Engineered Bacterial Outer Membrane Vesicles as Controllable Two-Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy.
The most immune cells infiltrating tumor microenvironment (TME), tumor-associated macrophages (TAMs) closely resemble immunosuppressive M2-polarized macrophages. Moreover, tumor cells exhibit high expression of CD47 "don't eat me" signal, which obstructs macrophage phagocytosis. The precise and efficient activation of TAMs is a promising approach to tumor immunotherapy; however, re-education of macrophages remains a challenge. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic nanovesicles that can robustly stimulate macrophages. Here, an OMV-based controllable two-way adaptor is reported, in which a CD47 nanobody (CD47nb) is fused onto OMV surface (OMV-CD47nb), with the outer surface coated with a polyethylene glycol (PEG) layer containing diselenide bonds (PEG/Se) to form PEG/Se@OMV-CD47nb. The PEG/Se layer modification not only mitigates the immunogenicity of OMV-CD47nb, thereby remarkedly increasing the dose that can be administered safely through intravenous injection, but also equips the formulation with radiation-triggered controlled release of OMV-CD47nb. Application of radiation to tumors in mice injected with the nanoformulation results in remodeling of TME. As two-way adaptors, OMV-CD47nb activates TAM phagocytosis of tumor cells via multiple pathways, including induction of M1 polarization and blockade of "don't eat me" signal. Moreover, this activation of TAMs results in the stimulation of T cell-mediated antitumor immunity through effective antigen presentation.


[Dynamic observation of pathological changes and expression of nuclear factor-kappaB in the intestinal mucosa of rats after diffuse brain injury].
To investigate the dynamic pathological changes in the intestinal mucosa of rats and the role of activation of nuclear factor-kappaB (NF-kappaB) in the alteration in intestinal mucosal barrier dysfunction after diffuse brain injury. The animal model established by Marmarou was used to produce diffuse brain injury. One hundred and fifty male Wistar rats were randomly divided into nine groups in terms of postinjury time: 1, 2, 4, 8, 12, 24, 48, 72, 168 hours after injury, and control group. Mucosal thickness, villous height and width were estimated under light microscope, and expression of NF-kappaB was assessed with immunohistochemical staining in control group to compare with those in injury groups. Mucosal thickness, villous height and width were diminished and the optical density of expression of NF-kappaB was much higher in the injury groups than those of control group. The structure of intestinal mucosa is damaged in the earlier stages after diffuse brain injury. NF-kappaB is activated by cellular stress, which may be involved in the pathogenesis of secondary intestinal lesion.


Changing summer precipitation variability in the Alpine region: on the role of scale dependent atmospheric drivers.
Summer precipitation totals in the Alpine Region do not exhibit a systematic trend over the last 120 years. However, we find significant low frequency periodicity of interannual variability which occurs in synchronization with a dominant two-phase state of the atmospheric circulation over the Alps. Enhanced meridional flow increases precipitation variability through positive soil moisture precipitation feedbacks on the regional scale, whereas enhanced zonal flow results in less variability through constant moisture flow from the Atlantic and suppressed feedbacks with the land surface. The dominant state of the atmospheric circulation over the Alps in these periods appears to be steered by zonal sea surface temperature gradients in the mid-latitude North Atlantic. The strength and the location of the westerlies in the mid-latitude Atlantic play an important role in the physical mechanisms linking atmosphere and oceanic temperature gradients and the meridional/zonal circulation characteristics.


A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244).
We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤ 51% was acceptable. Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.


Is methamphetamine abuse a risk factor in parkinsonism?
Parkinsons disease (PD) is a neurodegenerative disorder with increased incidence in individuals beyond 50 years of age. The etiology of PD is currently not known, but it appears that environmental factors may play an important role. The molecular basis of PD is the nearly complete loss of the neurotransmitter dopamine (DA) in the basal ganglia (caudate/putamen). The decrease in dopamine levels is the result of degeneration of dopamine-containing neurons in the substantia nigra. This biochemical deficit in the nigrostriatal pathway leads to the emergence of motor impairments typical of PD. Methamphetamine (METH) is a psychostimulant drug with increasing use in certain segments of the population in the United States and worldwide. In experimental animal models and human studies, METH administration has been shown to decrease markers of dopaminergic neuron terminal integrity in the basal ganglia. A long-standing question has been whether the reductions in dopaminergic markers induced by METH constitute degenerative changes or reflect drug-induced modulation. Resolving this question is important because the irreversible loss of dopaminergic function may increase the likelihood of Parkinsonism with advancing age.


Supersensitivity of coronary arteries in variant angina to spasm induced by intracoronary acetylcholine.
Acetylcholine (20 to 100 micrograms) was infused directly into coronary arteries in 10 patients with variant angina (group A), 13 subjects without coronary artery disease (group B) and 8 patients with significant organic coronary artery stenosis (greater than or equal to 50%) but without variant angina (group C) during coronary arteriography, to clarify the action of this agent on coronary arteries. Temporary pacing was performed at a demand heart rate of 40 beats/min while bradyarrhythmia developed. Coronary arteriography after administration of acetylcholine showed coronary vasoconstriction in all 10 patients (100%) of group A. Angina accompanied by electrocardiographic ischemic changes in 9 of 10 (90%, 7 ST-segment elevation and 2 depression) was provoked during this test. In the patients of group B, acetylcholine also induced vasoconstriction in 8 of 22 (36%) coronary arterial systems examined, chest pain in 3 (14%) and ST-segment deviation in none (0%). In the patients of group C, acetylcholine induced vasoconstriction in 3 of 9 (33%), chest pain in 2 (22%) and ST-segment depression in 1 (11%). No definite coronary artery dilation induced by acetylcholine was noted. Coronary vasoconstriction (p less than 0.05), electrocardiographic ischemic findings (p less than 0.01) and chest pain (p less than 0.01) were induced significantly more frequently in group A than in both groups B and group C. No significant difference was found between group B and group C. The coronary arteries in the patients with variant angina seem to be more susceptible to acetylcholine than those of patients without variant angina irrespective of the presence of significant atherosclerosis.


Comparison of the phagocytosis of two types of cyclosporin (SDZ OXL 400 and SDZ IMM 125) by alveolar macrophages from hamsters.
The aim of this study was to compare two types of cyclosporin (Cs) particles, SDZ OXL 400 and SDZ IMM 125, the latter being more hydrophilic, to understand their uptake by airway macrophages. Alveolar macrophages (AM), harvested by bronchoalveolar lavage (BAL) of hamster lungs, were cultured with two different doses (0.1 mg and 0.5 mg) for 1 h, 6 h, and 24 h. Control incubations without Cs particles or with latex particles were carried out simultaneously. Cell viability, cell activation (i.e., respiratory burst, interleukin-6 (IL-6) synthesis) and mean volume of particles phagocytosed per macrophage were measured. Both types of Cs particles did not modify the AM viability, and failed to induce IL-6 synthesis during phagocytosis but slightly decreased the cell oxidative respiratory burst. The comparison between SDZ OXL 400 and SDZ IMM 125 showed that for the lower dose the mean volume of both Cs types phagocytosed was similar at 1 h and 6 h. At 24 h an increase of the mean volume phagocytosed was seen for SDZ IMM 125 but not for SDZ OXL 400. For the higher dose the mean volume of SDZ IMM 125 phagocytosed was higher than SDZ OXL 400 at 1 h and 6 h and comparable for both types at 24 h. SDZ IMM 125 particles were phagocytosed more rapidly than SDZ OXL 400. The mean volume of phagocytosed latex particles increased with time and dose and was higher than for both Cs particle types. In conclusion, AM were seen to phagocytose particles of different physical properties (i.e., form, size, and shape), chemical properties (i.e., inert or peptidic) and degrees of hydrophilicity in a different manner.


[Securing the use of thermosensitive drugs].
The safety of patient care entails complying with the temperature requirements for thermosensitive drugs. Field studies carried out at the CHU de Caen University Hospital have demonstrated that patients and caregivers do not understand the critical aspect of thermosensitive drugs. This observation has led to the development of tools designed to secure the cold chain for thermosensitive drugs and to increase awareness among healthcare professionals.


Draft Genome Sequence of Bradyrhizobium denitrificans K2, Cultivated from an Air Ventilation Environment.
Bradyrhizobium denitrificans K2, isolated from an air circulation environment, has potential genes participating in inorganic nitrogen and carbon cycling. The draft genome comprises 8.31 Mb, with 7,982 coding sequences and 64.81% average G+C content. Genes related to carbon and inorganic nitrogen cycling were observed in the draft genome.


Deep Convolutional Encoder-Decoder algorithm for MRI brain reconstruction.
Compressed Sensing Magnetic Resonance Imaging (CS-MRI) could be considered a challenged task since it could be designed as an efficient technique for fast MRI acquisition which could be highly beneficial for several clinical routines. In fact, it could grant better scan quality by reducing motion artifacts amount as well as the contrast washout effect. It offers also the possibility to reduce the exploration cost and the patient's anxiety. Recently, Deep Learning Neuronal Network (DL) has been suggested in order to reconstruct MRI scans with conserving the structural details and improving parallel imaging-based fast MRI. In this paper, we propose Deep Convolutional Encoder-Decoder architecture for CS-MRI reconstruction. Such architecture bridges the gap between the non-learning techniques, using data from only one image, and approaches using large training data. The proposed approach is based on autoencoder architecture divided into two parts: an encoder and a decoder. The encoder as well as the decoder has essentially three convolutional blocks. The proposed architecture has been evaluated through two databases: Hammersmith dataset (for the normal scans) and MICCAI 2018 (for pathological MRI). Moreover, we extend our model to cope with noisy pathological MRI scans. The normalized mean square error (NMSE), the peak-to-noise ratio (PSNR), and the structural similarity index (SSIM) have been adopted as evaluation metrics in order to evaluate the proposed architecture performance and to make a comparative study with the state-of-the-art reconstruction algorithms. The higher PSNR and SSIM values as well as the lowest NMSE values could attest that the proposed architecture offers better reconstruction and preserves textural image details. Furthermore, the running time is about 0.8 s, which is suitable for real-time processing. Such results could encourage the neurologist to adopt it in their clinical routines. Graphical abstract.


Stunkardia minuta sp. n. (Trematoda: Paramphistomidae) from the Malayan box-tortoise Cuora amboinensis.
Stunkardia minuta sp. n. was recovered from the small intestine and rectum of 5 box-tortoises (Cuora amboinensis) in Malaysia. The average body size (L X W) is 11-42 X 2-35 mm; oral sucker 1-51 X 1.02; oral pouches 0-21 X 0.18; ventral sucker 1-67 X 1-43; oesophageal bulb 0-54 X 0-54; ant. testis 0-95 X 0-98; post. testis 0-94 X 0.94; seminal vesicle 0-82 X 0-24; ootype 0-21 X 0-41; ovary 0-41 X 0-34; and egg 121 X 83 micrometer. Although morphologically similar to S. dilymphosa, S. minuta is distinct from any other reported member of the Paramphistomidae.


Connection and distinction of tumor regression grading systems of gastrointestinal cancer.
As the neoadjuvant therapy has been successfully introduced in the treatment of gastrointestinal malignancies, the evaluation of therapeutic effectiveness is becoming increasingly important. Tumor-node-metastasis system has been widely applied. However, this system is mainly based on the location of residual tumor, but does not consider the amount of residual tumor. Tumor regression grading system, a quantitative method to assess the reaction of tumor to neoadjuvant treatment, could be used as a supplement to tumor-node-metastasis system and provide additional information on prognosis. To date, numerous gastrointestinal grading systems have been used in esophageal/esophagogastric junction carcinoma, gastric adenocarcinoma, colorectal cancer, and most of them were considered to associate with clinical outcomes. In this review, firstly, we expounded the importance of tumor regression grading systems, and summarized the histopathological changes after neoadjuvant therapy. Secondly, we introduced some commonly used gastrointestinal systems, as well as the relationships and nuance. Finally, we discussed pivotal issues about these systems. In this part, we explained the calculation methods based on grid points and square measures, discussed several factors leading to observer bias, containing the slice number and the grading tier number, and analyzed the factors that might affect clinical significance, covering anatomical location, the selection of survival index, and the tumor type. Tumor regression grade systems could be divided into two main classifications, the relative amount of fibrosis and residual tumor, and the proportion of residual tumor in the tumor bed. However, the definitions of these systems were still need to be improved. The tumor regression grading system is useful in evaluating tumor response to neoadjuvant therapy, but more work is needed to refine and unify the system.


Ethopharmacology of imipramine in the forced-swimming test: gender differences.
Most of the pre-clinical tests used to assay the efficacy of prospective new agents are done with male experimental animals. In this case, a large part of the population is disregarded as is the interaction of the new agent's effects with female hormonal fluctuations. The present study reviews the technical procedures characteristic for the forced-swimming test and the behavioral outcome induced by the testing procedure in males. It also compares the anti-immobility effects of the classic antidepressant imipramine (IMI) in male and female rats using a detailed behavioral scoring. Female rats had vaginal smears done before the beginning of the behavioral testing and were administered with three doses 24 h, 5 h and 1 h before the retest, as were male rats. Tests were videotape-recorded for analysis of the frequency and duration of the behaviors during forced-swimming. Male rats spend around 50% of the time immobile during the retest. There was a significant, dose-dependent decrease in immobility duration and a decrease in head-shakes of male rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior comprising 75% of the mobile behaviors. Females showed much lower immobility duration and head-shake frequency during the forced-swimming than males and spent longer periods in mobile behaviors. Imipramine only decreases immobility frequency and head-shakes of females, and increases the escape-type behavior of climbing, decreasing swimming in the middle of the tank. This effect is more noticeable during estrus and proestrus. These results demonstrate the main behavioral differences between males and females in the forced-swimming test. It also elucidates that the effects of imipramine are measurable in males using the duration of the behaviors, while the frequencies of behaviors are modified in females treated with imipramine.


Demonstration and partial purification of lactoperoxidase from human colostrum.
A peroxidase with stability, chromatographic and immunoreactive properties similar to that of bovine lactoperoxidase has been partly purified from human colostrum. Hydrophobic interaction chromatography on Phenyl-Sepharose C1-4B gave a 10-fold purification with an apparent recovery of about 45%. The enzyme was quantitatively and specifically adsorbed to beads of anti-lactoperoxidase (bovine)-Protein A-Sepharose. No adsorption of the enzyme was observed on immunoadsorbent columns prepared with high-titre polyclonal antibodies raised against human myeloperoxidase and human eosinophile peroxidase.


Radiation guidelines for gliomas.
Gliomas are the most frequent primary brain tumour. The proximity of organs at risk, the infiltrating nature, and the radioresistance of gliomas have to be taken into account in the choice of prescribed dose and technique of radiotherapy. The management of glioma patients is based on clinical factors (age, KPS) and tumour characteristics (histology, molecular biology, tumour location), and strongly depends on available and associated treatments, such as surgery, radiation therapy, and chemotherapy. The knowledge of molecular biomarkers is currently essential, they are increasingly evolving as additional factors that facilitate diagnostics and therapeutic decision-making. We present the update of the recommendations of the French society for radiation oncology on the indications and the technical procedures for performing radiation therapy in patients with gliomas.


Dynamic modification of poly(methyl methacrylate) chips using poly(vinyl alcohol) for glycosaminoglycan disaccharide isomer separation.
We describe a microchip electrophoresis (MCE) method for the assay of unsaturated disaccharides of chondroitin sulfates, dermatan sulfates, and hyaluronic acid (HA). Poly(vinyl alcohol) (PVA) could be irreversibly adsorbed onto poly(methyl methacrylate) (PMMA) substrates and this approach was applicable for dynamic coating. The characteristics of the PMMA surface with PVA coating were evaluated in terms of the wettability, EOF, and adsorption of 2-aminoacridone (AMAC)-labeled disaccharide. The water contact angle decreased from 73 degrees on a pristine PMMA surface to 37.5 degrees on a PVA-coated surface, indicating that the PVA coating increased hydrophilicity. EOF was reduced approximately twofold and was relatively stable. Scanning electron microscopy and fluorescence microscopy images showed that adsorption of AMAC-labeled disaccharides was dramatically suppressed. Using the PVA coating, baseline separation of two pairs of glycosaminoglycan (GAG) disaccharide isomers, DeltaDi-diS(B)/DeltaDi-diS(D) and DeltaDi-0S/DeltaDi-HA, was achieved in Tris-borate buffer within 130 s by MCE.


Thoracoscopic resection of intra- and extralobar pulmonary sequestration in the first 3 months of life.
Thoracoscopic techniques have gained increasing acceptance in pediatric surgery, but experience with newborns and small children is limited. To our knowledge, a series of minimally invasive resection of pulmonary sequestration in newborns has not yet been reported in the literature. We report on 5 patients with pulmonary sequestration thoracoscopically. From November 2000 to November 2002, 5 patients underwent thoracoscopic resection of pulmonary sequestration. Ages ranged from 4 to 91 days. Two patients had postnatal pulmonary symptoms. Preoperative diagnosis was dubious in 4 children. There were 4 extralobar and 1 intralobar pulmonary sequestrations. Thoracoscopy was performed with 3-mm instruments and 3 to 5 ports. All procedures were completed successfully. The median duration of the operation was 95 minutes (range, 63-117 minutes), and visualization was excellent. Anomalous blood vessels were clipped and/or ligated. Four patients were extubated immediately after the operation, 1, the day after. The postoperative course was uneventful in all children. At follow-up after 14 months (mean; range, 10-19 months), all patients were free of symptoms and had normal chest x-rays. Thoracoscopy is feasible for resection of intra- and extralobar pulmonary sequestrations during the first 3 months of life.


Pseudotumor of kidney.
Hypertrophy of the renal columns of Bertin may present as a mass, at times difficult to distinguish from neoplasia or cyst. Herein, we present a case characterized by the inability of this lesion to absorb 99mTc DTPA (99mTechnetium diethylenetriaminepentaacetic acid) isotope on two separate renal studies.


Utility of Smartphone Telemedical Consultations for Peritonsillar Abscess Diagnosis and Triage.
Telemedicine is rapidly gaining traction as a way to reduce costs and connect patients with medical experts outside their local communities. Peritonsillar abscess (PTA) is a logical pathologic condition to evaluate for effectiveness of remote diagnosis given its prevalence and the paucity of on-site otolaryngologists at many institutions. To explore the potential of otolaryngology telemedical consultation in triaging and diagnosing patients with suspected PTA. A comparative effectiveness research study was conducted from January 1 to June 30, 2018, at 3 tertiary care hospitals among 31 consecutive patients aged 18 to 85 years for whom the otolaryngology department was consulted to assess for PTA. Statistical analysis was conducted from July 1 to September 30, 2018. Telemedical evaluation of suspected PTA by 5 attending otolaryngologists blinded to patients' history aside from the chief report of odynophagia. Otolaryngologists rated each patient video on whether they believed the patient had a PTA and whether the case warranted prompt evaluation by an otolaryngologist. Predictions were compared with the criterion standard of drainage or negative needle aspiration. Otolaryngologists additionally assessed video quality. Rates of accurate diagnosis and triage of PTA based on otolaryngologists' review of oropharyngeal examinations recorded using standard smartphone cameras, as well as percentage of videos of oropharyngeal examinations using standard smartphone cameras deemed of sufficiently high quality for clinical decision-making. A total of 31 patients (16 women [51.6%]; mean age, 31.9 years [range, 18-62 years]) were recruited, and 16 patients (51.6%) had a PTA. Comparing otolaryngologists' predictions with PTA status by the criterion standard, the prediction was consistent with that of the criterion standard 81% of the time averaged across otolaryngologists (mean diagnostic accuracy, 0.81). Similarly, the mean diagnostic accuracy was 0.83 when comparing the otolaryngologist's suggestion for a prompt in-person evaluation with actual PTA status by the criterion standard. Comparing patients who were deemed to require prompt otolaryngology evaluation and those with PTA by the criterion standard, mean sensitivity was 90%. Videos were rated as of sufficiently high quality to make a diagnosis in 154 of 155 videos (99.4%). This study suggests that telemedical consultation is a viable, cost-conscious, efficient, and safe approach to PTA management. Despite having some difficulty diagnosing PTAs based on "history concerning for PTA" and oropharyngeal video alone, otolaryngologists are able to determine, with high sensitivity, which patients require prompt otolaryngology evaluation. The recording of consistently high-quality video using a standard smartphone camera is achievable without formal training.


cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner.
The calcium/calmodulin-dependent kinase that phosphorylates and inactivates eukaryotic elongation factor 2 (eEF2 kinase; eEF2K) is subject to multisite phosphorylation, which regulates its activity. Phosphorylation at Ser359 inhibits eEF2K activity even at high calcium concentrations. To identify the kinase that phosphorylates Ser359 in eEF2K, we developed an extensive purification protocol. Tryptic mass fingerprint analysis identified it as cdc2 (cyclin-dependent kinase 1). cdc2 co-purifies with Ser359 kinase activity and cdc2-cyclin B complexes phosphorylate eEF2K at Ser359. We demonstrate that cdc2 contributes to controlling eEF2 phosphorylation in cells. cdc2 is activated early in mitosis. Kinase activity against Ser359 in eEF2K also peaks at this stage of the cell cycle and eEF2 phosphorylation is low in mitotic cells. Inactivation of eEF2K by cdc2 may serve to keep eEF2 active during mitosis (where calcium levels rise) and thereby permit protein synthesis to proceed in mitotic cells. Amino-acid starvation decreases cdc2's activity against eEF2K, whereas loss of TSC2 (a negative regulator of mammalian target of rapamycin complex 1(mTORC1)) increases it. These data closely match the control of Ser359 phosphorylation and indicate that cdc2 may be regulated by mTORC1.


Excess healthcare expenditure in adults treated for solid cancer in childhood: a cohort study in France.
Due to late effects, childhood cancer survivors (CCS) are more likely to have multiple chronic conditions than the general population. However, little is known about the economic burden of care of CCS in the long term. To estimate excess healthcare expenditure for long-term CCS in France compared to the general population and to investigate the associated factors. We included 5353 5-year solid CCS diagnosed before the age of 21 years before 2000 from the French CCS cohort and obtained a random reference sample from the general population for each CCS, matched on age, gender and region of residence. We used the French national health data system to estimate annual healthcare expenditure between 2011 and 2018 for CCS and the reference sample, and computed the excess as the net difference between CCS expenditure and the median expenditure of the reference sample. We used repeated-measures linear models to estimate associations between excess healthcare expenditure and CCS characteristics. Annual mean (95% CI) excess healthcare expenditure was €3920 (3539; 4301), mainly for hospitalization (39.6%) and pharmacy expenses (17%). Higher excess was significantly associated with having been treated before the 1990s and having survived a central nervous system tumor, whereas lower excess was associated with CCS who had not received treatment with radiotherapy. Of the variables that influence excess healthcare expenditure, a lever for action is the type of treatment administered. Future research should focus on addressing the long-term cost-effectiveness of new approaches, especially those related to radiotherapy.


Transcriptome analysis of Procambarus clarkii infected with infectious hypodermal and haematopoietic necrosis virus.
Infectious hypodermal and haematopoietic necrosis virus (IHHNV) is a major viral pathogen in cultured penaeid shrimp. IHHNV has many hosts, mainly including crustaceans. It has recently been reported that Procambarus clarkii can be infected by IHHNV. In the present study, we studied the hepatopancreas of P. clarkii by transcriptome high-throughput sequencing to analyze the response of P. clarkii to IHHNV infection. After de novo assembly, there were 400,340,760 clean reads. A total of 237 differentially expressed genes (DEGs) were obtained, including 77 significantly up-regulated unigenes and 160 significantly down-regulated ones. The expression levels of 12 immune-related DEGs were validated by qRT-PCR, substantiating the reliability of RNA-Seq results. The enrichment analysis of DEGs showed that the immune-related pathways were closely related to apoptosis and phagocytosis. Moreover, a large number of pathways related to metabolic function were down-regulated, suggesting that IHHNV infection might affect the growth of P. clarkii.


Helical supramolecular assemblies of {2,4,6-[Cp*Rh(E2-1,2-C2B10H10)(NC5H4CH2S)]3(triazine)} (E = S, Se) shaped by Cp*-Toluene-Cp* pi-stacking forces and BH-pyridine hydrogen bonding.
Polycarborane-substituted molecules [Cp*Rh{E 2C 2(B 10H 10)}] 3(tpst) [E = S ( 2a), Se ( 2b)] were synthesized and characterized. 2a and 2b form toluene solvates in the solid state showing infinitely connected [( 2a, b)-(toluene)] infinity helices. The chains of these supramolecules are held together by Cp*-toluene-Cp* pi-stacking interactions of two of the three Cp* ligands of the bell-shaped 2a and 2b molecules. Unconventional BH (delta-)-pyridyl (delta+) aromatic hydrogen bonding enforces the bell-shapes of the molecular units, and the Cp* conformations are expected to induce the supramolecular structures.


The emergence and evolution of the expression "conflict of interests" in science: a historical overview, 1880--2006.
The tendency is strong to take the notion of "conflict of interests" for granted as if it had an invariant meaning and an ethical content independent of the historical context. It is doubtful however, from an historical and sociological point of view, that many of the cases now considered as instances of "conflicts of interests" would also have been conceived and perceived as such in, say, the 1930s. The idea of a "conflict of interests" presupposes that there are indeed interests in conflict. Conversely, as long as there is a consensus among the different groups involved, they will not conceive and even less denounce a given practice as being an instance of a "conflict of interests". In this article we will show that the content of the discussions over conflicts of interests has changed over time in close relation with the transformations of the research system. In other words: there are social conditions for the emergence of "conflicts of interests". The changing meaning of the notion is assessed by analyzing the presence of the expression "conflicts of interests" in the magazine Science over the past century. Three different meanings emerge and their content has evolved in close link with the changing structure of the relations between the scientific community first with the State and then with industry. It moved from a situation external to the scientific community to a debate going on inside the scientific community generated by the growing relations between university and industries.


The first enantioselective synthesis of the amino acid, (2S,3S,4R)-gamma-hydroxyisoleucine using a palladium(II) catalysed 3,3-sigmatropic rearrangement.
A synthetic route towards the synthesis of (2S,3S,4R)-gamma-hydroxyisoleucine, the amino acid component of the natural product, funebrine has been developed using as the key step, a palladium(II) catalysed 3,3-sigmatropic rearrangement to create the (2S)-stereogenic centre.


Schizophrenia, neuroimaging and connectomics.
Schizophrenia is frequently characterized as a disorder of brain connectivity. Neuroimaging has played a central role in supporting this view, with nearly two decades of research providing abundant evidence of structural and functional connectivity abnormalities in the disorder. In recent years, our understanding of how schizophrenia affects brain networks has been greatly advanced by attempts to map the complete set of inter-regional interactions comprising the brain's intricate web of connectivity; i.e., the human connectome. Imaging connectomics refers to the use of neuroimaging techniques to generate these maps which, combined with the application of graph theoretic methods, has enabled relatively comprehensive mapping of brain network connectivity and topology in unprecedented detail. Here, we review the application of these techniques to the study of schizophrenia, focusing principally on magnetic resonance imaging (MRI) research, while drawing attention to key methodological issues in the field. The published findings suggest that schizophrenia is associated with a widespread and possibly context-independent functional connectivity deficit, upon which are superimposed more circumscribed, context-dependent alterations associated with transient states of hyper- and/or hypo-connectivity. In some cases, these changes in inter-regional functional coupling dynamics can be related to measures of intra-regional dysfunction. Topological disturbances of functional brain networks in schizophrenia point to reduced local network connectivity and modular structure, as well as increased global integration and network robustness. Some, but not all, of these functional abnormalities appear to have an anatomical basis, though the relationship between the two is complex. By comprehensively mapping connectomic disturbances in patients with schizophrenia across the entire brain, this work has provided important insights into the highly distributed character of neural abnormalities in the disorder, and the potential functional consequences that these disturbances entail.


[The hepatitis C virus among the prison population of Valencia].
To know the prevalence of anti-VHC in the Valencia Male Penitentiary Centre. A prospective study in which a representative sample of the inmates is included. In each case the anti-VHC and the ALT are studied. Serological results were correlated with history of intravenous drug addiction, alcohol abuse and duration and number of internments. INMATES: 750 inmates are included; they represent 41% of the people interned in this Centre during 1991. A high prevalence (45%) of the serological marker for VHC infection was observed. The prevalence of anti-VHC+ among the drug addict inmates is around 90% and this situation was already found during the first year of drug addiction. Among non-drug addict inmates the prevalence is 14%. Hepatitis C virus infection has a correlation with the duration and number of internments; 75% of the inmates with high ALT values have anti-VHC+. Nearly half of the inmates are infected with hepatitis C virus. The drug addict inmates are infected during the first year of their habit. The majority of the inmates with elevated ALT has anti-VHC+.


Replantation of the testis: report of a case.
To our knowledge there has been no report to date of successful testis replantation after complete traumatic severance of the funiculus within the scrotum. We report a case in which both funiculi were cut completely (one of which was severed 0.8 cm. proximal to the upper pole of the testis, and the other just at the junction of the funiculus and the testis). We successfully rejoined the testis with the funicular stump to the proximal cut end of the right side using a microsurgical technique. The total ischemia period of the replanted testis was 6 hours. The penis was erect 4 days postoperatively and blood testosterone level was within the normal range. At testicular biopsy 120 days postoperatively the germ cells could be seen in various stages of development and the appearance of the Leydig cells was normal.


Detection and genotyping of Cryptosporidium spp. in large Japanese field mice, Apodemus speciosus.
The genus Cryptosporidium, which is an obligate intracellular parasite, infects various vertebrates and causes a diarrheal disease known as cryptosporidiosis. Wild rodents are naturally infected with zoonotic Cryptosporidium; thus, they are potential reservoirs of the parasites. Mice are common rodents frequently found in agricultural areas and have many opportunities to contact other wild animals, livestock, and humans. Irrespective of the potential risk, there are few epidemiologic studies of Cryptosporidium in wild mice because of their low economic importance and the difficulty in conducting surveys. Hence, the species and genotypes of Cryptosporidium in wild mice living around various areas remain unclear. We investigated the species and genotype distribution and prevalence of Cryptosporidium in the large Japanese field mouse (Apodemus speciosus) in an agricultural site in Osaki, Miyagi Prefecture, Japan. In total, 15 mice were captured and examined in this study. By microscopic analysis, only one mouse (JFM 3) was determined to be Cryptosporidium-positive, while the parasite were detected in four mice (JFM 3, 6, 10, and 15) by a molecular approach using partial SSU rRNA gene sequences. Based on nucleotide sequence and phylogenetic analysis, the Cryptosporidium isolates were identified as C. ubiquitum (from JFM 10) and C. muris (from JFM 3 and 6). In contrast, the Cryptosporidium in JFM 15 was not identified as a known species or genotype and is therefore proposed as a novel genotype; the Naruko genotype. More molecular data are necessary to elucidate the taxonomic identity of this novel Cryptosporidium genotype. The C. muris Japanese field mouse genotypes showed marked divergence compared to that in a previous report. The large Japanese field mouse might thus represent a reservoir of multiple Cryptosporidium spp.


2,8-Dimesitylboranyl-6H,12H-5,11-methano-dibenzo[b,f][1,5]diazo-cine.
In the title compound, C(51)H(56)B(2)N(2), a substituted Tröger's base, the dihedral angle between the two benzene rings constituting the Tröger's base framework is 104.42 (6)°. The crystal structure is stabilized by C-H⋯π and weak C-H⋯N inter-actions.


Monoclonal antibodies reactive with glioma cell lines derived from experimental brain tumors.
The production of hybridomas between X63-Ag8.653 myeloma cells and spleen cells from female BALB/c mice immunized with 79FR-G-41 glioma cells is reported. One hundred and six hybridoma clones were obtained secreting monoclonal antibodies (McAbs) against different target cells. Specificity tests (RIA, micro-ELISA) showed that McAbs produced by three hybridoma clones (13GC1, 14BC1, 14FC3) bound 79FR-G-41 glioma cells but did not react with fibroblasts, kidney and brain cells of newborn F344 rats. From the specificity analysis of two McAbs (13GC1, 14BC1) it is evident that these did not only react with 79FR-G-41 cells but also with other glioma cell lines (78FR-G-219, 78FR-G-284, 78FR-G-299 and 78FR-G-344) established from chemically induced rat brain gliomas. These results suggest, in accordance with the findings in human neuroectodermal tumors, the expression of common reactivity antigens in different brain tumors of glial origin. However, the McAbs obtained against experimental rat glioma cells did not recognize glioma cells derived from spontaneous brain tumors of dog or man. Immunofluorescence and immunoperoxidase tests indicate that there is a remarkable heterogeneity among cells of experimental glioma lines with respect to the expression of glioma associated determinants recognized by McAbs. The fact that only a variable number instead of the totality of tumor cells in any asynchronous and uncloned tumor cell population expresses, at a certain time, recognizable antigenic determinants has to be taken into account, particularly if they are considered to be employing McAbs as carrier molecules for diagnostic and therapeutic purposes.


An exposure-assessments strategy accounting for within- and between-worker sources of variability.
A strategy is presented for comparing exposures to an occupational exposure limit (OEL) and for suggesting appropriate interventions when exposures are unacceptable. The major departure from previous approaches is the explicit recognition that exposures vary both within and between workers in a given occupational group. The primary goal is to determine whether the probability of overexposure is acceptably small (a value of 0.10 or less is recommended), with overexposure being defined as the likelihood that a randomly selected worker's true mean exposure exceeds the OEL. The exposure-assessment protocol contains five levels. It is suggested that at least two shift-long measurements be randomly collected from each of 10 workers for preliminary analysis. If the logged exposure data appear to be appropriate for testing (Level 1), the probability of overexposure is compared to the pre-determined value via a rigorous test of statistical significance (Level 2). Based upon published data, this test is likely to classify exposures as acceptable with 20 measurements when the group mean exposure is less than one-fifth of the OEL. However, if exposure is found to be unacceptable, re-sampling can be considered to increase the power of the test (Level 3). Otherwise, it is necessary to reduce exposures and then to re-apply the protocol. If it appears that all persons in the group have essentially the same predicted mean exposures (Level 4), then engineering or administrative controls are recommended. If, on the other hand, substantial differences appear to exist amongst these predicted mean values, regrouping and/or modifications of tasks and work practices should be considered (Level 5). Application of the protocol is illustrated with samples of data from four groups of workers exposed to inorganic nickel in the nickel-producing industry.


Application of Box-Wilson experimental design method for the photodegradation of bakery's yeast industry with UV/H2O2 and UV/H2O2/Fe(II) process.
Decolorization and mineralization of bakery's yeast industry effluent by photochemical advanced oxidation processes (AOPs) utilizing UV with hydrogen peroxide and Photo-Fenton, were investigated in a laboratory scale photo-reactor equipped with a 16 W low-pressure mercury vapor lamp. The Box-Wilson experimental design method was employed to evaluate the effects of major process variables (e.g. pH, oxidant dose, and irradiation time) on the decolorization efficiency. Response function coefficients were determined by regression analysis of the experimental data and prediction results agreed with the experimental results. The optimum hydrogen peroxide concentration and irradiation time were found to be 5 mM and 50 min at pH 3, respectively, for UV/H2O2 process. In the Photo-Fenton process application, maximum decolorization efficiency (96.4%) was obtained at the optimum reaction conditions that were 100 mM H2O2 and 1 mM Fe(II) doses at pH 3, and 10 min of irradiation time.


Subcellular localization and partial characterization of insulin proteolytic activity in rat liver.
Using (A14-125I)-insulin as a tracer, insulin proteolytic activity in rat liver was found to be localized both to the cytosol and the endoplasmic reticulum. The membrane-associated activity was highly latent (70-80%). Both cytosolic and particulate activities had similar Km values and Mr of approx. 300 000 by gel filtration. Both were strongly inhibited by diamide (90%), but were unaffected by leupeptin or pepstatin. A comparison of the subcellular distributions with various 125I-isomers of insulin as tracers showed that both particulate and cytosolic activities were highest with (A14-125I)-insulin.


UV-inducible DNA repair in Acinetobacter calcoaceticus.
Bacterial mutation frequency after UV irradiation and phage mutation frequency under conditions of W-reactivation were determined in A. calcoaceticus. With the exception of streptomycin resistance, there was no increase in the frequency of the assayed markers above the background level. The increased survival of phage during W-reactivation was not followed by an increase in the frequency of mutation from turbid to clear plaque formers among phage survivors. The findings suggested that the UV-inducible repair pathway in A. calcoaceticus was error free. Post-irradiation incubation of UV-treated culture before phage infection resulted in a further increase of W-reactivation. As chloramphenicol inhibited this response, it was concluded that de novo protein synthesis was involved in the UV-inducible repair pathway in A. calcoaceticus.


Causal Relations Between Obstructive Sleep Apnea and Stroke: A Mendelian Randomization Study.
Previous studies of obstructive sleep apnea (OSA) in relation to stroke have been noted. However, the exact causality remains to be clearly defined. We aimed to adopt a two-sample Mendelian randomization study to investigate the causal effects of OSA on stroke and its subtypes. A two-sample Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of OSA on stroke and its subtypes, including, based on publicly genome-wide association studies (GWAS) databases. The inverse variance weighted (IVW) method was used as the main analysis. MR-Egger regression, weighted mode, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed methods and were adopted as supplementary analysis to ensure the robustness of the results. Genetically predicted OSA was not related to the risk of stroke (odds ratio (OR), 0.99, 95% CI, 0.81-1.21, p = 0.909), and its subtypes, ischemic stroke (IS) (OR, 1.01, 95% CI, 0.82-1.23, p = 0.927), large vessel stroke (LVS) (OR, 1.05, 95% CI, 0.73-1.51, p = 0.795), cardioembolic stroke (CES) (OR, 1.03, 95% CI, 0.74-1.43, p = 0.855), small vessel stroke (SVS) (OR, 1.13, 95% CI, 0.88-1.46, p = 0.329), lacunar stroke (LS) (OR, 1.07, 95% CI, 0.74-1.56, p = 0.721) as well as intracerebral hemorrhage (ICH) (OR, 0.37, 95% CI = 0.09, 1.48, p = 0.160) (Wald ratio method). Other supplementary MR methods also confirmed similar results. There may be no direct causal relationship between OSA and stroke or its subtypes.


Biomarkers of PAH exposure and hematologic effects in subjects exposed to combustion emission during residential (and professional) cooking practices in Pakistan.
The aim of this study was to evaluate and compare the exposure of household women and professional male workers to combustion emission in the indoor and semi-outdoor environments, respectively, by using biochemical parameters and the biomarkers of exposure to polycyclic aromatic hydrocarbon (PAH). Female (WR n = 60) and male "cooks" (WC n = 60) exposed to the combustion emission of fuel wood and coal in rural/suburban areas of Pakistan were recruited in this study and compared to non-exposed female (CF) and male (CM) groups (n = 32 and 34, respectively). Urinary biomarkers of PAH exposure including 1-hyroxypyrene (1-OHPyr), α-naphthol, and β-naphthol were analyzed together with the biomarkers of effect, including the serum c-reactive proteins (CRP), white blood cells (WBCs), hemoglobin (Hb), red blood cells (RBC), and platelet (PLT) count. In addition, blood superoxide dismutase (SOD) and urinary level of 8-hydroxydeoxyguanosine (8-OHdG) were evaluated to determine the oxidative stress and DNA damage, respectively. A questionnaire was used to document demographic-, health-, and exposure-related information. The results showed that urinary β-naphthol was almost 44% higher in WR subjects than WC (median 7.69 vs. 3.39 μmol/mol-Cr, respectively; p = 0.01) and respective controls (CF). Higher urinary 8-OHdG were observed in WR (71.1 ng/mg-Cr) than WC (56.37 ng/mg-Cr) (p < 0.001), and lower life status and higher degree of headache were observed in WR than WC. In WCs, however, a low Hb and high WBC (8.29 × 10(3) μL(-1), ranging between 6.1 and 10.6 × 10(3) μL(-1)) were observed in comparison with CM. The study shows that WC subjects used larger amount of fuel and were subjected to prolonged exposure. It was concluded that the role of ventilation is fundamental and WR were more exposed to PAHs despite the fact that WC spent more time in cooking (due to occupational requirement) than WR.


Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction.
Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI.


Helper activity for antibody synthesis encoded by mRNA extracted from human peripheral blood mononuclear cells.
Translation products in Xenopus laevis of mRNA from human peripheral blood mononuclear cells were tested for their capacity to replace T cells in the anti-SRBC response of nude spleen cells. When the starting material came from PHA or FCS-stimulated lymphocytes, the translated lymphokines, displaying such a B cell helper activity were found to be encoded by mRNA sedimenting at 6-7S and 13S on a sucrose density gradient. 6-7S mRNA from control, non-stimulated lymphocytes was also able to code for B cell helper activity. Thorough T-cell depletion of mouse responder cell populations left unchanged the activity of 6-7S mRNA products while preventing that of 13S products. The latter were found to contain IL-2, which suggests that their action on B cells was indirect, mediated by T-cell stimulation.


Economic and long-term benefits of ribavirin therapy on respiratory syncytial virus infection.
Ribavirin is a broad-spectrum antiviral agent. Administered as an aerosol, it has been shown to be clinically effective in improving the signs and symptoms of viral bronchiolitis in infancy, particularly cases due to respiratory syncytial virus (RSV). This paper reviews the evidence for economic and/or long-term clinical benefits from using ribavirin in the acute illness. There are data to suggest that use of ribavirin may lead to a reduction in therapeutic interventions and duration of hospital stay, with associated savings in hospital costs. Ribavirin reduces the production of RSV-specific IgE, and (in vitro) inhibits the release of inflammatory mediators from mast cells, suggesting that there could be beneficial effects on the incidence of postbronchiolitis wheezing. Confirmatory studies are in progress.


Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19.
The medicinal potential of marine invertebrates' bioactive components that may act as anti-COVID-19 demonstrated promising results. Ophiocoma dentata, which is common in the Red Sea, is one such source. Therefore, this study aimed to isolate a new compound from the brittle star, Ophiocoma dentata, and evaluate its efficacy as anti-COVID-19 in-silico and in-vitro. Standard procedures were followed in order to assess the isolated compound's preliminary toxicity and anti-inflammatory properties. Computer virtual screening technology through molecular docking and ADMET studies was conducted as well as a new steroid derivative was isolated for the first time, named 5α-cholesta-4(27), 24-dien-3β, 23 β-diol. Investigation of the Anti-Covid-19 activity of the isolated compound using a Plaque reduction assay revealed 95% inhibition at a concentration of 5 ng/µl (12.48 µM). Moreover, this compound showed an IC50 of 11,350 ± 1500 ng/ml against the normal fibroblast cells, indicating its safety. Interestingly, this compound exhibited anti-inflammatory activity with an IC50 of 51.92 ± 0.03 μg/ml compared to a reference drug's IC50 of 53.64 ± 0.01 μg/ml, indicating that this compound is a potent anti-inflammatory. In silico data have proved that the isolated compound is a promising viral inhibitor against SARS-CoV2 and is thus recommended as a future nature preventive and curative antiviral drug.


Modeling transmission of directly transmitted infectious diseases using colored stochastic Petri nets.
In order to improve our understanding of directly transmitted pathogens within host populations, epidemic models should take into account individual heterogeneities as well as stochastic fluctuations in individual parameters. The associated cost results in an increasing level of complexity of the mathematical models which generally lack consistent formalisms. In this paper, we demonstrate that complex epidemic models could be expressed as colored stochastic Petri nets (CSPN). CSPN is a mathematical tool developed in computer science. The concept is based on the Markov Chain theory and on a standard well codified graphical formalism. This approach presents an alternative to other computer simulation methods since it offers both a theoretical formalism and a graphical representation that facilitate the implementation, the understanding and thus the replication or modification of the model. We explain how common concepts of epidemic models--such as the incidence function--can be easily translated into an individual based point of view in the CSPN formalism. We then illustrate this approach by using the well documented susceptible-infected model with recruitment and death.


Pluripotent pig embryonic stem cell lines originating from in vitro-fertilized and parthenogenetic embryos.
Here, we report in vivo developmental competent pig embryonic stem cells (ESCs) originating from in vitro-fertilized and parthenogenetic embryos cultured in chemically defined culture media. The pig ESC lines expressed pluripotency markers and were capable of forming teratomas following subcutaneous injection into nude mice. These cell lines would be a useful resource for comparative developmental biology and agricultural biotechnology.


The genome of Symbiodiniaceae-associated Stutzerimonas frequens CAM01 reveals a broad spectrum of antibiotic resistance genes indicating anthropogenic drift in the Palk Bay coral reef of south-eastern India.
An increase in antibiotic pollution in reef areas will lead to the emergence of antibiotic-resistant bacteria, leading to ecological disturbances in the sensitive coral holobiont. This study provides insights into the genome of antibiotics-resistant Stutzerimonas frequens CAM01, isolated from Favites-associated Symbiodiniaceae of a near-shore polluted reef of Palk Bay, India. The draft genome contains 4.67 Mbp in size with 52 contigs. Further genome analysis revealed the presence of four antibiotic-resistant genes, namely, adeF, rsmA, APH (3")-Ib, and APH (6)-Id that provide resistance by encoding resistance-nodulation-cell division (RND) antibiotic efflux pump and aminoglycoside phosphotransferase. The isolate showed resistance against 73% of the antibiotics tested, concurrent with the predicted AMR genes. Four secondary metabolites, namely Aryl polyene, NRPS-independent-siderophore, terpenes, and ectoine were detected in the isolate, which may play a role in virulence and pathogenicity adaptation in microbes. This study provides key insights into the genome of Stutzerimonas frequens CAM01 and highlights the emergence of antibiotic-resistant bacteria in coral reef ecosystems.


Necessity of routine perioperative epidural catheter placement in laparoscopic colorectal resections: a retrospective data analysis.
Whether epidural anesthesia leads to further improvement in the postoperative course of colorectal procedures is under discussion. The aim of this study was to evaluate the effects of minimally invasive colorectal oncological interventions without epidural anesthesia (EDA). This retrospective data analysis included the clinical data of all patients who underwent minimally invasive oncological colorectal resection at our clinic between January 2013 and April 2019. Of 385 patients who met the inclusion criteria, 183 (group I; 47.5% of 385) received EDA, and 202 (group II; 52.5% of 385) received transversus abdominis plane block instead. The relevant target parameters were evaluated and compared between the groups. The postoperative complications were graded according to the Clavien-Dindo classification. The patients in group I (n=183; women, 77; men, 106; age 66.8 years) were younger (p=0.0035), received a urinary catheter more often (99.5% versus [vs.] 28.2% p<0.001), required longer, more frequent arterenol treatment (1.1 vs. 0.6 days; p<0.001), and had a longer intermediate care unit stay than those in group II (2.8 vs. 1.1 days; p<0.001). Postoperative pain levels were not significantly different between the groups (p=0.078). The patients in group I were able to ambulate later than those in group II (4 vs. 2 days; p<0.001). The difference in the postoperative day of the first defecation was not significant between the groups (p=0.236). The incidence of postoperative complications such as bleeding (p=0.396), anastomotic leaks (p=0.113), and wound infections (p=0.641) did not differ between the groups. The patients in group I had significantly longer hospital stays than those in group II (12.2 vs. 9.4 days; p<0.001). EDA can be safely omitted from elective minimally invasive colorectal resections, and its omission is not accompanied by any relevant disadvantages to the patient.


Prediction-error signals to violated expectations about person identity and head orientation are doubly-dissociated across dorsal and ventral visual stream regions.
Predictive coding theories of perception highlight the importance of constantly updated internal models of the world to predict future sensory inputs. Importantly, such theories suggest that prediction-error signalling should be specific to the violation of predictions concerning distinct attributes of the same stimulus. To interrogate this as yet untested prediction, we focused on two different aspects of face perception (identity and orientation) and investigated whether cortical regions which process particular stimulus attributes also signal prediction violations with respect to those same stimulus attributes. We employed a paradigm using sequential trajectories of images to create perceptual expectations about face orientation and identity, and then parametrically violated each attribute. Using MEG data, we identified double dissociations of expectancy violations in the dorsal and ventral visual streams, such that the right fusiform gyrus showed greater prediction-error signals to identity violations than to orientation violations, whereas the left angular gyrus showed the converse pattern of results. Our results suggest that perceptual prediction-error signalling is directly linked to regions associated with the processing of different stimulus properties.


Topographical distribution of ATP in rat brain.
Studies on the distribution of ATP in microdissected segments of the rat brain indicate that the nucleotide is concentrated in gray matter, and especially in the thalamus, hippocampus, entorhinal cortex and sensorimotor cortex. These distribution studies in conjunction with previous neuropharmacological studies, support the concept that adenine nucleotides may function as intercellular mediators in various regions of the brain.


Outcome of Tracheostomy in COVID-19 Patients.
Since the start of the COVID-19 pandemic 2019, quite a few patients became critical and needed ICU admission with ventilator assistance. Tracheostomy, which was initially performed late during the course of patient on ventilator, has now been considered a procedure that can be performed relatively early as this leads to early weaning of patients and overcomes the shortage of critical beds. This study aims to focus on the outcomes of tracheotomised COVID-19 patients in terms of survival and any tracheostomy related morbidity. A prospective study was performed on COVID-19 patients undergoing tracheostomy at this tertiary care teaching hospital, which also was a dedicated centre for treating COVID-19 patients. The duration of this study was from April 2020 to September 2021. Following tracheostomy, all patients were followed up regularly and clinical changes were recorded. Points that were specifically noted were timing of the tracheostomy, change in ventilator settings, tracheostomy related complications, requirement of oxygen, days needed to wean the patient, decanulation, and, if death, the cause of death. A total of 136 surgical open tracheostomies were performed on COVID-19 patients over the study period. The mean duration of intubation (timing of tracheostomy) was 12 days. A total of 73 out of 136 (53.6%) patients survived. 51 patients (37.5%) got decannulated during the course of the hospital stay. 9 patients were decanulated during the follow up visits and 13 patients were lost to follow up. 63 out of 136 (46.3%) patients died due to COVID pneumonia. Most of the patients who died had gone into multi-organ failure. Air leak syndromes (pneumothorax and pneumomediastinum) were common findings. 10 patients already had surgical emphysema before taking up for tracheostomy and 6 developed 2-3 days after tracheostomy. The most common complication was bleeding, which was seen in 28 out of 136 patients. The Median weaning of period of patients who survived was 5 days. Performing tracheostomy early in COVID-19 patients helps in early weaning of the patient from the ventilator and makes nursing care easier and increases the availability of ICU beds. The mortality rate was 46% amongst the 136 tracheostomies done in COVID-19 patients. Local site bleeding was the most common complication and surgical emphysema was also seen more than routine tracheostomies. The online version contains supplementary material available at 10.1007/s12070-022-03248-1.


Production and application of LPA polyclonal antibody.
By using colloidal gold as a hapten carrier, a kind of antibody against lysophosphatidic acid (LPA) was developed and used to successfully detect 500 ng/mL LPA in dot immunogold filtration assay. Such application of the LPA antibody could offer us a way to diagnose ovarian cancer at its early stage.


[N-acetylcysteine (NAC) inhibited pulmonary fibrosis in acute respiratory distress syndrome (ARDS)].
To investigate the effect of NAC treatment on lipopolysaccharide (LPS) treated human embryonic lung fibroblasts (HELF), in regard to oxidant injury and changes in indexes related to pulmonary fibrosis in ARDS. Four groups of cultured HELF were treated with: vehicle, LPS(1 pg/ml), NAC (1 mmol/L)+LPS (1 pg/ml) and dexamethasone (DEX, 1 pmol/L)+LPS (1 pg/ml) for 24 hours. The content of collagen and the γ-glutamylcysteinylglycine (GSH) in the cells were determined. As compared to the control group, the collagen content (pg/mg: 78.97+1.79 vs. 72.90+1.70)and GSH content (pg/mg: 23. 27 0. 92 vs. 26. 34+ 0. 83) in LPS group were significantly (P<0. 05) higher and lower, respectively; NAC and DEX both suppressed the effect of LPS on collagen content (72. 23 ± 1.35, 73.64 1.89 vs. 78.97 + 1.79); and GSH content (26.52 0.62, 25.85 ± 0.60 vs. 23.27+ 0.92)significantly (P < 0. 05 or P < 0. 01) in the treated cells. No significant difference was found between NAC+LPS and DEX+LPS group, either in the content of collagen or GSH. NAC can inhibit oxidant injury and pulmonary fibrosis in ARDS.


Production of soluble methane monooxygenase during growth of Methylosinus trichosporium on methanol.
Soluble methane monooxygenase (sMMO) can degrade many chlorinated and aromatic pollutants. It is produced by certain methanotrophs such as Methylosinus trichosporium when grown on methane under copper limitation but, due to its low aqueous solubility, methane cannot support dense biomass growth. Since it is water soluble, methanol may be a more attractive growth substrate, but it is widely believed that sMMO is not produced on methanol. In this study, when the growth-limiting substrate was switched from methane to methanol, in the presence of the particulate MMO inhibitor, allylthiourea, growth of M. trichosporium OB3b continued unabated and sMMO activity was completely retained. When allylthiourea was then removed, sMMO activity was maintained for an additional 24 generations, albeit at a slightly lower level due to the presence of 0.70 microM of Cu(2+) in the feed medium. While a biomass density of only 2 g l(-1) could be obtained on methane, 7.4 g l(-1) was achieved by feeding methanol exponentially, and 29 g l(-1) was obtained using a modified feeding strategy employing on-line carbon dioxide production measurement. It was concluded that methanol can be employed to produce large amounts of M. trichosporium biomass containing sMMO.


Sensitivity enhancement of remotely coupled NMR detectors using wirelessly powered parametric amplification.
A completely wireless detection coil with an integrated parametric amplifier has been constructed to provide local amplification and transmission of MR signals. The sample coil is one element of a parametric amplifier using a zero-bias diode that mixes the weak MR signal with a strong pump signal that is obtained from an inductively coupled external loop. The NMR sample coil develops current gain via reduction in the effective coil resistance. Higher gain can be obtained by adjusting the level of the pumping power closer to the oscillation threshold, but the gain is ultimately constrained by the bandwidth requirement of MRI experiments. A feasibility study here shows that on a NaCl/D(2) O phantom, (23) Na signals with 20 dB of gain can be readily obtained with a concomitant bandwidth of 144 kHz. This gain is high enough that the integrated coil with parametric amplifier, which is coupled inductively to external loops, can provide sensitivity approaching that of direct wire connection.


The impact of age on reproductive potential: lessons learned from oocyte donation.
Oocyte donation allows a unique opportunity to separately study the effect of aging on uterine receptivity and oocyte quality. The purpose of this report is to review the published experience on reproductive aging in both laboratory animals and humans as it pertains to oocyte and embryo donation. A review of the published medical literature. Natural fertility rates decline in most animals with age, becoming dramatically apparent in women as they enter the fifth decade of life. By the time of the perimenopause, pregnancy rarely occurs, whether or not assisted reproductive techniques are initiated. However, if oocytes are donated by young women to older women, both embryo implantation and pregnancy rates are restored to normal levels in recipients. These results strongly suggest the pregnancy wastage experienced by older women is largely a result of degenerative changes within the aging oocyte, rather than senescent changes in the uterus. The poor prognosis for fertility in older women can be reversed through oocyte donation from younger individuals.


Bilateral congenital absence of the anterior cruciate ligament associated with bilateral knee and hip osteoarthritis: Case report.
Congenital absence of the cruciate ligaments is very rare condition. Its association with congenital abnormalities of the spine, knee and hip, has been rarely reported. Most of the case reports were mostly reported before adolescence, so reports of the progression of this congenital disease at old age were extremely rare. A 65-year-old woman had a 7-year history of both knee and hip pain. On physical examination, valgus and varus instability on both knees and painful limitation of motion in both hip joints were observed. Radiography and magnetic resonance imaging showed the absence of the anterior cruciate ligament with osteoarthritis on both knees and hip osteoarthritis. Total knee and hip arthroplasties were performed on both knee joints and total hip arthroplasty. The pain and instability of both knees and hips were lost for follow up of more than a year, and the patient is doing well in daily life. Congenital absence of cruciate ligament may progress to osteoarthritis, do early detection and proper management is needed. In the treatment of older aged patients. Reports of treatment for this disorder are also very rare in older age. In old age, arthroplasty can be a useful treatment when the severe osteoarthritis is accompanied by instability. Since the congenital absence of the ACL in old age could lead to hip and knee osteoarthritis, periodic follow-up is necessary and arthroplasty can be a useful treatment when the severe osteoarthritis is accompanied by instability.


D2 but not D1 dopamine receptor stimulation augments brain signaling involving arachidonic acid in unanesthetized rats.
Signal transduction involving the activation of phospholipase A2 (PLA2) to release arachidonic acid (AA) from membrane phospholipids, when coupled to dopamine D1- and D2-type receptors, can be imaged in rats having a chronic unilateral lesion of the substantia nigra. It is not known, however, if the signaling responses occur in the absence of a lesion. To determine this, we used our in vivo fatty acid method to measure signaling in response to D1 and D2 receptor agonists given acutely to unanesthetized rats. [1-(14)C]AA was injected intravenously in unanesthetized rats, and incorporation coefficients k* for AA (brain radioactivity/integrated plasma radioactivity) were measured using quantitative autoradiography in 61 brain regions. The animals were administered i.v. the D2 receptor agonist, quinpirole (1 mg kg(-1), i.v.), the D1 receptor agonist SKF-38393 (5 mg kg(-1), i.v.), or vehicle/saline. Quinpirole increased k* significantly in multiple brain regions rich in D2-type receptors, whereas SKF-38393 did not change k* significantly in any of the 61 regions examined. In the intact rat brain, D2 but not D1 receptors are coupled to the activation of PLA2 and the release of AA.


Endometrial cancer and its precursors: a comparison of histological and clinical features.
In this study, the histological definition of endometrial cancer precursor (ECP) lesions is discussed and a comparison is made of clinical and histological parameters of ECP patients and endometrial cancer (EC) patients. ECP lesions were divided in 3 types: adenomatous hyperplasia, atypical hyperplasia and in situ adenocarcinoma. The following parameters were analyzed: age, menopausal status, gynecological and extragynecological familiar cancer incidence, other cancers in the proband, diabetes, obesity, primary infertility, fertility and previous estrogen therapy. Results give support to the hypothesis of the existence of a common biological pathway between ECP and EC. The high frequency of coexistence of both types of lesions in hysterectomy specimens from EC patients studied by step sections adds a confirmatory supporting argument. Measures for primary and secondary prevention of these lesions are proposed.


Ultrastructure of the salivary glands of non-infected and infected glands in Glossina pallidipes by the salivary glands hypertrophy virus.
Light, scanning electron, and transmission electron microscopy analyses were conducted to examine the morphology and ultrastructure of the salivary glands of Glossina pallidipes. Three distinct regions, each with a characteristic composition and organization of tissues and cells, were identified: secretory, reabsorptive and proximal. When infected with the salivary gland hypertrophy (SGH) virus, glands showed a severe hypertrophy, accompanied by profound changes in their morphology and ultrastructure. In addition, the muscular fibers surrounding the secretory region of the glands were disrupted. The morphological alterations in the muscular tissue, caused by viral infection, could be an important aspect of the pathology and may shed light on the mode of action of the SGH virus. Results were discussed with regard to the potential effect of viral infection on normal salivation and on the ability of infected tsetse flies to transmit a trypanosome parasite.


Evolutionary Formation and Distribution of Puumala Virus Genome Variants, Russia.
We analyzed Puumala virus (PUUV) sequences collected from bank voles from different regions of Russia. Phylogenetic analysis revealed PUUV reassortments in areas with the highest hemorrhagic fever with renal syndrome incidence, indicating reassortment might contribute to pathogenic properties of PUUV. Continued surveillance is needed to assess PUUV pathogenicity in Russia.


Temperature dependence of the absolute rate constant for the reaction of ozone with dimethyl sulfide.
Absolute rate constants for the reaction of ozone with dimethyl sulfide (DMS) were measured in a 200-L Teflon chamber over the temperature range of 283-353 K. Measurements were carried out using DMS in large excess over ozone of 10 to 1 or greater. Over the indicated temperature range, the data could be fit to the simple Arrhenius expression as kDMS = (9.96 +/- 3.61) x 10(-11) exp (-(7309.7 +/- 1098.2)/T) cm3/(molecule x s). A compared investigation of the reaction between ozone and ethene had a kC2H4 value of (1.35 +/- 0.11) x 10(-18) cm3/(molecule x s) at room temperature.


Proteoglycans: gene cloning.
Aggrecan is a large proteoglycan that plays roles in numerous tissues during vertebrate development and adult life. The 6,327-nt chick aggrecan coding sequence had been determined from overlapping clones, but a full-length cDNA, needed for use in transgenic expression studies, had not been constructed. The strategy employed to do so was to generate two overlapping cDNA subfragments that shared a unique restriction site in the overlap and then join them at that site. These subfragments were obtained and cloned into the TOPO-TA vector pCR2.1. Digestion of the two constructs with the shared-site enzyme, XbaI, produced vector/5'-cDNA and 3'-cDNA fragments with XbaI-ends; these were ligated to produce the final full-length cDNA.


In-vitro and ex-situ regional mass spectral analysis of phospholipids and glucose in the vitreous humor from diabetic and non-diabetic human donors.
The causes of vitreous humor (VH) liquefaction remain unclear. Diabetes accelerates this process and other ocular diseases. The weakening of the blood-retina barrier observed with diabetes could enhance the rate of transfer of relatively small molecules such as glucose (Glu) and phospholipids (PLs) from the retina to the VH. Glucose and PLs have been detected previously in VH but their regional distributions are not known. The mapping of Glu and PLs in VHs from subjects with and without diabetes could reveal the roles of these molecules in VH liquefaction. Diabetic and non-diabetic human eyes were acquired from the Kentucky Lions Eye Bank and frozen immediately. Each VH was removed and halved along the sagittal plane. One half was stamped on a matrix assisted laser desorption ionization (MALDI) plate. Either p-Nitroanaline (26 mg/mL MeOH:CHCl3) or 2,5-dihydroxybenzoic acid (20 mg/mL H2O:acetonitrile) was used as matrix. Glu and PLs were extracted from the remaining sections and analyzed. Data were acquired using a MALDI-mass spectrometer. The levels of Glu and PLs were significantly greater in VH from diabetics (VHd) compared with VH from non-diabetics (VHnd). VHds showed the highest relative levels of PLs in the posterior VH, followed by the anterior and central regions. Throughout the entire VH, the most abundant PLs were phosphatidylcholines followed by sphingomyelins. For Glu, the relative intensities were ~3 times higher in the posterior region of VHd (12 ± 1.3) compared with VHnd (6.5 ± 0.7) VHs. Regional studies showed that relative to the posterior VHd, the Glu levels were lower in the anterior (8.1 ± 1.0) and central (6.7 ± 0.8) regions. For the VHnds, the values for the central and anterior regions were 5.9 ± 1.2 and 4.7 ± 0.9, respectively. PLs and Glu are most abundant in the posterior region relative to the central and anterior zones of VHs. This trend was observed in VHd and VHnd, but PLs and Glu levels were significantly higher in VHds. These results support the possibility that higher levels of Glu and PLs accelerate VH liquefaction in diabetic patients. As liquefaction begins in the posterior region, the higher abundance of PLs and Glu in this zone also suggests that they may play a role in liquefaction. The specific molecular interactions affected by Glu and PLs in the collagen/hyaluronan/water network need to be examined.


Carascynol A, a hybrid of caryophyllane-type terpenoid and a C6 unit degraded by polyprenylated acylphloroglucinols from Hypericum ascyron.
Carascynol A, an unprecedented 4/9/8 ring system hybrid with a peroxide bridge, was characterized from Hypericum ascyron. The architecture contains a caryophyllane-type moiety and a C6 unit derived from polyprenylated acylphloroglucinols. Its structure and absolute configuration were determined by comprehensive spectroscopic and X-ray diffraction data. Biologically, compound 1 inhibited cell proliferation in LoVo, SW480, and HCT116 cell lines (IC50 = 12.30-24.57 µM).


Plasma proANP1-98 levels are positively associated with central obesity: A cross-sectional study in a general population of China.
Atrial natriuretic peptide (ANP) and its prohormone activating enzyme are associated with central obesity, suggesting there may be a potential relationship between proANP1-98 and central obesity. However, the association is still lack of population-based evidence. We explored the association in a general population of China. We measured plasma proANP1-98, waist circumference and other traditional biomarkers in 2203 participants aged≥30y. Multivariate logistic regression models were used to determine the association between plasma proANP1-98 and central obesity, and odds ratio (OR) and 95% confidence interval (CI) were calculated. High proANP1-98 was significantly associated with increased risk of central obesity in participants, and the multivariate adjusted OR (95% CI) of central obesity associated with the second, third and fourth quartiles of proANP1-98 were 1.33 (1.03-1.72), 1.69 (1.31-2.19) and 1.76 (1.35-2.29), respectively, compared with the lowest quartile of proANP1-98. There was a dose-response relationship between proANP1-98 and risk of central obesity among the participants (Ptrend<0.001). Sensitivity analyses further confirmed these associations. Adding proANP1-98 to a model containing conventional risk factors improved discriminatory power of central obesity (as shown by significant improvement in continuous NRI and IDI). Contrary to known reduced ANP levels in central obesity, we found that plasma proANP1-98 was positively associated with central obesity, suggesting that elevated plasma proANP1-98 may be a marker or a risk factor for central obesity.


Decreased cell-mediated immunity and lack of skeletal problems in broiler chickens consuming diets amended with fusaric acid.
Young female broiler chickens fed diets amended with 0, 35, 75, and 150 mg fusaric acid (FA)/kg diet for 3 weeks showed no aberrations in behavior, feed intake, weight gain, or appearance of the visceral organs. Furthermore, there was no correlation between the dietary concentration of FA and incidence of tibial dyschondroplasia and leg-shape deformities. Ash content of dry fat-free tibiae was not influenced by FA; thus, no rickets was present in these chickens. FA enhanced the humoral response to sheep erythrocytes but significantly reduced cell-mediated cutaneous response to phytohemagglutinin-P.


[Post-traumatic tarsal tunnel syndrome: interest of muscular MRI].
Tarsal tunnel syndrome is a compressive neuropathy of the tibial nerve with multiple causes. This syndrome is difficult to diagnose and can be missed because of its subjective symptomatology. In our patient, suspected post-traumatic tarsal tunnel syndrome was confirmed at MRI. This case highlights muscle signal anomalies caused by their denervation in the tibial nerve territory. MRI can provide supplementary information to the electromyography (EMG) and contribute to positive and etiologic diagnosis of peripheral nerve lesions.


Nasal 'flow' receptors of the rat.
This study was performed to identify trigeminal nasal 'flow' receptors and to investigate their firing characteristics. For this purpose, single unit afferent activity was recorded from the anterior ethmoidal nerve in anesthetized rats breathing through the nose or a tracheostomy. In fourteen rats breathing through the nose, 40 of 73 endings tested were identified as 'flow' receptors for the following characteristics: their spontaneous activity had an inspiratory modulation that disappeared during nasal occlusions, they were markedly stimulated by exposure to cold air and inhibited by warm air. In eleven rats breathing through a tracheostomy, 85 endings were identified as 'flow' receptors being stimulated by a constant nasal airflow (100-300 ml/min) with room air (22-26 degrees C) or cold air (0-15 degrees C), but inhibited with warm air (30-45 degrees C). Fifty-five 'flow' receptors (Type R1 and R2) exhibited a dynamic response to the constant airflow, while the other 30 receptors (Type S) showed a static response. A large proportion of 'flow' receptors (more than 52%) were responsive to tactile stimuli. For all the flow receptors, a decrease in intranasal temperature was the primary factor to excite them. These results suggest that the trigeminal nerve has a number of 'flow' receptors which operate as thermoreceptors.


Antagonistic potential of rhizobacterial isolates against fungal pathogens causing rhizome rot in turmeric.
The study aims to select potent bacterial antagonists to be used as biocontrol agents against rhizome rot disease in turmeric (Curcuma longa L.). A total of 48 bacterial isolates were isolated from the rhizosphere of turmeric. These isolates were screened for their in vitro antagonism against Fusarium solani FS-01 and Pythium aphanidermatum (ITCC 7908). Production of volatile organic compounds and chitinase activity were also performed. Among the tested isolates, two bacterial isolates (IJ2 and IJ10) showed the highest inhibitory activity against these fungal pathogens. GC/MS analysis of the crude extract produced by Pseudomonas sp. IJ2 and B. subtilis IJ10 was found to contain many bioactive compounds with antifungal and antimicrobial activities. The rhizome treatment with these isolates exhibited the lowest percent disease severity with high biocontrol efficacy against the tested pathogens. These isolates with promising antagonistic potential, therefore, can be used as biocontrol agents against rhizome rot in turmeric.


Kallikrein 6 as a serum prognostic marker in patients with aneurysmal subarachnoid hemorrhage.
Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating condition that frequently causes death or significant disabilities. Blood tests to predict possible early complications could be very useful aids for therapy. The aim of this study was to analyze serum levels of kallikrein 6 (KLK6) in individuals with aSAH to determine the relevance of this protease with the outcome of these patients. A reference interval for KLK6 was established by using serum samples (n=136) from an adult population. Additionally, serum samples (n=326) from patients with aSAH (n=13) were collected for 5 to 14 days, to study the concentration of KLK6 in this disease. The correlation between KLK6 and S100B, an existing brain damage biomarker, was analyzed in 8 of 13 patients. The reference interval for KLK6 was established to be 1.04 to 3.93 ng/mL. The mean levels in patients with aSAH within the first 56 hours ranged from 0.27 to 1.44 ng/mL, with lowest levels found in patients with worse outcome. There were significant differences between patients with good recovery or moderate disability (n=8) and patients with severe disability or death (n=5) (mean values of 1.03 ng/mL versus 0.47 ng/mL, respectively) (p<0.01). There was no significant correlation between KLK6 and S100B. Decreased serum concentrations of KLK6 are found in patients with aSAH, with the lowest levels in patients who died.


Esmolol blunts postoperative hemodynamic changes after propofol-remifentanil total intravenous fast-track neuroanesthesia for intracranial surgery.
To investigate whether esmolol is effective in attenuating postoperative hemodynamic changes related to sympathetic overdrive. Clinical study. Operating room of a university hospital. 60 ASA physical status I, II, and III patients, age 18 to 65 years, scheduled for elective craniotomy for supratentorial neurosurgery. Patients were given total intravenous anesthesia (TIVA) during emergence from anesthesia and up to 60 minutes after extubation. Those patients who had hypertension (defined as an increase in systolic blood pressure >20% from baseline values) and tachycardia (defined as an increase >20% in heart rate from baseline) received a loading dose of 500 microg/kg esmolol in one minute, followed by an infusion titrated stepwise (50, 100, 200, and 300 microg/kg per min) every two minutes. The mean dose and duration of esmolol therapy were measured. Of 60 patients, 49 (82%) who received propofol-remifentanil TIVA developed significant tachycardia and hypertension soon after extubation. Treatment with esmolol (500 microg/kg in bolus maintained at a mean rate of 200 +/- 50 microg/kg per min) effectively controlled hypertension and tachycardia in 45 of 49 patients (92%; P < 0.05) within a mean 4.30 +/- 2.20 minutes. After extubation, mean esmolol infusion time was 29 +/- 8 minutes. In patients undergoing elective neurosurgery with propofol-remifentanil TIVA, a relatively small esmolol dose and short infusion time effectively blunts early postoperative arterial hypertension and tachycardia.


The effect of a single colony of the red wood ant, Formica polyctena, on the spider fauna (Araneae) of a beech forest floor.
The predation on spiders in a forest ecosystem by a colony of red wood ants, Formica polyctena, was estimated using a barrier to isolate the colony. Of the ants' total prey, 4.6% were spiders. In order to estimate the effect of F. polyctena within their hunting area on the spider population, the spiders' population density was studied inside and outside the hunting area. Samples of the forest floor were taken, spider webs were counted and pitfall traps were used. No significant difference was found in density or composition of the spider fauna inside and outside the hunting area.


Natural Tooth Color Estimation Based on Age and Gender.
Assessment of the predictability of tooth color coordinates according to the CIELab system to estimate the color of the maxillary central incisor based on patient age and gender. The tooth color of one of the maxillary central incisors of 1361 Caucasian Spanish individuals aged 16 to 89 years, male and female, was measured using the Easyshade compact spectrophotometer. Color coordinates L*, C*, h*, a*, and b* were recorded according to age and gender. The results obtained show that differences in age account for 45% of the total variation of the L (lightness) coordinate; 21% of the variation in coordinate a*, and 17% of the variation in coordinate b* is due to the same reason. At a confidence level of 95% it may be proposed that the mean estimated color difference (ΔEab *) between real natural color and that predicted by the linear regression model is between 6.4 and 6.9 units. In this sample of Caucasians from Spain, teeth became darker yellow and more reddish with increasing age. The L* coordinate is most strongly related to tooth color in aging.


Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice.
Chlorogenic acid is a major polyphenolic component of many plants and beverages, and is particularly abundant in coffee. We evaluated the neuroprotective effects of chlorogenic acid on learning and memory impairment induced by scopolamine (0.5 mg/kg, i.p.), a muscarinic antagonist, using the Y-maze, passive avoidance, and Morris water maze tests. The chlorogenic acid significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze test, and significantly reversed cognitive impairments in mice as measured by the passive avoidance test. In addition, chlorogenic acid decreased escape latencies in the Morris water maze test. In a probe trial session, chlorogenic acid increased the latency time in the target quadrant in a dose-dependent manner. Ex vivo, chlorogenic acid inhibited acetylcholinesterase activity in the hippocampus and frontal cortex. Chlorogenic acid also decreased malondialdehyde levels in the hippocampus and frontal cortex. In vitro, chlorogenic acid was found to inhibit acetylcholinesterase activity (IC₅₀=98.17 μg/ml) and free radical scavenging activity (IC₅₀=3.09 μg/ml) in a dose-dependent manner. These results indicate that chlorogenic acid may exert anti-amnesic activity via inhibition of acetylcholinesterase and malondialdehyde in the hippocampus and frontal cortex.


Sex-based differences and relationship with the restricted knee flexion angle due to aging: a comparative study.
The relationship between inferior patellar mobility (IPM) and knee flexion angle has yet to be elucidated. This study aimed to develop quantitative IPM measurement methods and clarify the relationship between IPM and knee flexion angle in community-dwelling older females. This was a cross-sectional study. Overall, 128 healthy older women (age 65-79 years) were recruited from the community to evaluate the relationship between IPM and knee flexion angle. This study was performed between May 2015 and December 2017. The reference value of and sex differences in IPM were evaluated in 205 healthy young adults aged between 19 and 21 years. IPM was compared between healthy older and young women and was objectively measured using our specially designed patellofemoral arthrometer (PFA). Patellar mobility was calculated by normalization to body height. IPM reliability was assessed before all measurements. Intraclass correlation coefficients for intratester and intertester reliabilities varied from 0.87 to 0.99. The normal range based on two standard deviations of inferior patellar displacement/body height was 5.9-13.5% (young men), 5.1-14.3% (young women), and 1.2-8.8% (older women). IPM was significantly lower in older than young women (P < 0.001). There was a significant positive correlation (r = 0.72 and P < 0.01) between IPM and knee flexion angle in healthy older women unable to flex the knee joint fully. Our PFA has good intratester and intertester reliability. The results suggest that IPM decreases with aging in women. IPM and knee flexion angle are correlated among older women unable to flex the knee joint fully. Not applicable.


Psychiatric comorbidity and gender differences among suicide attempters in Bangalore, India.
Suicides are an entirely preventable cause of death, with current suicide rates being 11.4 per 100,000 population in India. The city of Bangalore in India is often called the suicide capital of India because of its high suicide and attempted suicide rate. This study attempted to evaluate the psychiatric comorbidity and gender differences among suicide attempters presenting to a general hospital in the city of Bangalore, India. Using a structured questionnaire [Structured Clinical Interview for DSM-IV (SCID)-I and SCID-II], the study gathered data on the psychiatric diagnoses as well as the reasons for and mode of attempted suicides on 100 suicide attempters after taking written informed consent. In addition, the Beck Depression Inventory was also used to evaluate the severity of depression, the most commonly detected psychiatric comorbidity. Forty-two percent of the sample had a psychiatric comorbidity, with depression (14%) and dysthymia (12%) being the most common disorders. Among personality disorders (PDs), borderline PD (5%) and dependent PD (3%) were the most commonly detected. Severe depression was detected in 15% of those with a mood disorder. Gender differences were found in both mode and reasons for attempted suicide. The presence of any psychiatric comorbidity was observed to confer a high risk of suicide. All attempters should therefore be comprehensively evaluated by a qualified health care professional, and attempts should be made for continuous follow-up.


Inhibiting effect of levamisole on superoxide production from rat mast cells.
The aim of the present study was to test whether levamisole acts as a superoxide scavenger. The drug was incubated at four different concentrations (range 1, 5, 10, 20 micrograms/ml) with purified rat mast cells which were then induced to generate superoxide ions, by challenge with compound 48/80 (1 microgram/ml). Ten minutes preincubation with the drug completely abolished superoxide ions production. Addition of levamisole to the cell suspension simultaneously with the releaser caused full inhibition of O2(-) generation at the lowest dose, while higher doses failed to suppress 48/80 induced O2(-) generation. In a cell-free superoxide-generating system, like xanthine-xanthine oxidase, levamisole did not act as a superoxide scavenger at any of the doses tested.


Good functional recovery following intervention for delayed suprachoroidal haemorrhage post bleb needling: a case report.
Bleb needling is a recognised procedure in the management of patients with failing trabeculectomies. Suprachoroidal haemorrhage can occur as an unusual complication. We report a pseudophakic man who had early surgical intervention for this complication. This intervention may have contributed to the good recovery of his visual acuity and the minimum changes to his visual fields. A 79-year-old pseudophakic man with chronic open angle glaucoma presented with further deterioration of his right visual field despite maximum medical therapy and a previous trabeculectomy. The right visual acuity was 6/9 with an intraocular pressure (IOP) of 16 mmHg. Bleb needling with 5-fluouracil was performed in a standard manner. His postoperative IOP was 6 mmHg. Thirty-six hours later the visual acuity was reduced to hand movements and two large choroidal detachments where observed clinically, which progressed to suprachoroidal haemorrhages. Five days after the initial needling, the patient had complex surgery involving anterior chamber reformation, a bleb compression suture and drainage of the haemorrhagic suprachoroidal detachments. Subsequently, the patient had a right vitrectomy with endolaser following a vitreous haemorrhage. The final visual acuity was 6/9 with an intraocular pressure of 8 mmHg on travoprost and brinzolamide. The final visual field showed little change when compared with the pre-suprachoroidal haemorrhage visual field. It is important to consider the possibility of delayed suprachoroidal haemorrhage as a complication in bleb needling, and early surgical intervention may be beneficial.


Constrained vertebrate evolution by pleiotropic genes.
Despite morphological diversification of chordates over 550 million years of evolution, their shared basic anatomical pattern (or 'bodyplan') remains conserved by unknown mechanisms. The developmental hourglass model attributes this to phylum-wide conserved, constrained organogenesis stages that pattern the bodyplan (the phylotype hypothesis); however, there has been no quantitative testing of this idea with a phylum-wide comparison of species. Here, based on data from early-to-late embryonic transcriptomes collected from eight chordates, we suggest that the phylotype hypothesis would be better applied to vertebrates than chordates. Furthermore, we found that vertebrates' conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality for normal development. Thus, we propose that the intensively recruited genetic system during vertebrates' organogenesis period imposed constraints on its diversification through pleiotropic constraints, which ultimately led to the common anatomical pattern observed in vertebrates.