Quantification of folpet and phthalimide in food by gas chromatography and mass spectrometry: Overcoming potential analytical artefacts.
Accurate quantification of folpet is problematic because it degrades into phthalimide during sample preparation and analysis by gas chromatography (GC). Thus, EU regulation was recently modified to include phthalimide in the folpet residue definition. However, recent studies have shown that phthalimide could also be generated from different sources, which could lead to an overestimation of the phthalimide content and therefore to false positives. GC coupled with either negative chemical ionisation and single quadrupole mass spectrometry, or electron ionisation with triple quadrupole mass spectrometry (GC-EI-MS/MS), were evaluated for the determination of folpet and phthalimide in food. Both methods were validated in 4 different matrices namely apple puree, rice flour, raspberry puree and infant formula. Better selectivity and precision were obtained with GC-EI-MS/MS. Negligible amounts of phthalimide was found in blank matrices, and validation results met the SANTE/11813/2017 criteria in all matrices at the LOQ concentration levels by using GC-EI-MS/MS.


Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.
This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, β, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.


Dentistry in the USA: a lesson in survival.
A changing and improving environment for the practice of dentistry is occurring in the USA. The details of the events and the lessons to be learned are provided.


Immune reactions of platelets and their clinical significance.
It is recognized that blood platelets with a peculiar cell membrane which carries numerous genetically determined immunogens, but is also intricately associated with the hemostatic process not only participate in immune reactions as a passive target cell, but also as an active functional cell. Pertinent results of animal experiments and of in vivo and in vitro investigations with human blood platelets are reviewed in the attempt to elucidate the role of immune reactions of platelets in the pathogenesis of various human bleeding disorders.


Formation of a cyst-like area after a connective tissue graft for root coverage.
Many techniques have been developed to obtain root coverage. There have been few complications reported with these techniques. This case report chronicles the development of a cyst-like area after a connective tissue partial-thickness double pedicle graft was used to obtain root coverage. The root coverage procedure was performed as previously reported. Postoperatively, in the surgical area, the patient developed occasional swelling. It was possible to express a white material from the area. A biopsy was taken to determine the cause of the clinical findings. Histological evaluation revealed the development of a cyst-like area. The development of cysts does not seem to be a common event. However, this case report demonstrates that they are a possible complication of root coverage procedures.


Acute febrile neutrophilic dermatosis in childhood (Sweet's syndrome).
We report a case of Sweet's syndrome in childhood. Our patients suffered from repeated fevers, chest infections and had characteristic erythematous plaques. The severity of his illness increased with age and warranted oral steroid treatment. We review 16 cases reported to date in the literature and comment on the management and prognosis of the disease in childhood.


Recovery and differentiation of long ripened cheese microflora through a new cheese-based cultural medium.
A partial picture of the typical microflora of PDO Parmigiano Reggiano cheese was achieved by studying the cultivability of lactic acid bacteria associated with its manufacturing and ripening. A comprehensive sampling design allowed for the analysis of the cheese microflora during its production over 20 months of ripening. An innovative cheese agar medium (CAM) was prepared after testing 18 formulations all based on grated Parmigiano Reggiano ripened cheese. During cheese manufacturing and ripening, different samples were sampled and their microflora was recovered using CAM in comparison with other traditional media. Colonies which formed units from the different agar media tested were picked and isolated; the phylogenetic positions of 154 isolated strains were studied at level of species by 16S-rRNA gene sequencing. CAM seems to be able to recover the minority population coming from milk and whey starter, hardly estimable, during the first hours of production, on traditional media.


Nitric oxide monooxygenation (NOM) reaction of cobalt-nitrosyl {Co(NO)}8 to CoII-nitrito {CoII(NO2 -)}: base induced hydrogen gas (H2) evolution.
Here, we report the nitric oxide monooxygenation (NOM) reactions of a CoIII-nitrosyl complex (1, {Co-NO}8) in the presence of mono-oxygen reactive species, i.e., a base (OH-, tetrabutylammonium hydroxide (TBAOH) or NaOH/15-crown-5), an oxide (O2- or Na2O/15-crown-5) and water (H2O). The reaction of 1 with OH- produces a CoII-nitrito complex {3, (CoII-NO2 -)} and hydrogen gas (H2), via the formation of a putative N-bound Co-nitrous acid intermediate (2, {Co-NOOH}+). The homolytic cleavage of the O-H bond of proposed [Co-NOOH]+ releases H2 via a presumed CoIII-H intermediate. In another reaction, 1 generates CoII-NO2 - when reacted with O2- via an expected CoI-nitro (4) intermediate. However, complex 1 is found to be unreactive towards H2O. Mechanistic investigations using 15N-labeled-15NO and 2H-labeled-NaO2H (NaOD) evidently revealed that the N-atom in CoII-NO2 - and the H-atom in H2 gas are derived from the nitrosyl ligand and OH- moiety, respectively.


Non-specific and ski-specific performance development in peri-pubertal cross-country skiers.
To evaluate non-specific and ski-specific performance development in male (M) and female (F) peri-pubertal cross-country skiers and to evaluate their relationship with cross-country skiing (XCS) performance and biological maturation within each age category and sex. Twenty-one and 19 athletes under 14 and 16 years old, respectively (U14 and U16), were tested for biological maturation; non-specific speed, agility, strength, endurance, and balance; ski-specific speed, agility, and endurance. XCS index was considered as average percentage time-gap from the winner in four official races. Sex and age-category effects were verified and a model predicting XCS index was extrapolated for each group. Performance capacities raised across age categories (p < 0.05) except for non-specific speed, agility, balance, and relative arm strength (p > 0.05). F showed advanced biological maturation and greater balance than M (p < 0.05), while M showed higher performance capacities (p < 0.05). XCS index was not related to biological maturation within each group (p > 0.05); its variance was explained by non-specific speed and ski-specific upper-body endurance in M-U14 (p = 0.014), lower-limb strength and ski-specific agility in M-U16 and F-U14 (both p = 0.001), ski-specific upper-body endurance in F-U16 (p = 0.002). Ski-specific performance capacities still develop during peri-puberty, with peri-pubertal M overperforming with respect to F of comparable performance level. XCS index was not influenced by biological maturation withing each age category, but it was rather explained by specific parameters that commonly undergo the "adolescent spurts", accordingly to the average biological maturation level of M and F athletes of each age category.


Action of di-n-propylacetate on the spontaneous and acquired behaviour in goldfish, mice and rats.
The action of n-dipropylacetate (nDPA) is related to the dose. In low doses, nDPA improved the number of conditioned responses with negative reinforcement. In higher doses, the drug inhibited spontaneous and conditioned behaviour. An nDPA produces an increase in gamma-aminobutyric acid (GABA) brain level, results are discussed in relation to the inhibitory action of GABA in the central nervous system.


Cyclo(RGD) peptide-decorated silver nanoparticles with anti-platelet potential for active platelet-rich thrombus targeting.
The development of integrated nanomedicine for prevention and early diagnosis of thrombosis is highly significant. Platelet plays a vital role in thrombotic disorders, offering an ideal target for thromboprophylaxis and imaging of thrombi. We herein fabricated cyclo(RGD) peptide-decorated AgNPs (designated cRGD-AgNPs) for active targeting platelet-rich thrombi. In vitro cytotoxicity and hemolysis assays demonstrated that cRGD-AgNPs have acceptable biocompatibility pattern. Both PEG-AgNPs (non-targeted version) and cRGD-AgNPs can inhibit agonist-mediated platelet aggregation, whereas the latter exhibited significant attenuation on platelet activation and adhesion onto collagen and fibrinogen matrix. Furthermore, the superior binding ability of cRGD-AgNPs with platelet-rich thrombus was demonstrated in static/dynamic condition in vitro. In vivo studies revealed that cRGD-AgNPs could actively target thrombi in a mouse model of carotid artery thrombi with favorable safety. Our results here suggest that cRGD-AgNPs with intrinsic anti-platelet potential might be promising nano theranostics for thromboprophylaxis and active thrombus targeting.


Purification and analysis of a polydnavirus gene product expressed using a poly-histidine baculovirus vector.
The VHv1.1 polydnavirus gene has been implicated in suppressing the encapsulation response in parasitized insects [Li and Webb (1994) J. Virol. 68, 7482-7489]. In order to characterize this gene product and to further our analysis of its immunosuppressive function, we expressed the VHv1.1 using a custom-designed C-terminal poly-histidine baculovirus vector which allows for high expression and single-step purification of the protein. The 34 kDa VHv1.1 protein was expressed in baculovirus-infected cell cultures and in H. virescens larvae. Highly enriched preparations of the secreted VHv1.1 protein were obtained after affinity chromatography using a NTA-(Ni2+) resin. Characterization with purified preparations of the VHv1.1 protein established that the protein is N-glycosylated, containing glycogroups which are PNGase F-sensitive but Endo H-resistant. The recombinant VHv1.1 protein bound to hemocytes in vitro and in vivo and was endocytosed in a manner similar to the native protein produced in CsPDV-infected larvae.


Giant Myxoid Spindle Cell Neoplasm Presenting with Abdominal Swelling and Concurrent Weight Loss.
Retroperitoneal sarcomas may grow extremely large before becoming clinically symptomatic, and curative resection often has high associated morbidity. An 83-year-old man presented with insidious-onset abdominal pain and weight loss owing to a 16.3 × 13.1 × 25.8-cm retroperitoneal high-grade myxoid spindle cell sarcoma. The patient was ultimately deemed to be unfit for surgery before rapidly succumbing to his disease. This case illustrates both the indolent growth seen in these lesions and the importance of proper patient selection. Older patients with large, high-grade lesions and multiple associated comorbidities are often poor surgical candidates, as the associated surgical morbidity outweighs the potential survival benefit. While the ultimate treatment plan relies on shared decision making by the patient and the healthcare provider, the decision to pursue surgical intervention should take into consideration the patient's broader clinical condition.


A critical review in electrocoagulation technology applied for oil removal in industrial wastewater.
EC process, which stands for Electrocoagulation, is considered a widespread wastewater remediation method that is investigated widely for an extensive variety of wastewater resources, based on its flexibility, easy setup, eco-friendly nature, and low footprint. The critical operative factors in the EC process and the crucial relation between EC and the typical chemical coagulation approach had been thoroughly evaluated because they are the main variables that govern the process of contaminant elimination. As a result, the EC process requires further investigations for scale-up simulations in the manufacturing scopes and optimization of operational parameters. Furthermore, the current paper studies the novel integrated separation methods with the combined EC process and also their limitations for improved wastewater remediation process for cleaner wastes, recycling processes, and water recovery. In this paper, the EC enhancement processes toward oil removal from wastewater have been reviewed which includes a concise representation of the source and features of oily wastewater. Additionally, the advanced remediation methods for oil-contained wastewater and the electrocoagulation process are presented. This review summarized the present utilization of electrocoagulation to eliminate oil from wastewater. Besides the process optimization and modeling investigations, the parameters that significantly affect the electrocoagulation remediation effectiveness are evaluated. Finally, the cutting-edge and sophisticated methods of electrocoagulation process for oil removal are presented.


Influence of hormones and growth factors on viability, DNA, and protein content of adult hepatocytes in primary culture.
The survival of adult rat hepatocytes in monolayer culture was studied in the presence of different hormones (neurotensin, oxytocin, thyrotropin releasing hormone, luteinizing hormone releasing hormone, cholecalciferol, bradykinin, substance P, aldosterone, melanocyte stimulating hormone, 3,3',5-triiodo-1-thyronine, corticosterone, human growth hormone, glucagon, insulin, progesterone, testosterone, estradiol, and dexamethasone phosphate) or growth factors (fetal bovine serum). For this purpose trypan blue exclusion, lactate dehydrogenase, and DNA and protein content were measured at 24 and 72 h of culture. 10(-7) M Dexamethasone, a mixture of eight hormones, 10% fetal bovine serum, and a combination of the latter two supplements caused a more than 64% higher DNA content at 72 h when compared to control cultures. A striking agreement of these results with changes of lactate dehydrogenase leakage was observed, whereas trypan blue exclusion gave erratic results. Considerable changes of cell arrangement apparently specific for each supplement were observed by low magnification microscopy. It is concluded that glucocorticoids and fetal bovine serum have an outstanding effect on cell viability and that DNA or protein content or both are reliable indicators of cell viability in amitotic cultures.


Hafnium-an optical hydrogen sensor spanning six orders in pressure.
Hydrogen detection is essential for its implementation as an energy vector. So far, palladium is considered to be the most effective hydrogen sensing material. Here we show that palladium-capped hafnium thin films show a highly reproducible change in optical transmission in response to a hydrogen exposure ranging over six orders of magnitude in pressure. The optical signal is hysteresis-free within this range, which includes a transition between two structural phases. A temperature change results in a uniform shift of the optical signal. This, to our knowledge unique, feature facilitates the sensor calibration and suggests a constant hydrogenation enthalpy. In addition, it suggests an anomalously steep increase of the entropy with the hydrogen/metal ratio that cannot be explained on the basis of a classical solid solution model. The optical behaviour as a function of its hydrogen content makes hafnium well-suited for use as a hydrogen detection material.


[Programmed multichannel bioelectrical management in the treatment of children with secondary osteoarthrosis deformans of the temporomandibular joint under computed tomographic control].
Programmed multichannel bioelectrical regulation was used in the treatment of 19 children aged 5 to 14 with osteoarthrosis deformans of the temporomandibular joint. The treatment resulted in amelioration of the joint function in all the patients: opening of the mouth increased by an average of 7.5 mm, the volume and density of the lateral and medial pterygoid muscles increased, and the density of osseous tissue of the joint process decreased.


The chlorotic symptom induced by Sunflower chlorotic mottle virus is associated with changes in redox-related gene expression and metabolites.
Systemic infections are commonly associated with changes in host metabolism and gene expression. Sunflower chlorotic mottle virus (SuCMoV) causes systemic infection with sugar increase, photoinhibition and increase in antioxidant enzyme activities before chlorotic symptom appearance in sunflower leaves. The aim of this study was to determine if chlorotic symptom development induced by SuCMoV infection is accompanied by changes in different redox-related metabolites and transcripts. Symptom development was analyzed in the second pair of leaves (systemic infection) at different post-inoculation times: before symptom appearance (BS, 4 dpi), and at an early (ES, 7 dpi) and later stage (LS, 12 dpi) of symptom expression. The results showed that the virus reaches the second pair of leaves at 4 dpi. A positive correlation between chlorotic symptom and number of viral copies was also observed. Changes in hydrogen peroxide, glutathione, pyridine nucleotides and ATP content were observed since symptom appearance (ES, 7 dpi). The expression of some of the genes analyzed was also strongly affected by SuCMoV infection. Specifically, down-regulation of both chloroplast-encoded genes and chloroplast-targeted genes: psbA, rbcS, Cu/Zn sod, Fe sod, phosphoglycolate phosphatase, psbO, psaH and fnr was present, whereas the expression of cytoplasmic-targeted genes, apx1, and Cu/Zn sod was up-regulated. Mitochondrial Mn sod decreased at BS stage and aox decreased only at ES stage. Peroxisomal catalase (cat-2) was lower at BS and LS stages. All these results suggest that SuCMoV infection induces progressive changes in determinants of redox homeostasis associated with chlorotic symptom development.


Correlated noise in brain magnetic resonance elastography.
Magnetic resonance elastography (MRE) uses phase-contrast MRI to generate mechanical property maps of the in vivo brain through imaging of tissue deformation from induced mechanical vibration. The mechanical property estimation process in MRE can be susceptible to noise from physiological and mechanical sources encoded in the phase, which is expected to be highly correlated. This correlated noise has yet to be characterized in brain MRE, and its effects on mechanical property estimates computed using inversion algorithms are undetermined. To characterize the effects of signal noise in MRE, we conducted 3 experiments quantifying (1) physiomechanical sources of signal noise, (2) physiological noise because of cardiac-induced movement, and (3) impact of correlated noise on mechanical property estimates. We use a correlation length metric to estimate the extent that correlated signal persists in MRE images and demonstrate the effect of correlated noise on property estimates through simulations. We found that both physiological noise and vibration noise were greater than image noise and were spatially correlated across all subjects. Added physiological and vibration noise to simulated data resulted in property maps with higher error than equivalent levels of Gaussian noise. Our work provides the foundation to understand contributors to brain MRE data quality and provides recommendations for future work to correct for signal noise in MRE.


Sesquiterpene lactones with unusual structure. Their biogenesis and biological activity.
The given review provides data on the new sesquiterpene lactones with unusual structure isolated from various natural sources, e.g. fungi, plants, marine growth; about their spread, biological activity, and the presumed biogenetic pathway of their formation. An attempt was made to biologically justify a wide structural formation variety of new sesquiterpene lactones with the unique structure.


Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor.
A series of 31 resveratrol derivatives was designed, synthesized and evaluated for activation and inhibition of the TRPA1 channel. Most acted as activators and desensitizers of TRPA1 channels like resveratrol or allyl isothiocyanate (AITC). Compound 4z (HUHS029) exhibited higher inhibitory activity than resveratrol with an IC50 value of 16.1μM. The activity of 4z on TRPA1 was confirmed in TRPA1-expressing HEK293 cells, as well as in rat dorsal root ganglia neurons by a whole cell patch clamp recording. Furthermore, pretreatment with 4z exhibited an analgesic effect on AITC-evoked TRPA1-related pain behavior in vivo.


Disease-modifying therapy in MS: a critical review of the literature. Part I: Analysis of clinical trial errors.
Several types of errors are commonly made during the conduct, analysis, and interpretation of clinical trials in multiple sclerosis (MS). These include statistical errors of overestimating the significance of trial results, particularly when multiple endpoints are evaluated. They also include errors arising from the use of inappropriate covariate analyses, meta-analyses, and post hoc subgroup analyses. Interpretation of trial results can also be confounded by regression to the mean, by post hoc data re-analysis, and by the use of a non-concurrent control population. As these kinds of errors continue to plague the medical literature, it has become important for physicians to be able to assess critically the reports of clinical trial results. In turn, this has made it necessary for physicians to become familiar with the rudiments of the fields of statistics, epidemiology, and trial design. It is the purpose of this manuscript, therefore, to provide an overview of these principles through a detailed analysis of these kinds of clinical trial errors, together with examples that have actually occurred in the recently published MS literature.


Reinstatement of cocaine seeking by hypocretin (orexin) in the ventral tegmental area: independence from the local corticotropin-releasing factor network.
Hypocretin (Hcrt), an arousal- and feeding-associated peptide, is expressed in lateral hypothalamic neurons that project to the ventral tegmental area (VTA). Intra-VTA Hcrt reinstates morphine-conditioned place preferences, and intracerebroventricular and intra-VTA corticotropin-releasing factor (CRF) reinstate cocaine seeking. Each is presumed to act, at least in part, through actions local to the VTA. Here, we examined the possibility that VTA perfusion of Hcrt reinstates cocaine seeking and, if so, whether it does so through the VTA mechanism that is implicated in reinstatement by CRF. Rats were trained to lever-press for intravenous cocaine (2 weeks) and then underwent extinction training (saline substituted for cocaine: 3 weeks). Reinstatement behavior was tested and VTA dialysates were collected and assayed for glutamate or dopamine following footshock or perfusion of Hcrt or CRF, with or without Hcrt or CRF antagonists, into the VTA. Ventral tegmental area perfusion of Hcrt-1 or footshock stress reinstated cocaine seeking and caused release of VTA glutamate and dopamine. The effects of Hcrt-1 were blocked by a selective Hcrt-1 antagonist, but not a CRF antagonist, and were not mimicked by Hcrt-2. The Hcrt-1 antagonist did not block CRF-dependent footshock-induced reinstatement or glutamate or dopamine release. The behavioral and neurochemical effects of Hcrt-1 were attenuated but not blocked by kynurenic acid, an ionotropic glutamate antagonist that blocks footshock-induced reinstatement and glutamate release. While Hcrt and CRF are known to interact in some area of the brain, in the VTA proper they appear to have largely independent actions on the mesolimbic dopamine mechanisms of cocaine seeking.


Retrograde axonal transport of cadmium in the rat hypoglossal nerve.
A small volume of radioactively labelled cadmium was injected into the tongue of rats. Two weeks later, the rats were killed and the lower brainstem with the hypoglossal nuclei was dissected out and sectioned in a cryostat. Autoradiography of freeze-dried sections showed accumulation of cadmium in both hypoglossal nuclei. When unilateral nerve section was performed prior to the injection, only the contralateral nucleus was labelled. The results are interpreted as strong evidence for retrograde axonal transport of cadmium in the hypoglossal nerve.


Implementing interactive technology to teach electrocardiographic interpretation online.
Nurses need to accurately interpret electrocardiography (ECG) in order to intervene appropriately and quickly. Unfortunately, nurses struggle with ECG interpretation. One reason for poor ECG interpretation is the lack of kinesthetic pedagogy on properly measuring ECG intervals and durations. Proper measurement of ECG intervals and durations can help nurses accurately interpret the ECG. This manuscript describes the use of interactive technology to develop the skills for measuring ECG intervals and durations for ECG interpretation in an online ECG course. Using constructivist theory, faculty implemented interactive technology (e.g. tablet and E-Pencil) to enable students to measure ECG intervals and durations. Students utilized a checklist to systematically analyze the ECG. The accuracy of ECG interpretation, student satisfaction, and student confidence were assessed at mid-term and final assessments. Accuracy of ECG interpretation increased among students who engaged with the interactive technology. Students reported satisfaction or high satisfaction with the overall course as well as with the interactive technology. Many students faced technical challenges which is an area of improvement. Despite technical challenges, integration of interactive technology into an online ECG course resulted in greater accuracy of ECG interpretation, high satisfaction, and improved confidence.


TRAPP structures reveal the big picture.
Two papers in this issue provide new structural insights into the "TRAnsport Protein Particle" (TRAPP) complexes, which play crucial roles in Golgi function. Both papers focus on TRAPPIII, which activates the Rab protein Ypt1 in yeast or the homologous Rab1 in metazoans. The structures illuminate how TRAPPIII specifically recognizes its Rab protein substrate. Joiner et al (2021) also describe a membrane-anchoring mechanism for yeast TRAPPIII, while Galindo et al (2021) characterize the large subunits that define metazoan TRAPPIII.


Development of a neonatal adverse event severity scale through a Delphi consensus approach.
Assessment of the seriousness, expectedness and causality are necessary for any adverse event (AE) in a clinical trial. In addition, assessing AE severity helps determine the importance of the AE in the clinical setting. Standardisation of AE severity criteria could make safety information more reliable and comparable across trials. Although standardised AE severity scales have been developed in other research fields, they are not suitable for use in neonates. The development of an AE severity scale to facilitate the conduct and interpretation of neonatal clinical trials is therefore urgently needed. A stepwise consensus process was undertaken within the International Neonatal Consortium (INC) with input from all relevant stakeholders. The consensus process included several rounds of surveys (based on a Delphi approach), face-to-face meetings and a pilot validation. Neonatal AE severity was classified by five grades (mild, moderate, severe, life threatening or death). AE severity in neonates was defined by the effect of the AE on age appropriate behaviour, basal physiological functions and care changes in response to the AE. Pilot validation of the generic criteria revealed κ=0.23 and guided further refinement. This generic scale was applied to 35 typical and common neonatal AEs resulting in the INC neonatal AE severity scale (NAESS) V.1.0, which is now publicly available. The INC NAESS is an ongoing effort that will be continuously updated. Future perspectives include further validation and the development of a training module for users.


Neuropathological findings of PSP in the elderly without clinical PSP: possible incidental PSP?
We aimed to describe cases with incidental neuropathological findings of progressive supranuclear palsy (PSP) from the Banner Sun Health Research Institute Brain and Body Donation Program. We performed a retrospective review of 277 subjects with longitudinal motor and neuropsychological assessments who came to autopsy. The mean Gallyas-positive PSP features grading for subjects with possible incidental neuropathological PSP was compared to those of subjects with clinically manifest disease. There were 5 cases with histopathological findings suggestive of PSP, but no parkinsonism, dementia or movement disorder during life. Cognitive evaluation revealed 4 of the 5 cases to be cognitively normal; one case had amnestic mild cognitive impairment (MCI) in her last year of life. The mean age at death of the 5 cases was 88.9 years (range 80-94). All 5 individuals had histopathologic microscopic findings suggestive of PSP. Mean Gallyas-positive PSP features grading was significantly lower in subjects with possible incidental neuropathological PSP than subjects with clinical PSP, particularly in the subthalamic nucleus. We present 5 patients with histopathological findings suggestive of PSP, without clinical PSP, dementia or parkinsonism during life. These incidental neuropathological PSP findings may represent the early or pre-symptomatic stage of PSP. The mean Gallyas-positive PSP features grading was significantly lower in possible incidental PSP than in clinical PSP, thus suggesting that a threshold of pathological burden needs to be reached within the typically affected areas in PSP before clinical signs and symptoms appear.


Noninvasive fetal genotyping of human platelet antigen-1a.
We describe a reliable noninvasive fetal human platelet antigen (HPA)-1a genotyping assay on a real-time polymerase chain reaction (PCR) platform using cell-free fetal DNA isolated from maternal blood. Nonspecific amplification of maternal cell-free DNA is overcome by pre-PCR digestion of the cell-free DNA with the Msp1 restriction enzyme. Noninvasive fetal HPA-1a genotyping offers a safe method for alloimmunised pregnant women to determine whether their fetus is at risk of fetal or neonatal alloimmune thrombocytopenia (FNAIT) and whether interventions to prevent intracranial haemorrhage are required. The availability of this test is relevant to the ongoing debate on screening pregnancies for HPA-1a-mediated FNAIT.


Case report: surgical resection of right ventricular cardiac fibroma in an adult patient.
Cardiac fibromas are rare benign cardiac neoplasms, most frequently occurring in the pediatric population; with very rare cases identified in adults. The tumors are comprised of spindled cells with myofibroblastic ultrastructural features embedded in generally collagenous and elastic stroma. The tumors are intramural in the ventricles, most commonly the left ventricle. Clinical symptoms vary by location and size of tumor and some are asymptomatic. Surgical resection is curative, but rare cases require cardiac transplantation. We report an asymptomatic, large, right ventricular fibroma in a 64-year-old woman. The patient underwent open incisional tumor biopsy via lower hemi-sternotomy, followed by complete tumor resection via full sternotomy a week later after confirming the tumor is benign. The tumor was resected using cardiopulmonary bypass, and the defect of right ventricular free wall was repaired using a prosthetic double-patch technique. The postoperative course was uneventful. The patient was discharged to home on day 4 post-complete tumor resection. This report expands the existing literature for better comprehension and detection of cardiac fibroma patients and also highlights the various imaging modalities, surgical management, and histological analysis.


Multiscale spatiotemporal characteristics of landscape patterns, hotspots, and influencing factors for soil erosion.
Soil erosion is an increasingly serious eco-environmental problem, and effective control of soil erosion is an important part of soil resource protection and ecological restoration. In this study, the multi-scale characteristics and influencing factors of soil erosion were analyzed in the Beijing-Tianjin-Hebei (BTH) region from 2000 to 2015. The results showed that the average soil erosion in the study area was 3500 t/(km2·a), in which the severe erosion areas accounted for 10% of the total area. Although the total soil erosion rate decreased by 60% from 2000 to 2015, the rate of current soil erosion was higher than the soil loss tolerance. The severe erosion area had the highest aggregation index, making it the most suitable for centralized treatment. Meanwhile, the fractal dimension index of severe erosion showed a downward trend from 2000 to 2015. This decrease in complexity led to a more optimistic conservation situation. The hotspot areas overlapped with the relatively high erosion zones and were aggregated as three large patches in the northern, southwestern, and southern BTH regions. Soil erosion distribution depends on both anthropogenic activities and natural conditions. The slope factor, which reflects the impact of natural factors on soil erosion, was the most dominant factor on soil erosion from 2000 to 2010. Conversely, the land use factor, which is mainly controlled by humans, became the dominant factor in 2015. The distribution characteristics and influencing factors of soil erosion both had scale effects. As the scale decreased from city to town, the patches of high and severe erosion classes became more regular and aggregated, the hotspot area had the most concentrated and severe soil erosion rate at the town scale, and human impacts became dominant. Conservation targeting hotspot areas measured at the town scale, which was 20% of the total area, could reduce the total soil loss by 38%. For a region with a complex structure, the main influencing factors showed strong spatial dependence.


Posttraining changes in excitability of the commissural path-CA1 pyramidal cell synapse in the hippocampus of mice.
Mice were partially trained on a bar-press operant conditioning task on continuous reinforcement (CRF). The amplitude of population excitatory postsynaptic potentials (EPSPs) evoked by commissural stimulation of the Ca2 field of the dorsal hippocampus was found to significantly increase 1 h after training and then to decrease. This phenomenon was either not observed or much less evident in mice could not learn the task or which had already been trained on this task.


What are the clinical skills levels of newly graduated physicians? Self-assessment study of an intended curriculum identified by a Delphi process.
To compare and contrast the learned and an intended curricula of practical clinical skills across the three Danish medical schools. The three Danish medical schools had comparable discipline-based curricula with 3 years of mainly basic science and 3(1/2) years of mainly clinical education. Danish physicians work as pre-registration house officers (PRHOs) for 1(1/2) years after graduation. An anonymous questionnaire listing 210 practical clinical skills was mailed to 226 newly graduated Danish physicians. They were asked if they could meet the minimum level for each of the skills listed as identified by a previous Delphi study. The response rate was 80%. None of the responders met the minimum of all the 210 skills. Only 8% (14) met the minimum level for at least 90% (189) of the skills. On average the responders met the minimum of 74% (155) of the skills. More than 90% of the responders mastered basic history and examination skills. The responders did not meet 28 medical emergency procedures. We found that the learned curriculum of clinical skills constituted 75% of the intended curriculum. Those responsible for pre- and postgraduate medical education should be aware of the discrepancy between expected and learned curriculum. We discuss the role of experts in the process of defining the core curriculum.


Oxidative stress response after prolonged exposure of domestic rabbit to a lower dosage of extracted microcystins.
Oxidative stress response after prolonged exposure to a low dose of microcystins (MCs) was studied in liver, kidney and brain of domestic rabbits. Rabbits were treated with extracted MCs (mainly MC-LR and MC-RR) at a dose of 2 MC-LReq. μg/kg body weight or saline solution every 24h for 7 or 14 days. During the exposure of MCs, increase of lipid peroxidation (LPO) levels were detected in all the organs studied, while antioxidant enzymes responded differently among different organs. The enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in liver decreased in the MCs treated animals. In brain, there were obvious changes in glutathione peroxidase (GPx) and GR, while only CAT was obviously influenced in kidney. Therefore, daily exposure at a lower dosage of MCs, which mimicked a natural route of MCs, could also induce obvious oxidative stress in diverse organs of domestic rabbits. The oxidative stress induced by MCs in brain was as serious as in liver and kidney, suggesting that brain may also be a target of MCs in mammals. And it seems that animals may have more time to metabolize the toxins or to form an adaptive response to reduce the adverse effects when exposed to the low dose of MCs.


Incidentalomas, SPEW, and VOMIT-radiological dyspepsia?
• Incidental findings are an inevitable part of radiology reporting.• Detection of incidental findings may be beneficial, but may result in unnecessary further investigation, and potential harm to patients.• Incidental findings should be reported in context, with an attempt to offer guidance as to their significance, and the need to investigate further.


Speech outcomes following pharyngeal flap in patients with velocardiofacial syndrome.
Velocardiofacial syndrome is the most common defined disorder associated with palatal insufficiency. The authors' purpose is to evaluate one surgeon's experience with correction of velopharyngeal insufficiency in velocardiofacial syndrome using a tailored pharyngeal flap. The authors reviewed the records of all children with velocardiofacial syndrome and velopharyngeal insufficiency who were managed with a pharyngeal flap between 1983 and 2009. Data collected included age at operation, preoperative videofluoroscopic findings, speech outcomes, complications, and need for a secondary operation. The authors identified 33 patients with velocardiofacial syndrome and velopharyngeal insufficiency who had postoperative speech evaluations. Velopharyngeal insufficiency was diagnosed at a median age of 5 years. Palatal findings were: Veau type I (n = 4), overt submucous (n = 6), or occult submucous (n = 23). Median preoperative lateral pharyngeal wall movement was 22 percent (range, 0 to 90 percent). Successful correction of velopharyngeal insufficiency was achieved in 29 of 33 patients (88 percent). One patient had a medially displaced right internal carotid artery, and evidenced intraoperative bleeding and required a blood transfusion. One patient developed obstructive sleep apnea. A tailored pharyngeal flap is highly effective for correction of velopharyngeal insufficiency in velocardiofacial syndrome with few complications.


Comparative in vitro antimicrobial susceptibility and synergistic activity of antimicrobial combinations against Helicobacter pylori isolates in Taiwan.
Antimicrobial resistance is a major determinant of Helicobacter pylori treatment failures. We conducted a population-based survey to monitor changing antimicrobial susceptibility of H. pylori isolates in Taiwan, with a focus on combinatorial effects of synergism and the influence of acidity. H. pylori isolates from endoscopic specimens taken from patients enrolled at two medical centers were obtained between January 2008 and December 2009. Minimum inhibitory concentrations (MICs) were determined by agar dilution and Etest methods. Agar media of varying pH (pH 7.3, 6.0, or 5.0) were used to assess whether acidity influences the bactericidal effects of the agents tested. Time-kill assays were used to assess for synergism between different drug combinations. A total of 176 non-duplicate H. pylori isolates from endoscopic specimens were tested. The following MIC90 (mg/L) (susceptible) results were obtained at neutral pH 7.3: amoxicillin, 0.25 (100%); tetracycline, 0.5 (100%); metronidazole, 32 (67.6%); clarithromycin, 0.25 (90.3%); ciprofloxacin, 1 (92.0%); gemifloxacin, 0.5 (94.9%); levofloxacin, 1 (93.2%); and moxifloxacin, 1 (91.5%). A decrease in pH from 6.0 to 5.0 significantly decreased the antimicrobial activity of levofloxacin and moxifloxacin against H. pylori. For clarithromycin-susceptible isolates, levofloxacin combined with clarithromycin provided both synergistic and bactericidal effects. For clarithromycin-resistant isolates with amoxicillin hypersusceptibility (MIC <0.01 mg/L), levofloxacin with amoxicillin or minocycline had at best additive effect but no bactericidal effects. Amoxicillin, tetracycline, clarithromycin, and fluoroquinolones, but not metronidazole, showed good in vitro anti-H. pylori activity (>90% susceptible). Synergism was only observed for clarithromycin-susceptible isolates. Acidity adversely influenced the antimicrobial activity of levofloxacin against H. pylori.


Arenibacterium arenosum sp. nov., isolated from sea sand.
A Gram-negative, non-motile, short rod-shaped aerobic bacterial strain CAU 1593T was isolated from a coastal sand sample collected in the Republic of Korea. Cells of strain CAU 1593T grew optimally at 30 °C and pH 7.5 in 4% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain CAU 1593T had the highest similarity to Arenibacterium halophilum (97.5%). The whole genome of strain CAU 1593T was 3,979,826 bp with 26 contigs, and the DNA G + C content was 64.3 mol%. The major fatty acid of strain CAU 1593 T was summed feature 8 (C18:1 ω7c/C18:1 ω6c). Q-10 was the only respiratory quinone. The polar lipids were composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two phosphoglycolipids, an unidentified glycolipid, and an unidentified lipid. Based on the results of chemotaxonomic, phylogenetic, and phenotypic analyses, strain CAU 1593T represents a novel species in the genus Arenibacterium, which is named Arenibacterium arenosum sp. nov. The type strain is CAU 1593T (= KCTC 82402T = MCCC 1K05671T).


Aluminum accumulation in a lotic mayfly at low pH--a laboratory study.
The authors experimentally studied the occurrence of aluminum (Al) accumulation in nymphs of the mayfly Heptagenia sulphurea at low pH (4.5). Nymphs were exposed to two Al concentrations (0.2 and 2 mg inorganic Al liter-1), and two exposure times (2 and 4 weeks), the longer time period also including a molting phase. The major part of the Al was deposited on/in the exuviae of the nymphs, as Al determination in nymphs showed a 70% decrease in Al content after molting. When nymphs were exposed for two instar periods, with a molt in between. Al content almost doubled (2.34 mg Al g-1 dry wt) compared with that of a one-instar treatment (1.24 mg Al g-1 dry wt). This indicated that Al also accumulated within the mayfly nymphs. Determination of Al in emerged adults confirmed that most of the metal was deposited externally on the nymphs. No clear indications of Al accumulation were found in this short-term experiment. The implications for food-web accumulation of Al are that internally accumulated Al may be transferred to terrestrial predators by mayflies and other aquatic insects that leave their final exuvium in the water. However, aquatic insects that make their final molt in the terrestrial environment, and thereby bring adsorbed Al out of the water are more likely vectors.


Determination of aminorex in human urine samples by GC-MS after use of levamisole.
The Drug Enforcement Administration (DEA) reports that as of October 2010, 79% of all cocaine seized in the United States contained levamisole. The equine conversion of levamisole to aminorex has been demonstrated. However, the metabolic fate of levamisole in humans is unknown. Nevertheless, as aminorex is amphetamine-like and hallucinogenic, it may be used as an adulterant to increase the effects of cocaine. We report here the results of in vivo studies demonstrating for the first time that not only equine, but also canine and human metabolism all result in aminorex formation. Levamisole and aminorex were extracted from real urine samples by liquid-liquid extraction and identified and quantified by GC-MS (identification by 3 ions per substance, LLOQ at 0.15ng/ml for both).


The role of nitric oxide in osteoarthritis.
Elevated levels of markers of nitric oxide (NO) production are found in osteoarthritic joints suggesting that NO is involved in the pathogenesis of osteoarthritis (OA). In OA, NO mediates many of the destructive effects of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) in the cartilage, and inhibitors of NO synthesis have demonstrated retardation of clinical and histological signs and symptoms in experimentally induced OA and other forms of arthritis. As an important factor in cartilage, the regulation of inducible nitric oxide synthase (iNOS) expression and activity, and the effects of NO are reviewed, especially in relation to the pathogenesis of OA.


A fast, reliable, and sensitive method for detection and quantification of Listeria monocytogenes and Escherichia coli O157:H7 in ready-to-eat fresh-cut products by MPN-qPCR.
In the present work we developed a MPN quantitative real-time PCR (MPN-qPCR) method for a fast and reliable detection and quantification of Listeria monocytogenes and Escherichia coli O157:H7 in minimally processed vegetables. In order to validate the proposed technique, the results were compared with conventional MPN followed by phenotypic and biochemical assays methods. When L. monocytogenes and E. coli O157:H7 were artificially inoculated in fresh-cut vegetables, a concentration as low as 1 CFU g(-1) could be detected in 48 hours for both pathogens. qPCR alone allowed a limit of detection of 10(1) CFU g(-1) after 2 hours of enrichment for L. monocytogenes and E. coli O157:H7. Since minimally processed ready-to-eat vegetables are characterized by very short shelf life, our method can potentially address the consistent reduction of time for microbial analysis, allowing a better management of quality control. Moreover, the occurrences of both pathogenic bacteria in mixed salad samples and fresh-cut melons were monitored in two production plants from the receipt of the raw materials to the early stages of shelf life. No sample was found to be contaminated by L. monocytogenes. One sample of raw mixed salad was found positive to an H7 enterohemorrhagic serotype.


Immunization of susceptible mice with gp43-pulsed dendritic cells induce an increase of pulmonary Paracoccidioidomycosis.
The development of the appropriate CD4 Th subset is important for disease resolution and several studies have shown that different outcomes of a disease can be obtained by influencing the commitment of precursors to either, Th1 or Th2 lineage. Dendritic cells (DCs) are able to initiate response in naïve T cells and they also participate in Th cell education. In the present study we demonstrated that purified gp43 lead to down-regulation of MHC-II and adhesion properties of immature DCs and in LPS-induced DCs maturation. It was also shown that purified gp43 from Paracoccidioides brasiliensis has the same inhibitory effect on IL-12 release. Mice infected with Paracoccidioides brasiliensis that received DCs plus gp43 plus LPS had a significant increase of the lung colony forming units when compared with control (not immunized) or those that received only DCs plus LPS. Thus, the granuloma morphology seen in immunized mice was different when compared with non-immunized controls. These data suggest that gp43 affects many functions of the host cells, indicating that these alterations might be used by Paracoccidioides brasiliensis to reduce the effectiveness of the immune response thus facilitating the establishment and fate of primary infection in susceptible host.


[P70S6K is involved in the inhibition of testosterone production in TM3 mouse Leydig cells overexpressing Cox7a2].
To investigate the effects of Cox7a2 on the LH-induced testosterone production and the involved autophagy regulating signals in TM3 mouse Leydig cells. The Cox7a2-pEYFP-N1 fluorescent protein vector was constructed and transfected into TM3 mouse Leydig cells. The level of testosterone was determined by ELISA, and the effects of Cox7a2 on the expression of the steroidogenic acute regulatory protein (StAR) and the phosphorylation of the autophagy regulatory factor P70S6K were detected by Western blot. LH stimulation increased the StAR protein expression and testosterone production, while Cox7a2 decreased P70S6K phosphorylation, reduced StAR expression and consequently inhibited LH-induced testosterone biosynthesis in the TM3 Leydig cells. Cox7a2 inhibits testosterone production by decreasing the StAR protein expression, which might be at least in part related with the activation of autophagy in TM3 mouse Leydig cells.


Simultaneous determination of N-acetyl-p-aminophenol and p-aminophenol with poly(3,4-ethylenedioxythiophene) modified glassy carbon electrode.
A sensitive and selective method was developed for the determination of N-acetyl-p-aminophenol (APAP) and p-aminophenol (PAP) using poly(3,4-ethylenedioxythiophene) (PEDOT)-modified glassy carbon electrode (GCE). Cyclic voltammetry and differential pulse voltammetry were used to investigate the electrochemical reaction of APAP and PAP at the modified electrode. Both APAP and PAP showed quasireversible redox reactions with formal potentials of 367 mV and 101 mV (vs. Ag/AgCl), respectively, in phosphate buffer solution of pH 7.0. The significant peak potential difference (266 mV) between APAP and PAP enabled the simultaneous determination both species based on differential pulse voltammetry. The voltammetric responses gave linear ranges of 1.0×10(-6)-1.0×10(-4) mol L(-1) and 4.0×10(-6)-3.2×10(-4) mol L(-1), with detection limits of 4.0×10(-7) mol L(-1) and 1.2×10(-6) mol L(-1) for APAP and PAP, respectively. The method was successfully applied for the determination of APAP and PAP in pharmaceutical formulations and biological samples.


Development of Natural Luminescent Powder for the Detection of Latent Fingerprint.
Background and Objective: Nowadays, Dyes is widely used to improve fingerprints identification test. Natural dyes are another interesting way that can be used instead of chemical dyes because of its non-toxicity and lower cost. In this research, the development of rust powder from Plumeria tree was applied for fingerprints identification due to its fluorescence property under UV. Rust and Small Particle Reagent (SPR), containing ZnCO3 were applied to detect hidden fingerprints on non-porous surfaces in both dried and wet condition. Materials and Methods: Yellowish Rust from Plumeria tree was extracted with ethanol, grinded, dried and then mixed with ZnCO3. Powder slurry was sprayed over fingerprint mark on different surfaces and monitored in both dried and wet condition. Visualization of fingerprint under UV was observed. Scanning microscope (SEM), UV-visible spectroscopy (UV-VIS), Fourier-Transform Infrared Spectroscopy (FTIR) and Energy-Dispersive X-ray (EDX) were also used to characterize physical and chemical properties of rust powder. Results: Fingerprints identification by dust technique using Plumeria rust powder as ingredient, provide best quality enhancement of fingerprints under UV light due to its fluorescent property, whereas a conventional technique of Small Particle Reagent technique (SPR) doesn't show fluorescent under UV. Data from SEM and FTIR show slight adhesion between zinc carbonate particles and rust powder. Conclusion: Fluorescence properties of rust powder is still interesting. Further improvement in powder recipe will be further investigated.


Education in family and community health: the challenge faced by a new medical school.
This paper describes the efforts of the Department of Family and Community Health at Sultan Qaboos University in providing opportunities for the development of 'hands-on' problem-solving skills appropriate for Oman. The curriculum of the Department is discussed, highlighting the unusual emphasis of this discipline in both the preclinical and clinical curriculum of the College of Medicine. The importance of continuous assessment and supervision of students is discussed. Course-work in the preclinical curriculum of the Department is kept to a minimum. Field-work forms an important part of preclinical training, where application and problem-based learning are emphasized. During the clinical years the students are exposed to an integrated series of lectures and practicals covering core knowledge in clinical medicine. Practical clinical training, over a total period of 15 weeks, takes place at a variety of sites where common problems in primary health care in Oman are handled by students under supervision.


[Diverticular disease: stage-related diagnostic imaging].
Diverticular disease frequently leads to emergency admissions. Clinical parameters are not sufficiently accurate to determine the extent of acute colonic diverticulitis, thus a quick, reproducible and valid diagnostic imaging procedure is required. In the following, the imaging methods commonly used for the diagnostic work-up and staging of diverticulitis are presented and classified in the context of the data situation and clinical reality. Multidetector computed tomography (MDCT) is the current diagnostic gold standard for the imaging evaluation of diverticulitis and the basis for guideline-conform treatment decisions according to the classification of diverticular disease (CDD). The role of magnetic resonance imaging (MRI) in the evaluation of diverticulitis will have to be investigated but a more profound integration of this method can already be predicted. Point-of-care ultrasound for initial diagnosis and follow-up assessment will become more important, analogous to FAST in trauma patients.


Snoring and obstructive sleep apnea: compliance with oral appliance therapy.
To assess the effectiveness of oral appliances in clinical practice. Survey of 110 subjects. Hospital-based dental practice. Questionnaire. Compliance and control of sleepiness and snoring. Fifty-seven percent of respondents were compliant with therapy, reporting control of sleepiness and snoring. More than 50% of those on oral appliance therapy reported continued use after at least 18 months.


Nonspecific radiographic abnormalities in collagenous colitis.
Collagenous colitis (CC) is characterized clinically by a chronic, watery diarrhea. Pathologically, there is a chronic lymphocytic infiltrate with abnormal thickening of the subepithelial collagen layer. This disease occurs predominantly in females, and is more frequent in the elderly. Previous clinical studies suggest that radiographic examination of the colon is of no value in this condition. We reviewed five cases of CC all of whom had colon examination within 2 weeks of the biopsy. Two of our patients showed evidence of mucosal granularity and irregularity of the rectosigmoid on double-contrast barium enema (DCBE). One patient had nodularity of the rectal wall on single-contrast colon examination. Two patients had no inflammatory changes evident on colon examination. These radiographic changes are nonspecific and may be seen in other forms of colitis, particularly ulcerative colitis and nonspecific proctitis.


Alum split applications strengthened phosphorus fixation and phosphate sorption in high legacy phosphorus calcareous soil.
High phosphorus (P) saturation arising from historic P inputs to protected vegetable fields (PVFs) drives high P mobilisation to waterbodies. Amendment of soils with alum has shown potential in terms of fixing labile P and protecting water quality. The present 15 month pot experiment investigated P stabilisation across single alum application (Alum-1 treatment, 20 g alum/kg soil incorporated into soil before the maize was sown), alum split applications (Alum-4 treatment, 5 g alum/kg soil incorporated into soil before each crop was sown i.e. 4 × 5 g/kg) and soil only treatment (Control). Results showed that the Alum-1 treatment caused the strongest stabilisation of soil labile P after maize plant removal, whereas the P stabilisation effect was gradually weakened due to the transformation of soil non-labile P to labile P and the reduced active Al3+ in soil solution. For the Alum-4 treatment, soil labile P decreased gradually with each crop planting and was lower than the Alum-1 treatment at the end of the final crop removal, without any impairment on plant growth. The better P stabilisation at the end of Alum-4 treatment was closely correlated with a progressive supply of Al3+ and a gradual decrease of pH, which resulted in higher contents of poorly-crystalline Al, Fe and exchangeable Ca. These aspects were conducive to increasing the soil P stabilisation and phosphate sorption. In terms of management, growers in continuous cropping systems could utilise split alum applications as a strategy to alleviate P losses in high-P enriched calcareous soil.


A systematic analysis of the skeletal muscle miRNA transcriptome of chicken varieties with divergent skeletal muscle growth identifies novel miRNAs and differentially expressed miRNAs.
Functional studies have demonstrated that microRNAs (miRNAs or miRs) play critical roles in a wide spectrum of biological processes including development and disease pathogenesis. To investigate the functional roles that miRNAs play during chicken skeletal muscle development, the miRNA transcriptomes of skeletal muscles from broiler and layer chickens were profiled using Solexa deep sequencing. Some miRNAs have multiple isoforms and several miRNAs* are present at higher levels than their corresponding miRNAs. Thirty three novel and 189 known chicken miRNAs were identified using computational approaches. Subsequent miRNA transcriptome comparisons and real-time PCR validation experiments revealed 17 miRNAs that were differentially expressed between broilers and layers, and a number of targets of these miRNAs have been implicated in myogenesis regulation. Using integrative miRNA target-prediction and network-analysis approaches an interaction network of differentially expressed and muscle-related miRNAs and their putative targets was constructed, and miRNAs that could contribute to the divergent muscle growth of broiler and layer chickens by targeting the ACVR2B gene were identified, which can causes dramatic increases in muscle mass. The present study provides the first transcriptome profiling-based evaluation of miRNA function during skeletal muscle development in chicken. Systematic predictions aided the identification of potential miRNAs and their targets, which could contribute to divergent muscle growth in broiler and layer chickens. Furthermore, these predictions generated information that can be utilized in further research investigating the involvement of interaction networks, containing miRNAs and their targets, in the regulation of muscle development.


Control of enzymatic browning in apple slices by using ascorbic acid under different conditions.
Control of phenol oxidase activity in apple slices by the use of ascorbic acid at different pH values, temperature and time of incubation was investigated. The enzyme was almost inactivated at 1% and 1.5% ascorbic acid. Ascorbic acid solution (1%) caused a remarkable inhibition with the increasing acidity up to pH = 1. Heating treatments for apple slices dipped in 1% ascorbic acid caused a reduction of enzymatic browning, optimum temperature for inactivation of the enzyme was between 60-70 degrees C for 15 minutes. Increasing the time of dipping apple slices in 1% ascorbic acid solutions and at different pH values reduce phenolase activity.


Metagenome analysis of the root endophytic microbial community of Indian rice (O. sativa L.).
This study reports the root endophytic microbial community profile in rice (Oryza sativa L.), the largest food crop of Asia, using 16S rRNA gene amplicon sequencing. Metagenome of OS01 and OS04 consisted of 11,17,900 sequences with 300 Mbp size and average 55.6% G + C content. Data of this study are available at NCBI Bioproject (PRJNA360379). The taxonomic analysis of 843 OTU's showed that the sequences belonged to four major phyla revealing dominance of Proteobacteria, Firmicutes, Cyanobacteria and Actinobacteria. Results reveal the dominance of Bacillus as major endophytic genera in rice roots, probably playing a key role in Nitrogen fixation.


The role of interventional radiology in the management of refractory bile leaks.
Refractory bile leaks represent a damaging sequela of hepatobiliary surgery and direct trauma. Management of bile leaks represents a challenging clinical problem. Despite advances in endoscopic techniques, interventional radiology continues to play a vital role in the diagnosis and management of refractory bile leaks. This article reviews strategies for optimizing the diagnosis and management of bile leaks and provides an overview of management strategies, including the management of complicated biliary leaks.


The rate of blastocysts production following vitrification with step-wise equilibration of immature mouse oocytes.
Cryopreservation and in vitro maturation (IVM) of oocyte is becoming an important technique in infertility treatment and fertility preservation. Also it has been proposed to establish a genetic resource bank for endangered or commercially important animal species. The aim of this study was to evaluate viability, maturation and fertilization rate of mouse immature oocytes after single and stepwise vitrification procedure. Oocytes were obtained from 4 weeks old female mice 48h after intraperitoneal injection of 7.5 IU pregnant mare serum gonadotropin (PMSG). Collected oocytes before vitrification were exposed to cryoprotectant, which was composed of 30% (v/v) ethylene glycol, 18% (w/v) Ficoll-70, and 0.3 M sucrose, either by single step or in a step-wise way. After vitrification and storage in liquid nitrogen, the oocytes were warmed and washed two times in medium TCM199 and then subjected to IVM, fertilization and subsequent development to blastocysts. The oocytes survival rates after vitrifying-warming (88.96%), maturation rate (73.23%), the capacity of fertilization (57.80%) and embryonic development to blastocyst (16.41%) in the step-wise exposure were significantly higher (p<0.001) compared with corresponding rate in the single step procedure. The results suggest that vitrification with step-wise procedure has positive effects on maturation and developmental capacity of mice germinal vesicle oocytes in compare with single step vitrification procedure.


A review of antioxidant and pharmacological properties of phenolic compounds in Acacia confusa.
In the present review article, the phytochemical, antioxidant and pharmacological studies are congregated and summarized concerning the current knowledge of the phenolic compounds of a traditional medical plant Acacia confusa in Taiwan. This plant is native to Taiwan and South-East Asia. It possesses major pharmacological activities, including antioxidant and radical scavenging activity, hepatoprotective effect, xanthine oxidase inhibition, semicarbazide-sensitive amine oxidase inhibition, angiotensin I converting enzyme inhibition, antihyperuricemic effect and anti-inflammatory activity. Phenolic compounds, especially flavonoids, flavonol glycoside and phenolic acid derivatives, are the main phytochemical compounds isolated from different plant parts of A. confusa. Recent interest in this species has focused on pharmacological investigations of the phytochemicals which exhibit potent antioxidant activity based on the multiple phenolic functionalities. The consequence of this review will further extend the potential applications of this plant and offer persuasive support to its future use in the fields of clinical medicine and health functional food.


Convict Code, Risky Lifestyles, and Violent Victimization Among Inmates in South Korea.
The adherence of the convict code and involvement in risky lifestyles lead to increased rates of victimization; however, empirical scrutiny regarding the interaction between the convict code and risky lifestyles remains unexplored. The current study bridges this gap in the victimization literature by examining the interaction effect between the convict code and risky lifestyles on victimization experience incarcerated offenders within South Korean prisons. Results indicate there both the convict code and risky lifestyles are positively and significantly associated with the risk of victimization. When combined, an interaction effect is present, suggesting that the relationship between the convict code and violent victimization is stronger as inmates engage in risky lifestyles more frequently. A discussion of theoretical implications is offered, highlighting the similarities of the convict code with western prison settings.


Inhibition of CYP450 1A and 3A by berberine in crucian carp Carassius auratus gibelio.
Berberine has long been considered as an antibiotic candidate in aquaculture. However, studies regarding its effects on drug-metabolizing enzymes in fish are still limited. In the present study, the effects of berberine on cytochrome P4501A (CYP1A) and CYP3A in crucian carp were investigated. Injection of different concentrations of berberine (0, 5, 25, 50, and 100mg/kg) inhibited the CYP1A mRNA expression, thereby inhibiting further the catalytic activity of CYP1A-related ethoxyresorufin-O-deethylase (EROD). Furthermore, both CYP1A expression and EROD activity were further inhibited with increasing berberine concentrations. In addition, the CYP3A expressions at both the mRNA and the protein levels were downregulated by higher berberine concentrations. The catalytic activity of CYP3A-related erythromycin N-demethylase (ERND) was also inhibited by berberine at a dose of no less than 25mg/kg. Moreover, at the berberine concentration exceeding 25mg/kg, the inhibition of CYP3A expression and ERND activity increased with increasing berberine concentrations. In vitro experiments were also performed. When berberine was pre-incubated with the crucian carp liver microsomes, it competitively inhibited the corresponding EROD activity with the IC(50) of 11.7 μM. However, the ERND activity was slightly inhibited by berberine with the IC(50) of 206.4 μM. These results suggest that, in crucian carp, berberine may be a potent inhibitor to CYP1A, whereas the CYP3A inhibition needs a higher concentration of berberine.


Decline of isometric force and fatigue resistance in skeletal muscles from spontaneously hypertensive rats.
Skeletal muscles from 6- to 7-month-old male spontaneously hypertensive rats showed a decrease in functional capacity compared with muscles from age-matched normotensive Wistar-Kyoto rats. Predominantly slow-twitch, oxidative soleus muscles developed less force (normalized to muscle wet weight) and were less resistant to fatigue. Heterogeneous, but largely fast-twitch, oxidative-glycolytic medial gastrocnemius muscles generated less force, were smaller in size (normalized to body weight), and did not demonstrate the same degree of stimulation-associated potentiation (staircase effect) as did the medial gastrocnemius of the normotensive rats. The reduced endurance of the soleus of hypertensive rats was not associated with either fiber redifferentiation or capillary "rarification," and the majority of the decline in force with time could not be attributed to impaired neuromuscular transmission. The decrease in muscle capacity in the spontaneously hypertensive rat, thus, appears to be the result of adaptive changes localized in the muscle cells themselves. The adaptive changes, regardless of site, have a pronounced negative effect on muscle function, and could significantly influence motor performance and antihypertensive therapy.


Disuse osteoporosis in patients with total hip prostheses.
Aseptic loosening of total hip arthroplasty is still a serious problem. Bone quality might be one of the major factors influencing loosening. In a previous study, bone loss during the reparation phase was evaluated with modified computed tomography at the site of the implant. The present study documents the degree of disuse osteoporosis prior to and after surgery. Bone density of both tibiae of patients with unilateral artificial hip joints was evaluated longitudinally. Preoperatively a significant right-left difference was found, that has to be attributed to the preoperative unloading of the diseased leg. After surgery a slight but significant bone loss was found in both legs attributable to the immobilization following surgery and the reduced activity in the first 6 months. In successfully operated cases this loss is temporary. In one patient bone loss continued; after 1 year there are now clinical signs of implant loosening. Although the spectrum of physical activity in our group was wide, no correlation between activity and bone loss has been found so far.


Pharmacists in general practice--a proposed role in the multidisciplinary team.
Australia continues to explore methods to restructure primary health care services to meet stressors within the health system. The primary health care strategy and its support for larger general practices and multidisciplinary team contributions, raise opportunities for re-engineering general practice services.


Clinical, toxicological, and pharmacological studies of combination chemotherapy of adenocarcinoma with adriamycin and Baker's antifolate.
Ten patients with disseminated adenocarcinoma were treated with combination chemotherapy employing Adriamycin and Baker's Antifolate (BAF). There were seven patients with lung adenocarcinoma, two of whom achieved partial remission while the remaining five had their disease stabilized. Drug toxicity to the bone marrow, gastrointestinal mucosa, and skin was dose-limiting and was greater than the known toxicities of the individual drugs. Pharmacological studies of both drugs were performed on five patients to determine whether abnormal pharmacokinetics could explain this collateral toxicity. Adriamycin plasma concentrations and disappearance seemed to be unaffected by BAF. However, BAF levels were prolonged, apparently due to an Adriamycin effect on the plasma elimination of BAF, resulting in a prolonged exposure of sensitive tissues and organs to BAF. Consequently, when BAF and Adriamycin are used in combination, appropriate dose and schedule changes must be made to avoid any potentially serious side effects.


The first synthesis of chiral PNA monomer-cyclen conjugates.
A synthetic route to novel chiral PNA monomer-cyclen conjugates was described for the first time, the targeted products were obtained in high yields under mild reaction conditions. The preliminary results demonstrated that the uracil-PNA monomer-cyclen conjugates can rapidly bind Zn2+ in aqueous solution, and the structure of the Zn(II) complex was confirmed facilely by HRMS spectra, 1H NMR spectra and elemental analysis.


Severe Clostridium difficile infection with extremely high leucocytosis complicated by a concomitant bloodstream infection caused by Klebsiella pneumoniae after osteomyelitis surgery: A case report.
Clostridium difficile is one of the most common healthcare-associated infections. Pseudomembranous colitis is a serious complication of Clostridium difficile infection (CDI) after septic surgery and antibacterial therapy. A sudden white blood cell (WBC) count increase and extremely high leucocytosis may be a predictor of a poor outcome. A 77 years old male was hospitalised because of lower leg osteomyelitis and was operated. He received antibacterial treatment with Cefazolin for three days and then developed a high WBC count. The course of the disease was fulminant, with a rapid increase in the WBC count up to 132,000/mm3 and a septic shock, and required cardiovascular and ventilatory support. The patient was started on intravenous Metronidazole (500 mg every eight hours) and oral Vancomycin (500 mg every six hours). The patient's condition gradually improved over a period of six days. Then a hyperthermia above 39 degrees Celsius, hypotension and painful abdominal bloating developed, and the WBC count peaked to 186,000/mm3. The blood cultures were positive for Klebsiella pneumoniae. The patient died. In our case, we describe a community-onset, healthcare-facility-associated, severe CDI complicated by a blood stream infection. The administration of oral Vancomycin, which is highly active against the intestinal flora, could have been responsible for the persistence and overgrowth of Klebsiella pneumoniae. Severe CDIs after orthopaedic surgery and antibacterial treatment complicated by the development of nosocomial infection significantly worsen the prognosis of the disease. Careful consideration of antibacterial therapy and early symptom recognition may help prevent catastrophic events.


Intrauterine insemination with or without mild ovarian stimulation in couples with male subfertility due to oligo/astheno- and/or teratozoospermia or antisperm antibodies: a prospective cross-over trial.
Seventy-three couples with male subfertility, which was due to oligo/astheno- and/or teratozoospermia (n = 63) or antisperm antibodies (n = 10), were randomly assigned to sequential timed natural intercourse, intrauterine insemination (IUI) and IUI + mild ovarian hyperstimulation. From the analysis of 384 observed cycles, IUI was shown to be effective in oligo/asthenozoospermia without severe teratozoospermia, when it was associated with moderate multifollicular induction, and in male immunologic subfertility, IUI was highly effective in nonstimulated cycles also.


Antiangiogenic Therapy for Malignant Brain Tumors: Does It Still Matter?
To summarize the mechanisms of tumor angiogenesis and resistance to antiangiogenic therapy, and the influence on tumor microenvironment. Several clinical trials have investigated the activity of anti-VEGF monoclonal antibodies and tyrosine kinase inhibitors in glioblastoma, shedding the light on their limitations in terms of disease control and survival. We have outlined the mechanisms of resistance to antiangiogenic therapy, including vessel co-option, hypoxic signaling in response to vessel destruction, modulation of glioma stem cells, and trafficking of tumor-associated macrophages in tumor microenvironment. Moreover, novel generation of antiangiogenic compounds for glioblastoma, including small interfering RNAs and nanoparticles, as a delivery vehicle, could enhance selectivity and reduce side effects of treatments. There is still a rationale for the use of antiangiogenic therapy, but a better understanding of vascular co-option, vascular mimicry, and dynamic relationships between immunosuppressive microenvironment and blood vessel destruction is crucial to develop next-generation antiangiogenic compounds.


Metabolic reprogramming and metabolic sensors in KSHV-induced cancers and KSHV infection.
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus associated with several human cancers. KSHV infection and KSHV-induced anabolic cell proliferation and cellular transformation depend on reprogramming of cellular metabolic pathways, which provide the building blocks and energy for the growth of both the virus and the infected cells. Furthermore, KSHV dysregulates numerous metabolic sensors including mTOR, AMPK, CASTOR1 and sirtuins to maintain cellular energetic homeostasis during infection and in KSHV-induced cancers. In this review, we summarize the recent advances in the understanding of KSHV hijacking of metabolic pathways and sensors, providing insights into the molecular basis of KSHV infection and KSHV-induced oncogenesis. In addition, we highlight the critical metabolic targets and sensors for developing potential new therapies against KSHV infection and KSHV-induced cancers.


Inferior collicular seizure generalization produces site-selective cortical induction of cyclooxygenase 2 (COX-2).
Given the potential role of mitogen-inducible cyclooxygenase (COX-2) in CNS damage, patterns of COX-2 induction were determined both before and after seizure generalization from the inferior collicular cortex into the forebrain. With midbrain seizures, no change was found in COX-2-like immunoreactivity, even at the site of seizure genesis. However, upon forebrain seizure generalization, dramatic, ipsilateral increases in COX-2-like immunoreactivity were found in layers II and II of perirhinal, entorhinal and temporal cortex, just dorsal to the perirhinal fissure, coursing from the level of the medial geniculate to the level of the inferior colliculus. No changes in COX-2-like immunoreactivity were found in contralateral cortical regions, retrosplenial cortex, dentate gyrus, subiculum, tenia tectum or inferior colliculus. Thus, initial seizure generalization into the forebrain induces COX-2 expression in a highly specific area of the cerebral cortex.


Spatial and seasonal variability of CH4 in the eastern Gulf of Cadiz (SW Iberian Peninsula).
Methane (CH4) concentrations were measured along three sections of the eastern Gulf of Cadiz (designated "Guadalquivir", "Sancti Petri" and "Trafalgar") during eight cruises in 2014 and 2015. The concentration of CH4 varied from 3.6 to 19.7nmolkg-1 (CH4 saturation percent of 122 and 916%), showing seasonal variation. The highest values were found in December 2014 and November 2015. In most of the sampling area the highest concentration of CH4 was found in subsurface waters at depths close to the thermocline, and in the bottom waters near the coast. The seawater-air flux of CH4 ranged between 0.8 and 59.7μmolm-2d-1, showing seasonal variation in function of the temperature of the surface water. In the "Guadalquivir" and "Sancti Petri" sections, the CH4 fluxes increased with proximity to the coast; this may be a result of continental inputs and CH4 emissions from sediments. The whole study area behaves as a source of CH4 to the atmosphere with mean values of 0.5 and 0.6GgCH4yr-1 in 2014 and 2015, respectively.


[Left main bronchus root prolongation to cure 3 patients whose carina is involved by lung cancer].
Patient whose carina is involved by carcinoma is difficult to treat by surgery. The aim of this study is to evaluate the safety and effectiveness of left main bronchus root prolongation to cure these patients. Three patients with lung carcinoma received tumor, right upper lung and carina excision. And then the trachea and the carina was rebuilt by continuous suture, so that the left main bronchus root was extended by 3 cm, then the middle and lower lobe bronchus were sutured to the right lateral wall of the moved up eminence. All the patients left hospital successfully after three-week treatment, without anastomotic stoma fistula. And they got good quality of life after 30, 21 and 11 months' follow-up, no recurrence or metabasis was found. The left main bronchus root prolongation can preserve the left lateral wall, however, part of the tracheal mucous membrane and arteria trachealis can be protected without injury. It's benifit for making productive cough and lowering complications after operation. The new carinal reconstruction process has definite indication, which refer to patient with normal left main bronchus root and the right inferior segment trachea involved by carcinoma.


Light source is critical to induce glioblastoma cell death by photodynamic therapy using chloro-aluminiumphtalocyanine albumin-based nanoparticles.
Selection of an efficient light source is fundamental in the development of photodynamic therapy (PDT) protocols. However, few studies provide a comparison of different light sources with regard to phototoxic effects. Here, we compared the cell death induced by photoactivation of chloro-aluminiumphtalocyanine (AlClPc)-loaded human serum albumin nanoparticles under irradiation with different light sources: continuous laser (CL), pulsed laser (PL), and light-emitting diode (LED). Cells were exposed to three different AlClPc concentrations (1, 3, and 5μM) and three different light doses (200, 500, and 700mJ/cm2) for each light source. Cell death and differentiation of apoptosis and necrosis pathway were measured by flow cytometry. CL was the best light source for improving the photodynamic action of AlClPc-loaded albumin nanoparticles in glioblastoma cells and avoiding undesirable side effects, especially at low photosensitizer doses (200mJ/cm2). In addition, apoptosis was the main cell death pathway in all evaluated cases (70% for CL, and greater than 50% for PL and LED). In conclusion, the search for optimal light sources and light/photosensitizer doses is a crucial step in improving PDT outcomes and enhancing the clinical translation of PDT.


Tacrolimus (FK506) prevents early retinal neovascularization in streptozotocin-induced diabetic mice.
Diabetic retinopathy is a complex disease that has potential involvement of inflammatory in its pathogenesis. We hypothesized that tacrolimus (FK506), one of the potent immunosuppressive agent, could be effective against diabetic retinopathy, which involves significant inflammation. The aim of the present study was to investigate the effects of FK506 in early retinal changes of streptozotocin-induced diabetic mice. The effect of FK506 treatment (10 μg per eye for one week) was evaluated by TNF-a, VEGF, iNOS and COX-2 protein levels measurement, neovascularization, and the activation of NF-kB in the retina. Increased amounts of cytokines, neovascularization, inflammatory markers and activation of NF-kB were observed in retina from diabetic mice. FK506 treatment significantly lowered retinal TNF-a, VEGF, iNOS and COX-2. Further, treatment with FK506 significantly suppressed diabetes-related neovascularization, as well as the activation of NF-kB. These data demonstrated that FK506 attenuates the degree of retinal inflammation and preserving the neovascularization in early diabetic mice.


Central nervous systemic efficacy of immune checkpoint inhibitors and concordance between intra/extracranial response in non-small cell lung cancer patients with brain metastasis.
Immune checkpoint inhibitors (ICIs) markedly improve the clinical outcomes of advanced non-small-cell lung cancer (NSCLC). However, the intracranial efficacy of ICI is not well elucidated, and previous studies showed discordant outcomes of ICI between intracranial and extracranial diseases. We aimed to evaluate the clinical outcomes and the intracranial and extracranial response of patients with NSCLC and brain metastasis who were treated with ICI in the real-world setting. A total of 55 patients (median age, 63 years [range 42-80]; male, 78%) who had NSCLC with brain metastasis and treated with ICI monotherapy were retrospectively analyzed. We separately assessed the response rates of brain lesions and systemic lesions, and estimated the overall survival (OS) and progression-free survival (PFS). The median OS and overall PFS were 17.0 months (95% CI 10.3-25.6) and 3.19 months (95% CI 2.24-5.03), respectively. The intracranial objective response rate and disease control rate of ICI were 36 and 54%, respectively. Among the 44 patients who showed disease progression, only 32% (n = 14) showed concordant outcomes and 9 patients (20%) showed opposing discordant outcomes. Eight patients continued ICI with local brain therapy after intracranial progression, and their median extracranial PFS and OS were 15 months (95% CI 5.0-not assessed [NA]) and 23.8 months (95% CI 14.7-NA), respectively. ICI monotherapy had a clinically meaningful intracranial efficacy in NSCLC patients with brain metastasis. Watchful waiting and close monitoring without local radiotherapy might be feasible in NSCLC patients with asymptomatic active brain metastasis.


Potential Susceptibility of Six Aquatic Plant Species to Infection by Five Species of Phytophthora.
Investigations of the susceptibility of aquatic plants to species of Phytophthora are limited. Therefore, the objective of this study was to assess the potential susceptibility of six aquatic plant species, frequently used in constructed wetlands or vegetated channels, to infection by five species of Phytophthora commonly found at nurseries in the southeastern United States. In a greenhouse experiment, roots of each plant species (Agrostis alba, Carex stricta, Iris ensata 'Rising Sun', Panicum virgatum, Pontederia cordata, and Typha latifolia) growing in aqueous solutions were exposed to zoospores of each of the species of Phytophthora (Phytophthora cinnamomi, Phytophthora citrophthora, Phytophthora cryptogea, Phytophthora nicotianae, and Phytophthora palmivora). Zoospore presence and activity in solution were monitored with a standard baiting bioassay with rhododendron leaf discs as baits. Experiments were initiated in 2016 and repeated in 2017 and 2018. During the 2016 trials, Phytophthora spp. were not isolated from the roots of any of the plants, but some roots of C. stricta, P. virgatum, and T. latifolia were infected with multiple species of Phytophthora during trials in 2017 and 2018. Presence of plant roots reduced the percentage of rhododendron leaf discs infected by zoospores of four of the species of Phytophthora but not those infected by P. cinnamomi, which suggested that roots of these plants negatively affected the presence or activity of zoospores of these four species of Phytophthora in the aqueous growing solution. Results from this study demonstrated that certain aquatic plant species may be sources of inoculum at ornamental plant nurseries if these plants are present naturally in waterways or used in constructed wetlands treating water flowing off production areas, which could be of concern to plant producers who recycle irrigation water.


Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.
Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.


Maternal risk score for the prediction of fetal inflammatory response syndrome after preterm premature rupture of membranes.
Preterm premature rupture of membranes (PPROM) is common in preterm births. Fetal inflammatory response syndrome (FIRS) is present in nearly 50% of PPROM cases. We created a risk score to predict FIRS using maternal factors after PPROM. We conducted a retrospective study of singleton pregnancies complicated by PPROM that resulted in delivery at 23-35 weeks of gestation. Antepartum maternal factors and umbilical cord blood interleukin-6 (IL-6) data were analyzed. FIRS was defined as IL-6 > 11 pg/mL. Umbilical cord blood IL-6 and maternal blood data within 24 h before parturition were available for 158 cases; 66 were diagnosed with FIRS (41.8%; median IL-6, 57.55 pg/mL). We created a risk score (FIRS score) comprising expected delivery weeks (≤30 weeks), maternal C-reactive protein (≥1.2 mg/dL), maternal white blood cell count (≥13 000/μL), corticosteroid use (none) and PROM latency period (≥3 days) from the multivariate logistic regression model predicting FIRS. Receiver operating characteristic curve analysis of the score produced the following results: area under the curve, 0.82; 95% CI, 0.76-0.89; cut-off value, 7.5; sensitivity, 89%; specificity, 63%; positive predictive value, 63% and negative predictive value, 89%. The probability of FIRS according to the categories of the FIRS score was 11% for those with a score of 0-7, 50% for a score of 8-15, and 88% for a score of 16-22. The devised maternal risk score could predict FIRS and be helpful to decide the delivery timing for the cases of PPROM.


Differences between lung adenocarcinoma and squamous cell carcinoma in histological distribution of residual tumor after induction chemoradiotherapy.
To facilitate dose planning for convergent beam radiotherapy in non-small cell lung cancer (NSCLC), tumor response and histological distribution of residual tumors after induction chemoradiotherapy (ICRT) were compared between adenocarcinoma (AD) and squamous cell carcinoma (SQ). Ninety-five patients with N1-2 or T3-4 NSCLC were treated with ICRT followed by surgery; 55 had AD and 40 had SQ. For the evaluation of distribution of residual tumors, the location of the external margin of residual tumors was assessed on surgical materials as follows: radius of whole tumor ("a"); distance between the center of tumor and the external margin of residual tumor ("b"); and its location ("b/a"). Of the 55 AD cases, 8 (15%) showed pathological complete remission, which was significantly less frequent than 22 of 40 SQ cases (55%) (p < 0.001). AD showed the residual tumors at the most periphery of tumor (b/a = 1.0) more frequently than SQ, i.e., 39/55 (71%) versus 6/40 (15%), respectively (p < 0.001). Even in 65 cases other than the pathological complete remission, external margins in 47 AD cases located more periphery than those in 18 SQ cases, of which mean b/a values were 0.97 ± 0.17 and 0.70 ± 0.29, respectively (p < 0.001). AD showed worse tumor response to ICRT than SQ. After ICRT, AD remained at the periphery of primary tumor more frequently than SQ. It seems that, also in the convergent beam radiotherapy, the periphery part of AD would be more resistant than that of SQ.


Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress.
Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group. The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.