: underweight <18.5; normal 18.5-24.9; excess weight ≥ 25. Multinomial logistic regression was then used to investigate the association between parental absence and adult weight status. Parental absence that occurred before the age of 3 was marginally significantly associated with underweight (relative risk ratio [RRR] = 1.44, 95% confidence interval [CI] 0.95, 2.20) but not with overweight/obesity. Parental divorce was associated with overweight/obesity (RRR = 2.48, 95% CI 1.28, 4.81), but not parental absence due to migratory work. While previous studies in Western settings focused almost exclusively on the risk of obesity in relation to exposure to ACEs, our findings point to the potential importance of considering the risk of underweight in low- and middle-income countries.


Effects of increased temperature on metabolic activity and oxidative stress in the first life stages of marble trout (Salmo marmoratus).
Climate change may result in future alterations in thermal regime which could markedly affect the early developmental stages of cold water fish due to their expected high sensitivity to increasing temperature. In the present study, the effect of temperature increase of 2, 4 and 6°C on the oxygen consumption rate (R), the activity of respiratory electron transport system (ETS) and oxidative stress have been studied in four developmental stages of the marble trout (Salmo marmoratus)-eyed eggs, yolk-sac larvae and juveniles of 1 and 3 months. Oxygen consumption rate and ETS activity increased with level of development and with temperature in all four stages. ETS/R ratios decreased during development and correlated with temperature in eyed eggs, larvae and juveniles of 1 month, but not in juveniles of 3 months. Low ETS/R ratios at higher temperatures indicate stress response in eyed eggs, the most temperature sensitive developmental stage. Catalase (CAT) and glutathione reductase (GR) activities increased during development, but responded differently to elevated temperature in the different developmental stages. Stress in eyed eggs, caused by higher temperatures, resulted in increased oxygen consumption rate and increased activities of CAT and GR. Larvae were sensitive to increased temperature only at the highest experimental temperature of 16°C. Increased temperature did not stress the metabolism of the juveniles, since they were able to compensate their metabolic activity. The earlier developmental stages of marble trout are thus more sensitive to temperature increase than juveniles and therefore more endangered by higher water temperatures. This is the first report connecting oxygen consumption, ETS activity and ETS/R ratio with the activities of antioxidant enzymes in relation to increased temperature in salmonids.


The development of adaptive risk taking and the role of executive functions in a large sample of school-age boys and girls.
The Balloon Analogue Risk Task for Children (BART-C) demands self-regulation of emotion that requires risk-tolerance and adaptive risk-taking to make good decisions under stress (hot cognition). BART-C measures of adaptive risk-taking in 5,409 children K-8th grade were analyzed for improvements by grade, for relationships to executive functioning (EF) and for associations with school characteristics and academic achievement. BART-C improved across grades. Boys showed significantly greater Recklessness, particularly in middle school. EF was a partial mediator between grade and Variability and Recklessness. Better BART-C Total score and less Recklessness were related to lower free-or-reduced-school-lunch percentage and better math and reading proficiency of children's schools. BART-C is a potential "hot-cognition" measure of self-regulation and adaptive risk-taking for children.


A screening method for cervical myelopathy using machine learning to analyze a drawing behavior.
Early detection of cervical myelopathy (CM) is important for a favorable outcome, as its prognosis is poor when left untreated. We developed a screening method for CM using machine learning-based analysis of the drawing behavior of 38 patients with CM and 66 healthy volunteers. Using a stylus pen, the participants traced three different shapes displayed on a tablet device. During the tasks, writing behaviors, such as the coordinates, velocity, and pressure of the stylus tip, along with the drawing time, were recorded. From these data, features related to the drawing pressure, and time to trace each shape and combination of shapes were used as training data for the support vector machine, a machine learning algorithm. To evaluate the accuracy, a receiver operating characteristic curve was generated, and the area under the curve (AUC) was calculated. Models with triangular waveforms tended to be the most accurate. The best triangular wave model identified patients with and without CM with 76% sensitivity and 76% specificity, yielding an AUC of 0.80. Our model was able to classify CM with high accuracy and could be applied to the development of disease screening systems useful outside the hospital setting.


Metrnl deficiency retards skin wound healing in mice by inhibiting AKT/eNOS signaling and angiogenesis.
Meteorin-like (Metrnl) is a novel secreted protein with various biological activities. In this study, we investigated whether and how Metrnl regulated skin wound healing in mice. Global Metrnl gene knockout mice (Metrnl-/-) and endothelial cell-specific Metrnl gene knockout mice (EC-Metrnl-/-) were generated. Eight-mm-diameter full-thickness excisional wound was made on the dorsum of each mouse. The skin wounds were photographed and analyzed. In C57BL/6 mice, we observed that Metrnl expression levels were markedly increased in skin wound tissues. We found that both global and endothelial cell-specific Metrnl gene knockout significantly retarded mouse skin wound healing, and endothelial Metrnl was the key factor affecting wound healing and angiogenesis. The proliferation, migration and tube formation ability of primary human umbilical vein endothelial cells (HUVECs) were inhibited by Metrnl knockdown, but significantly promoted by addition of recombinant Metrnl (10 ng/mL). Metrnl knockdown abolished the proliferation of endothelial cells stimulated by recombinant VEGFA (10 ng/mL) but not by recombinant bFGF (10 ng/mL). We further revealed that Metrnl deficiency impaired VEGFA downstream AKT/eNOS activation in vitro and in vivo. The damaged angiogenetic activity in Metrnl knockdown HUVECs was partly rescued by addition of AKT activator SC79 (10 μM). In conclusion, Metrnl deficiency retards skin wound healing in mice, which is related to impaired endothelial Metrnl-mediated angiogenesis. Metrnl deficiency impairs angiogenesis by inhibiting AKT/eNOS signaling pathway.


High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009-2011.
We conducted a retrospective study on the prevalence and correlates of transmitted drug resistance among newly-diagnosed antiretroviral naive human immunodeficiency virus (HIV) patients in Northern Greece, during the period 2009-11. Transmitted drug resistance was documented in 21.8% of patients enrolled, affecting approximately 40% of subtype A HIV-1-infected individuals. Overcoming challenges due to the ongoing financial crisis, effective preventive measures should be implemented to control further dissemination of resistant HIV strains.


Inhibition of tumour cell invasion by protease inhibitors: correlation with the protease profile.
The invasive potential of eight established human tumour cell lines of different origin has been studied in the Matrigel assay. Between 25% and 70% of the cells migrated through the Matrigel layer within 24 h, indicating that invasiveness varies with the cell type. Semiquantitative measurements of the proteases MMP-2 and MMP-9, and cathepsins B and L were performed in these cell lines and the cell culture media. High invasive potential was found in those cell lines expressing high levels of cathepsins B and L or matrix metal proteases (MMP), either alone or in combination. Overexpression of one of these enzymes is enough to explain a high invasive potential of a cell line. Selective protease inhibitors at 10 nM concentration in the culture medium were used to inhibit the migration of tumour cells in the Matrigel assay. The MMP inhibitor Batimastat reduced the invasive potential of all cell lines studied independently of the MMP expression. The effect of cysteine protease inhibitors was strongly correlated with the protease profile of the tumour cell line. Our findings support the hypothesis of a very complex activation cascade of matrix-degrading proteolytic enzymes and they underline the need to analyse the protease profile of any tumour before beginning an antiproteolytic tumour treatment.


Corrigendum: Physiological and Biochemical Effects of Intrinsically High and Low Exercise Capacities Through Multiomics Approaches.
[This corrects the article DOI: 10.3389/fphys.2019.01201.].


The association of infantile osteopetrosis and neuronal storage disease in two brothers.
Neurological manifestations in infantile osteopetrosis are common and varied, and not always attributable to the skeletal pathology. An unusual association of osteopetrosis with neuronal storage of ceroid lipofuscin is reported in two infant brothers born of nonconsanguinous parents. The first child became symptomatic at age 5 days with weight loss and vomiting. He had poor head control, hypertonia, and persistent fisting, and died at age 2 months. In the second infant, the diagnosis of osteopetrosis was confirmed at age 2 days. His neurological symptoms included blindness, deafness, and recurrent seizures. The infant died at 7 months of age. In both cases, autopsy confirmed the diffuse bony sclerosis with hepatosplenomegaly and extramedullary hematopoiesis. Neuropathological examination revealed cerebral atrophy with ventricular dilation, neuronal loss, and astrogliosis. The most striking finding was widespread accumulation of neuronal ceroid lipofuscin associated with formation of axonal spheroids. The optic nerves were compressed at the optic foramina and showed loss of myelinated axons and gliosis. Rapid Golgi impregnations of neurons from the calcarine cortex in the second infant were analyzed quantitatively, showing a reduction in the total dendritic length and number of branches. The primary defect in osteopetrosis is thought to be a lysosomal dysfunction involving the monocyte cell line from which osteoclasts are derived. Thus, the association in two brothers of osteopetrosis with accumulation of neuronal ceroid lipofuscin may not be fortuitous. The neuronal storage disorder in this instance probably reflects lysosomal dysfunction.


Effects of static high compression on human foot-ankle: biomechanical response and injuries.
To reduce road-traffic fatalities, significant improvements have been seen in the protection of vital body parts. Attention is now focused on serious injuries, which cause disability or impairment as lower limb injuries. The numerical models developed to have a better understanding of injury parameters are evaluated from human responses to load. For this objective, mechanical characterisation tests have been performed on nine human foot/ankle specimens. The responses of three foot contact points during various static loads of the tibia were studied. After each test, an autopsy was performed and the associated injuries were noticed. These tests allowed quantification of the tibia compressive force in relation to foot and ankle deformations up to injury level.


The dynamics of dopamine metabolism in various regions of rat brain.
Dopamine metabolism was studied in various regions of rat brain by following the decline of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) from brain after treatment with pargyline, or from the accumulation of the acids after treatment with probenecid. The decline of DOPAC and HVA after pargyline treatment appeared exponential in all regions of brain studied with half-lives of about 13 min for HVA and 6.5 min for DOPAC. DOPAC was the major metabolite of dopamine, with various brain regions producing between 2-5 times more DOPAC than HVA. HVA accumulated after treatment with probenecid but the accumulation in 1 h did ot account for all of the HVA apparently eliminated from brain. DOPAC accumulated in some regions of brain (medulla, hypothalamus and midbrain) and not in others (cerebellum, cortex, striatum and hippocampus) after probenecid treatment. We conclude that dopamine metabolism is not uniform in brain and that the accumulation of DOPAC and HVA in brain after probenecid treatment only accounts for a minor fraction of the dopamine formed in brain.


Autophagy promotes jasmonate-mediated defense against nematodes.
Autophagy, as an intracellular degradation system, plays a critical role in plant immunity. However, the involvement of autophagy in the plant immune system and its function in plant nematode resistance are largely unknown. Here, we show that root-knot nematode (RKN; Meloidogyne incognita) infection induces autophagy in tomato (Solanum lycopersicum) and different atg mutants exhibit high sensitivity to RKNs. The jasmonate (JA) signaling negative regulators JASMONATE-ASSOCIATED MYC2-LIKE 1 (JAM1), JAM2 and JAM3 interact with ATG8s via an ATG8-interacting motif (AIM), and JAM1 is degraded by autophagy during RKN infection. JAM1 impairs the formation of a transcriptional activation complex between ETHYLENE RESPONSE FACTOR 1 (ERF1) and MEDIATOR 25 (MED25) and interferes with transcriptional regulation of JA-mediated defense-related genes by ERF1. Furthermore, ERF1 acts in a positive feedback loop and regulates autophagy activity by transcriptionally activating ATG expression in response to RKN infection. Therefore, autophagy promotes JA-mediated defense against RKNs via forming a positive feedback circuit in the degradation of JAMs and transcriptional activation by ERF1.


Exosomes as a modulator of immune resistance in human cancers.
In the tumor microenvironment (TME), exosomes secreted by cells form interactive networks between the tumor cells and immune cells, thereby regulating immune signaling cascades in the TME. As key messengers of cell-to-cell communication in the TME, exosomes not only take charge of tumor cell antigen presentation to the immune cells, but also regulate the activities of immune cells, inhibit immune function, and, especially, promote immune resistance, all of which affects the therapeutic outcomes of tumors. Exosomes, which are small-sized vesicles, possess some remarkable advantages, including strong biological activity, a lack of immunogenicity and toxicity, and a strong targeting ability. Based on these characteristics, research on exosomes as biomarkers or carriers of tumor therapeutic drugs has become a research hotspot in related fields. This review describes the role of exosomes in cell communications in the TME, summarizes the effectiveness of exosome-based immunotherapy in overcoming immune resistance in cancer treatment, and systematically summarizes and discusses the characteristics of exosomes from different cell sources. Furthermore, the prospects and challenges of exosome-related therapies are discussed.


Increase of optical illusion in demented patients.
Assuming a particular psychological function of optical gestalt perception, its impairment would lead to a decreasing extent of gestalt related optical illusion. An increase of optical illusion would be expected in the case of a loss of adaptability and cognitive compensation, usually revising the phenomenon of optical illusion. 16 demented out-patients were compared to 16 hospitalized schizophrenics by a 'Computerized Assessment of Change in Optical Illusion' (CACOI), measuring the extent of optical illusion by patient's assessment of 12 variations of the figure of Mueller-Lyer, differing in baseline length. The results showed a significant increase of optical illusion in demented patients compared to the schizophrenic controls (p = 0.019). Taking into account that the extent of optical illusion by the figure of Mueller-Lyer usually is decreasing with age and was found to be increased in schizophrenics, our results support the hypothesis of an early loss of adaptability and cognitive compensation in dementia.