Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Part 2: Central administration of 1-methyl-4-phenylpyridinium.
There are marked species differences in susceptibility to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice are sensitive, whereas rats are relatively insensitive to MPTP. In these two species, the effects of peripherally administered MPTP or intrastriatally infused 1-methyl-4-phenylpyridinium (MPP+) were examined to identify potential underlying mechanisms responsible for their difference in susceptibility to MPTP. In vivo intrastriatal microdialysis and an MPP+ 2-day test/challenge paradigm were used to monitor dopamine efflux as an indicator of the neurotoxic effects of MPTP or MPP+. By using this method, the EC50 for neurotoxicity by an intrastriatal infusion of MPP+ in mice was 0.4 mM, whereas it was 10-fold higher in rats (4.3 mM). In addition, by using the traditional postmortem examination, neostriatal dopamine was depleted markedly in mice (> or = 80%), but only depleted marginally in rats in which MPP+ was infused into the neostriatum. These data indicate that rats are relatively insensitive to MPTP as compared to mice, because they are less sensitive to MPP+ whether it is formed in vivo from MPTP administered systemically or administered directly into neostriata. Thus, there appears to be a fundamental difference in the susceptibility of the nigrostriatal systems in these two species to the neurotoxic consequences of MPP+ exposure.


Cognitive-behavioral therapy for patients with post-COVID-19 condition (CBT-PCC): a feasibility trial.
The post-COVID-19 condition describes the persistence or onset of somatic symptoms (e.g. fatigue) after acute COVID-19. Based on an existing cognitive-behavioral treatment protocol, we developed a specialized group intervention for individuals with post-COVID-19 condition. The present study examines the feasibility, acceptance, and effectiveness of the program for inpatients in a neurological rehabilitation setting. The treatment program comprises eight sessions and includes psychoeducational and experience-based interventions on common psychophysiological mechanisms of persistent somatic symptoms. A feasibility trial was conducted using a one-group design in a naturalistic setting. N = 64 inpatients with a history of mild COVID-19 that fulfilled WHO criteria for post-COVID-19 condition were enrolled. After each session, evaluation forms were completed and psychometric questionnaires on somatic and psychopathological symptom burden were collected pre- and post-intervention. The treatment program was well received by participants and therapists. Each session was rated as comprehensible and overall satisfaction with the sessions was high. Pre-post effect sizes (of standard rehabilitation incl. new treatment program; intention-to-treat) showed significantly reduced subjective fatigue (p < 0.05, dav = 0.33) and improved disease coping (ps < 0.05, dav = 0.33-0.49). Our results support the feasibility and acceptance of the newly developed cognitive-behavioral group intervention for individuals with post-COVID-19 condition. Yet, findings have to be interpreted cautiously due to the lack of a control group and follow-up measurement, the small sample size, and a relatively high drop-out rate.


Using multiple biomarkers and determinants to obtain a better measurement of oxidative stress: a latent variable structural equation model approach.
Since oxidative stress involves a variety of cellular changes, no single biomarker can serve as a complete measure of this complex biological process. The analytic technique of structural equation modeling (SEM) provides a possible solution to this problem by modelling a latent (unobserved) variable constructed from the covariance of multiple biomarkers. Using three pooled datasets, we modelled a latent oxidative stress variable from five biomarkers related to oxidative stress: F2-isoprostanes (FIP), fluorescent oxidation products, mitochondrial DNA copy number, γ-tocopherol (Gtoc) and C-reactive protein (CRP, an inflammation marker closely linked to oxidative stress). We validated the latent variable by assessing its relation to pro- and anti-oxidant exposures. FIP, Gtoc and CRP characterized the latent oxidative stress variable. Obesity, smoking, aspirin use and β-carotene were statistically significantly associated with oxidative stress in the theorized directions; the same exposures were weakly and inconsistently associated with the individual biomarkers. Our results suggest that using SEM with latent variables decreases the biomarker-specific variability, and may produce a better measure of oxidative stress than do single variables. This methodology can be applied to similar areas of research in which a single biomarker is not sufficient to fully describe a complex biological phenomenon.


Seroepidemiological survey of the prevalence of antibodies to a strain of human calicivirus.
Batches of pooled immune globulins and sera were tested by immune electron microscopy (IEM) for the presence of antibodies to a strain of human calicivirus (HCV, UK1). The results show that this strain of HCV is prevalent throughout many parts of the world and that the majority of the population experience infection by the age of 12 years. The survey carried out in the United Kingdom indicates that the presence of maternal antibody correlates with some degree of protection during the first few weeks of life; the peak incidence of cases and acquisition of antibody occur between 3 months and 6 years. Tests on sera from Japan show a similar pattern of acquisition of antibodies and demonstrate that infection with more than one strain of HCV commonly occurs during childhood.


The effect of interleukin-6 on L-selectin levels on polymorphonuclear leukocytes.
Interleukin-6 (IL-6) shortens the transit time of polymorphonuclear leukocytes (PMN) through the marrow and accelerates their release into the circulation. In contrast to other inflammatory stimuli, this response is associated with a decrease in L-selectin levels on circulating PMN. The present study was designed to determine the effect of IL-6 on L-selectin levels of PMN in rabbits. Recombinant human IL-6 (2 microg/kg) caused a decrease in L-selectin levels on circulating PMN 3 to 12 h after treatment (P < 0.05). L-selectin levels decreased on PMN already in the circulation for up to 4 h (P < 0.05), on PMN released from the marrow posttreatment for up to 12 h (P < 0.01) and on PMN in the marrow for up to 6 h (P < 0.05) after IL-6 treatment. We conclude that IL-6 decreases L-selectin levels on circulating PMN by demarginating PMN with low levels of L-selectin and by releasing PMN from the marrow with low levels of L-selectin. We postulate that this prolonged downregulation of L-selectin on circulating PMN could influence their recruitment into inflammatory sites.


Effects of captopril on blood pressure and respiratory function compared to verapamil in patients with hypertension and asthma.
Seventeen adult patients with moderate and stable bronchial asthma and established essential hypertension (WHO I or II) were evaluated in a randomized, double-blind, crossover study of the effects of captopril (50-100 mg/day) and verapamil (160-240 mg/day) on blood pressure, orthostatic reactions, respiratory function, and asthmatic symptoms. The effect of both drugs on blood pressure was significant. Blood pressure (mean of 161/98 mm Hg initially) decreased to a mean of 147/90 and 160/91 mm Hg on captopril and verapamil, respectively, with normal orthostatic changes. There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% of FVC (MEF50), or peak expiratory flow (PEF) measurements at the end of each treatment period. The subjective severity of asthma did not change significantly during the trial. No significant cough symptoms were reported on captopril.


Program evaluation of a telepsychiatry service for older adults connecting a university-affiliated geriatric center to a rural psychogeriatric outreach service in Northwest Ontario, Canada.
Weekly telepsychiatry consultations have been provided since 2002 to six communities in Northwest Ontario. Staff from a single community psychogeriatric outreach service who work within these communities facilitate the referrals. The program evaluation included (a) a chart review of the last 100 referrals, (b) analysis of patient and staff evaluations, (c) a survey mailed to all physicians in referring communities, and (d) three focus groups of staff working in local community agencies. The mean age at the time of consultation was 76.7 years. Sixty-eight percent of patients were females. The most frequent diagnoses were dementia (54%), depression (28%), and mild cognitive impairment (19%). The most frequent medication recommendations were antidepressants or cholinesterase inhibitors. Two hundred ninety-four patient assessments and case consultations were carried out between 2002 and 2009. Post-session evaluation surveys rated the provision of information, whether objectives were met, and overall usefulness of recommendations. The mean scores for these questions on a 5-point scale were between 4.6 and 4.85. Referring physicians were confident and satisfied with the recommendations made for their patients. All planned to continue to use telepsychiatry as a care option for the future. The focus groups added useful information about challenges and potential barriers to utilizing the program. The program was rated as being highly valued across all modalities of evaluation. Members of the referring team believe that access to a geriatric psychiatrist has broadened the team's knowledge base, its use of assessment tools, and increased their ability to better construct their patients' treatment plans.


Effect of cholecystokinin-octapeptide on opossum lower esophageal sphincter.
We evaluated the action of cholecystokini-octapeptide (CCK-OP) on lower esophageal sphincter (LES) pressure in the opossum. LES pressure was recorded by an infused sleeve device that straddled the sphincter, whereas intraluminal esophageal pressure and gastric pressure were recorded via conventional manometric catheters. Progressive intravenous pulse doses of CCK-OP caused 1) graded increases in LES pressure, 2) circular and longitudinal smooth muscle contraction in esophageal body, and 3) mild increases in intragastric pressure. Pressor effect of CCK-OP on the LES was weakly antagonized by tetrodotoxin (TTX), but not by atropine, phentolamine, or pyrilamine. TTX antagonism of CCK-OP appeared to be nonspecific because TTX also partially antagonized LES contractions induced by pentagastrin, substance P, and bethanechol. We conclude that CCK-OP at doses that cause LES relaxation in other species induces LES contraction in the opossum. This pressor effect appears to be elicited by a direct action of the hormone on LES smooth muscle.


Insights into drug resistance mechanisms in Clostridium difficile.
The incidence of Clostridium difficile infection has been elevated and becoming common in hospitals worldwide. Although antibiotics usually serve as the primary treatment for bacterial infection including C. difficile infection, limitations and failures have been evident due to drug resistance. Antibiotic resistance in C. difficile has been recognized as one of the most important factors to promote the infection and increase the level of severity and the recurrence rate. Several outbreaks in many countries have been linked to the emergence of hypervirulent drug-resistant strains. This pathogen harbours various mechanisms against the actions of antibiotics. The present study highlights three main drug-resistant strategies in C. difficile including drug inactivation, target modification and efflux pump. Other mechanisms that potentially contribute to drug-resistant traits in this organism are also discussed.


Cost Effectiveness of Inhaled Mannitol (Bronchitol®) in Patients with Cystic Fibrosis.
Inhaled mannitol (Bronchitol®) is licensed in Australia as a safe and efficacious addition to best supportive care in patients with cystic fibrosis. The objective of this study was to assess the cost effectiveness of inhaled mannitol (in addition to best supportive care) in the Australian setting from the perspective of a government-funded national healthcare system. A probabilistic patient-level simulation Markov model estimated life-time costs and outcomes of mannitol when added to best supportive care, compared with best supportive care alone in patients aged 6 years and older. We estimated treatment-related inputs (initial change in percentage of predicted forced expiratory volume, relative reduction in severe pulmonary exacerbations, and treatment discontinuations) from two phase III trials. Longer term natural history rates of predicted forced expiratory volume decline over time and severe pulmonary exacerbation rates for best supportive care were taken from Australian CF registries. The utility value for the cystic fibrosis health state was as measured in the trials using the Health Utility Index, whereas the impact of pulmonary exacerbations and lung transplantation on utility was ascertained from the published literature. The underlying cost of managing cystic fibrosis, and the cost associated with pulmonary exacerbations and transplantations was taken from published Australian sources. The addition of inhaled mannitol to best supportive care resulted in a discounted cost per quality-adjusted life-year of AU$39,165. The result was robust with 77% of probabilistic sensitivity analysis samples below a willingness-to-pay threshold of AU$45,000/quality-adjusted life-year. Benchmarked against an implicit Australian willingness-to-pay threshold for life-threatening diseases, our model suggests inhaled mannitol provides a cost-effective addition to best supportive care in patients with cystic fibrosis, irrespective of concomitant dornase alfa use.


Visible-Light-Triggered Directly Reductive Arylation of Carbonyl/Iminyl Derivatives through Photocatalytic PCET.
The first visible-light-mediated radical-radical cross-coupling strategy that enables the direct arylation of carbonyl/iminyl derivatives in the presence of Et3N has been realized. Such an atom-economical protocol furnishes a broad scope of arylation products such as secondary/tertiary alcohols and amines via a PCET process that facilitates the challenging reduction of C═X (X = O, N). Mechanistic investigation indicates two photocatalytic redox cycles were involved in the process, and Et3N was proved to serve as a dual reductant and proton donor. Moreover, the isolated byproducts and controlled experiments could be considered as powerful supporting evidence for our hypothesis.


What's new in clinical obstetric anesthesia in 2015?
Each calendar year the Society for Obstetric Anesthesia and Perinatology invites an individual to conduct a review of the medical literature, identifying clinically relevant publications of interest to the obstetric anesthesia provider. This report of that effort covers the publications from 2015 and includes the categories of anesthesia and analgesia, complications of neuraxial procedures, and the effects of anesthesia on the fetus. Neuraxial procedures represent the foundation of obstetric anesthesia; advances in anesthesia and analgesia include novel modes of administration, and refinements in care of the medically complex patient. In addition to labor analgesia, investigations into post-cesarean recovery address challenges in pain control, patients with obstructive sleep apnea, and treatment protocols intended to improve patient care, notably an enhanced-recovery pathway. Because complications are inevitable, this review identifies investigations on the more common complications of neuraxial procedures, such as hypotension, maternal and fetal bradycardia, and post-dural puncture headache. There were several innovative reports attempting to address these complications, including the use of norepinephrine infusion for the prevention of spinal-induced hypotension, ephedrine for the prevention of fetal bradycardia after combined spinal-epidural analgesia, and pharmacologic treatment of post-dural puncture headache. Not all of these treatments were successful. Finally, there are potential effects of anesthesia on the fetal/neonatal brain, much of which remains poorly defined. An analysis of recent papers suggests that epidural fever is not an independent cause of adverse neurologic fetal injury. On the other hand, evidence continues to grow to support the hypothesis that anesthetic drugs impact neonatal neurologic outcome.


Prior irinotecan exposure does not preclude benefit to liposomal irinotecan in patients with metastatic pancreatic ductal adenocarcinoma.
Subgroup analyses of the NAPOLI-1 study identified that among patients who were irinotecan naïve prior to entering the clinical trial, a survival benefit was observed between the study arm and control arm. This treatment benefit was not observed among those previously exposed to irinotecan. This study sought to understand the impact of prior exposure to irinotecan on clinical outcomes among patients treated with liposomal irinotecan in the real-world setting. This retrospective observational study utilized a nationwide electronic health record (EHR)-derived deidentified database. Data for adult patients with mPDAC treated with liposomal irinotecan-based regimens between January 2016 and October 2020 were analyzed. Patient characteristics, overall survival (OS), and progression-free survival (PFS) were assessed. Cox proportional hazard methods were used to calculate hazard ratios (HRs). HRs were adjusted for demographics and relevant clinical covariates. Six hundred and seventy-five patients with mPDAC treated with a liposomal irinotecan-based regimen were included. The unadjusted OS HR was 1.3 (95% CI: 1.1-1.6, p < 0.001) and unadjusted PFS was HR 1.4 (95% CI: 1.2-1.7, p < 0.001). After adjustment for baseline characteristics, the adjusted OS HR was 1.0 (95% CI: 0.8-1.3, p = 0.8836) and the adjusted PFS HR was 1.1 (95% CI: 0.8-1.4, p = 0.5626). Prior irinotecan was not found to be a significant predictor of patient outcomes in those later treated with liposomal irinotecan. Thus, the results may inform the rationale for utilizing liposomal irinotecan combination therapy following prior irinotecan exposure in mPDAC, in particular where the prior irinotecan exposure was more distant in time.


Preparation of a 3D printable high-performance GelMA hydrogel loading with magnetic cobalt ferrite nanoparticles.
Osteosarcoma remains a worldwide concern due to the poor effectiveness of available therapies in the clinic. Therefore, it is necessary to find a safe and effective therapy to realize the complete resection of osteosarcoma and reconstruction of the bone defect. Magnetic hyperthermia based on magnetic nanoparticles can kill tumor cells by raising the temperature without causing the side effects of conventional cancer treatments. This research aims to design a high-performance magnetic hydrogel composed of gelatin methacrylate and highly magnetic cobalt ferrite (CFO) nanoparticles for osteosarcoma treatment. Specifically, CFO is surface functionalized with methacrylate groups (MeCFO). The surface modified CFO has good biocompatibility and stable solution dispersion ability. Afterward, MeCFO nanoparticles are incorporated into GelMA to fabricate a three-dimensional (3D) printable MeCFO/GelMA magnetic hydrogel and then photocross-linked by UV radiation. MeCFO/GelMA hydrogel has high porosity and swelling ability, indicating that the hydrogel possesses more space and good hydrophily for cell survival. The rheological results showed that the hydrogel has shear thinning property, which is suitable as a bioprinting ink to produce desired structures by a 3D printer. Furthermore, 50 μg/mL MeCFO not only decreases the cell activity of osteosarcoma cells but also promotes the osteogenic differentiation of mBMSCs. The results of the CCK-8 assay and live/dead staining showed that MeCFO/GelMA hydrogel had good cytocompatibility. These results indicated that MeCFO/GelMA hydrogel with potential antitumor and bone reconstruction functions is a promising therapeutic strategy after osteosarcoma resection.


Revelations in our own backyard: Chandra's unique Galactic Center discoveries.
Before the launch of Chandra, our Galactic Center supermassive black hole, Sgr A*, had never been positively identified outside the radio bands. A great deal has changed in the past decade, starting with the discovery that our own backyard harbors a very weak, yet clearly active, galactic nucleus. I will review how this revelation has been a boon for accretion studies around black holes in general and has helped us place our own Galaxy in context within the active galactic nuclei (AGN) zoology. Chandra's exquisite resolution has also unveiled entirely new populations of faint sources and transients, as well as regions of extreme gas dynamics and hints of prior, more typical AGN-like activity in our Galactic Center.


A rare case of pancreatic mediastinal pseudocyst.
Pancreatic pseudocysts are the most common cystic lesions of the pancreas, accounting for 75-80% of such masses. Pancreatic pseudocyst with mediastinal extension is a rare clinical entity and only a handful cases report on dysphagia associated with mediastinal pseudocyst formation.1 We present a case of pancreatic mediastinal pseudocyst that presented with palpitations and dysphagia. Demonstration of cystic lesion in relation to the pancreas on ultrasound and mediastinal extension of the cyst on CT suggested the diagnosis.


Optical microscopic study on a novel morphological classification method of multiple diagnostic features of Sarcoptes scabiei var. hominis.
Optical microscopy is the gold standard technique used to confirm the diagnosis of scabies. Multiple diagnostic features of the pathogen Sarcoptes scabiei var. hominis (S. scabiei) can be identified under a microscope and classified into 3 categories: mites, eggs and fecal pellets. However, mite and eggshell fragments can also be observed, which have been ignored in the 2020 International Alliance for the Control of Scabies (IACS) Criteria and by most researchers. In this study, we propose a novel morphological classification method that classifies multiple diagnostic features into 5 categories and 7 subcategories. Our results revealed that 65.2% (1893 of 2896) of the positive cases were confirmed through the identification of mites, eggs or fecal pellets, whereas up to 34.6% (1003 of 2896) of the positive cases were confirmed through the identification of mite or eggshell fragments. Therefore, the important diagnostic values of mite and eggshell fragments should be emphasized. Importantly, for the first time, mite and eggshell fragments were classified into 7 subcategories, some of which are easily ignored or confused with contaminating artefacts. We believe that this novel morphological classification method will be beneficial for operator training in interpreting slides and in improving the 2020 IACS Criteria.


Copper ions inhibit S-adenosylhomocysteine hydrolase by causing dissociation of NAD+ cofactor.
S-Adenosylhomocysteine hydrolase (SAHH) regulates biomethylation and homocysteine metabolism and thus is an attractive target in drug design studies. SAHH has been shown to be a copper binding protein in vivo; however, the structure and catalytic mechanism of SAHH exclude a role for Cu2+. In the present work, we studied the mechanism of inhibition of SAHH activity by Cu2+. The experimental results showed that Cu2+ inhibited SAHH activity in a noncompetitive manner. Binding of Cu2+ to SAHH resulted in the release of NAD+ cofactors, explaining the loss of the enzymatic activity of SAHH. Further investigation by an ESR probe and computational simulation suggested that Cu2+ could bind at the central channel and interrupt the subunit interactions of SAHH, resulting in a large decrease in affinity to the NAD+ cofactor. This effect of Cu2+ resembled that of enzyme mutations at the C-terminal domain or Asp244 [Komoto, J., Huang, Y., Gomi, T., Ogawa, H., Takata, Y., Fujioka, M., and Takusagawa, F. (2000) Effects of site-directed mutagenesis on structure and function of recombinant rat liver S-adenosylhomocysteine hydrolase. Crystal structure of D244E mutant enzyme, J. Biol. Chem. 275, 32147-32156]. The mechanism of action of Cu2+ on SAHH suggested a possible regulative role for Cu2+ on the intracellular activity of SAHH. This could be helpful in understanding the biological effects of copper compounds and suggest a potential coupling mechanism between biomethylation and the redox states of cells.


Therapists perspectives on the effective elements of consultation following training.
Consultation is an effective implementation strategy to improve uptake of evidence-based practices for youth. However, little is known about what makes consultation effective. The present study used qualitative methods to explore therapists perspectives about consultation. We interviewed 50 therapists who had been trained 2 years prior in cognitive-behavioral therapy for child anxiety. Three themes emerged regarding effective elements of consultation: (1) connectedness with other therapists and the consultant, (2) authentic interactions around actual cases, and (3) the responsiveness of the consultant to the needs of individual therapists. Recommendations for the design of future consultation endeavors are offered.


The development and evaluation of individualized templates to assist transoral C2 articular mass or transpedicular screw placement in TARP-IV procedures: adult cadaver specimen study.
The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure. A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories. There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth. It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications.


Effects of quinupristin/dalfopristin on vasomotor tone in the intact peripheral microcirculation.
The purpose of this study was to determine whether quinupristin/dalfopristin modulates vasomotor tone in the intact peripheral microcirculation. Using intravital microscopy, we found that superfusion of quinupristin/dalfopristin (120 mg/L) on the intact hamster cheek pouch microcirculation had no significant effects on arteriolar diameter. In addition, superfusion of quinupristin/dalfopristin (120 mg/L) had no significant effects on vasodilation evoked by bradykinin and acetylcholine, two endothelium-dependent agonists, or by vasoactive intestinal peptide, an endothelium-independent agonist, on to the cheek pouch. Collectively, these data indicate that quinupristin/dalfopristin has no significant effects on vasomotor tone in the intact peripheral microcirculation.


DNA analysis of a non-native lineage of Sinanodonta woodiana species complex (Bivalvia: Unionidae) from Middle Asia supports the Chinese origin of the European invaders.
The Sinanodonta woodiana species complex includes several cryptic species-level phylogenetic lineages, the taxonomic placement of which is unclear. Here, we present the results of molecular analyses of a Sinanodonta sample from Middle Asia (Uzbekistan). The COI haplotype of the Uzbekistan lineage is similar to those of invasive Sinanodonta populations from Europe, Russia and Myanmar. We show that the non-native Sinanodonta flocks in Europe and Middle Asia originated from a single source population in China. Our results reveal that the Sinanodonta woodiana species complex comprises at least six distinct biological species: S. cf. gibba (=temperate invasive lineage), S. cf. woodiana (=tropical invasive lineage), S. schrenkii (=S. amurensis), S. ovata, S. jourdyi, and S. lucida, and two phylogenetic lineages with uncertain taxonomic names.


Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms.
The varied aspects of spread of appendiceal neoplasms are reviewed with emphasis on the often clinically dramatic phenomenon known as pseudomyxoma peritonei, a term mostly used to describe grossly evident mucin within the peritoneal cavity. The majority of cases of pseudomyxoma peritonei result from tumors primary in the appendix, which are usually low-grade. On microscopic examination pseudomyxoma peritonei is typically characterized by large aggregates of mucin which may be relatively acellular or cellular containing strips of mucinous epithelium, mucinous epithelium encircling glands and cysts, or aggregates of mucinous epithelium lying within mucin pools. High-grade adenocarcinoma of the appendix may spread to the omentum and peritoneal surfaces without grossly striking mucin deposition and resemble spread of other high-grade gastrointestinal adenocarcinomas. In many cases of pseudomyxoma peritonei in females there is involvement of one, or more often, both ovaries. The size of the ovarian neoplasms characteristically dwarfs the often relatively unremarkable appearing appendix in these cases. The ovaries are typically multilocular, although one locule may dominate, and in cases in which the primary is a low-grade appendiceal mucinous neoplasm often have a "jelly-like" consistency. In cases of spread of frank adenocarcinomas the ovarian metastases typically have a more solid, albeit still somewhat gelatinous consistency. Microscopic examination of the ovaries typically shows surface involvement, a characteristic of spread to the ovaries in general, and the glands and cysts that replace most or all of the parenchyma are typically lined by tall mucin-rich cells with, in many cases, relatively bland microscopic features. In cases of frank adenocarcinoma, the tumors may mimic closely a primary mucinous adenocarcinoma of the ovary. Spread to the ovaries may also be seen in cases of frank intestinal-type adenocarcinoma primary in the appendix and the uncommon signet ring cell carcinoma of the appendix, the latter being one cause of the Krukenberg tumor. Occasional cases are reported in the literature of ovarian spread of goblet cell carcinoid tumor of the appendix, but in our opinion most of the primary tumors in those cases are better classified as adenocarcinomas, usually dominantly of signet-ring cell type, albeit sometimes with focal neuroendocrine differentiation. Other interesting aspects of spread of appendiceal neoplasms include to the lining of the uterus and the fallopian tube. In yet other cases the tumors may present clinically as incidentally discovered mucinous aggregates within hernia sac specimens or as a scrotal mass.


Biopsy of small kidneys: A safe and a useful guide to potentially treatable kidney disease.
Over the past four years, all patients with unexplained rapid progression of their renal disease were subjected to kidney biopsy, despite their small size (<9 cm), to define its etiology. Children, pregnant women, morbidly obese patients, and those with an unstable cardiovascular state, septicemia, bleeding diathesis as well as those kidney size with size <6 cm were excluded from the study. Doppler ultrasound was used to exclude renovascular/ischemic nephropathy. The procedure was performed by an interventional radiologist using a biopsy gun technique and under ultrasound guidance. The actual diagnosis was established in 29 cases while seven had advanced sclerosing glomerulonephritis. Eleven cases had evidence of vasculitis, of which two were due to polyarteritis nodosa and two were due to crescentic immunoglobulin A disease. The remaining patients had a secondary form of focal segmental glomerulosclerosis (n = 4), interstitial nephritis (n = 4), malignant nephro-angiosclerosis (n = 2), and single patient with primary hyperoxaluria, light chain cast nephropathy, amyloidosis, and thrombotic microangiopathy. All, except eight with advanced glomerulosclerosis, had improved or became stable with specific treatment. Our study shows that biopsy of small-sized kidneys, in patients with unexplained renal deterioration, is safe, and its diagnostic value can improve their morbidity and even mortality.


Utility of transesophageal echocardiography during orthotopic liver transplantation: A narrative review.
Orthotopic liver transplantation (OLT) is the standard of care for patients suffering from end stage liver disease (ESLD). This is a high-risk procedure with the potential for hemorrhage, large shifts in preload and afterload, and release of vasoactive mediators that can have profound effects on hemodynamic equilibrium. In addition, patients with ESLD can have preexisting coronary artery disease, cirrhotic cardiomyopathy, porto-pulomary hypertension and imbalanced coagulation. As cardiovascular involvement is invariable and patient are at an appreciable risk of intraoperative cardiac arrest, Trans esophageal echocardiography (TEE) is increasingly becoming a routinely utilized monitor during OLT in patients without contraindications to its use. A comprehensive TEE assessment performed by trained operators provides a wealth of information on baseline cardiac function, while a focused study specific for the ESLD patients can help in prompt diagnosis and treatment of critical events. Future studies utilizing TEE will eventually optimize examination safety, quality, permit patient risk stratification, provide intraoperative guidance, and allow for evaluation of graft vasculature.


Molecular logic: a half-subtractor based on tetraphenylporphyrin.
Spectroscopic changes from a solution of the amphophile 5,10,15,20-tetraphenylporphyrin in N,N-dimethylformamide using inputs of acid (HClaq) and base (KOBut) are interpreted as XOR and INHIBIT logic operations. The combination of these two operations gives rise to a device that acts as a molecular half-subtractor.


Microwave spectrum, structural parameters, and quadrupole coupling for 1,2-dihydro-1,2-azaborine.
The first microwave spectrum for 1,2-dihydro-1,2-azaborine has been measured in the frequency range 7-18 GHz, providing accurate rotational constants and nitrogen and boron quadrupole coupling strengths for three isotopomers, H(6)C(4)(11)B(14)N, H(6)C(4)(10)B(14)N, and H(5)DC(4)(11)B(14)N. The measured rotational constants were used to accurately determine coordinates for the substituted atoms and provide sufficient data to determine most of the important structural parameters for this molecule. The spectra were obtained using a pulsed beam Fourier transform microwave spectrometer, with sufficient resolution to allow accurate measurements of (14)N, (11)B, and (10)B nuclear quadrupole hyperfine interactions. High-level ab initio calculations provided structural parameters and quadrupole coupling strengths that are in very good agreement with measured values. The rotational constants for the parent compound are A = 5657.335(1), B = 5349.2807(5), and C = 2749.1281(4) MHz, yielding the inertial defect Delta(0) = 0.02 amu x A(2) for the ground-state structure. The observed near-zero and positive inertial defect clearly indicates that the molecular structure of 1,2-dihydro-1,2-azaborine is planar. The least-squares fit analysis to determine the azaborine ring structure yielded the experimental bond lengths and 2sigma errors R(B-N) = 1.45(3) A, R(B-C) = 1.51(1) A, and R(N-C) = 1.37(3) A for the ground-state structure. Interbond angles for the ring were also determined. An extended Townes-Dailey population analysis of the boron and nitrogen quadrupole coupling constants provided the valence p-electron occupancy p(c) = 0.3e for boron and p(c) = 1.3e for nitrogen.


Covalent EGFR Inhibitors: Binding Mechanisms, Synthetic Approaches, and Clinical Profiles.
Being overexpressed in several types of cancer, the epidermal growth factor receptor (EGFR) is considered one of the key therapeutic targets in oncology. Although many first-generation EGFR inhibitors had been FDA approved for the treatment of certain types of cancer, patients soon developed resistance to these reversible ATP competitive inhibitors via mutations in the kinase domain of EGFR. A new trend was adopted to design covalent irreversible inhibitors, that is, second- and third-generation inhibitors. Second-generation inhibitors can inhibit the mutant forms but, unfortunately, they had dose limiting side effects due to wild-type EGFR inhibition. Third-generation inhibitors emerged shortly, which were capable of inhibiting the mutant forms exclusively while sparing the wild type. Many other strategies have also been developed to reduce the risk of covalent interactions with off-targets, thus improving the pharmacokinetic and/or pharmacodynamic profile of the antiproliferative agents. In this review, we focused mainly on second- and third-generation EGFR inhibitors, their binding mechanisms (either docking studies or co-crystallized structures), their synthetic approaches, clinical profiles, and limitations.


Treatment outcomes in patients with third-generation cephalosporin-resistant Enterobacter bacteremia.
Infections with resistant Enterobacter spp. are increasingly described, yet data on outcomes associated with these infections are limited. A retrospective cohort study was conducted to investigate outcomes of hospitalized patients with third-generation cephalosporin-resistant (CR) Enterobacter bacteremia. Cephalosporin resistance was detected using cefotaxime and cefpodoxime. Patients with Enterobacter spp. bacteremia from January 2006 through February 2008 defined the population. We defined cases as those with CR isolates; controls were patients with bacteremia due to non-CR isolates. Treatment failure was defined as persistence of the presenting signs of infection 72 h after initial culture collection. Of the 95 Enterobacter cases identified, 31 (33%) were CR. CR cases were significantly associated with treatment failure (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.14-6.94). This association was not seen after adjustment for age, simplified acute physiology score (SAPS II), and inappropriate empiric antibiotic therapy. Inappropriate empiric therapy (adjusted OR 3.86, 95% CI 1.32-11.31) and SAPS II score (adjusted OR 1.09, 95% CI 1.02-1.16) were significantly associated with treatment failure in the multivariate analysis. Third-generation cephalosporin-resistant Enterobacter bacteremia is associated with treatment failure due to receipt of inappropriate empiric antibiotic therapy and severity of illness.


Assessing the Nurturing Care Content of UNICEF's Community Infant and Young Child Feeding Counselling Package: Gaps, Best Practices, and Lessons Learned.
The United Nations Children's Fund (UNICEF) Community Infant and Young Child Feeding Counselling Package (C-IYCF CP) is used globally for infant and young child feeding (IYCF) counseling. With the C-IYCF CP last updated 8 y ago, mapping existing nurturing care content, identifying gaps, and documenting current country-level changes offers a unique opportunity to guide recommendations to strengthen the nurturing care content of this package. The primary study aims were to: 1) identify and map existing nurturing care content within UNICEF's C-IYCF CP, 2) identify gaps related to nurturing care or feeding elements within the C-IYCF CP, 3) identify country-level nurturing care adaptations to the C-IYCF CP, and 4) identify best practices and lessons learned from country adaptations that can be recommended for inclusion in the C-IYCF CP. The assessment included 4 phases: 1) conduct an iterative process to identify and map nurturing care elements within the C-IYCF CP using a codebook explicitly developed for this assessment; 2) identify gaps in the C-IYCF CP; 3) apply the codebook to IYCF packages from 11 countries, revise, then finalize the codebook; and 4) identify and interview key informants from 4 countries whose IYCF packages had the most comprehensive nurturing care content plus 1 country where health care professionals make routine mother-child home visits. The C-IYCF CP contained limited nurturing care content, especially around safety/security and early learning. All 5 countries interviewed had systematically identified and included priority nurturing care content in each package, yet content level varied. Two countries were also incorporating information technology into the training and delivery of the C-IYCF CP. Existing country-level best practices can address nurturing care elements missing from UNICEF's C-IYCF CP. Sharing these practices can allow countries to make context-driven, evidence-informed decisions on the nurturing care content to prioritize.


Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin-resistant rats.
Insulin resistance (IR) impairs vascular responses in peripheral arteries. However, the effects of IR on cerebrovascular control mechanisms are completely unexplored. We examined the vascular function of isolated middle cerebral arteries (MCAs) from fructose-fed IR and control rats. Endothelium-dependent vasodilation elicited by bradykinin (BK) was reduced in IR compared with control MCAs. Maximal dilation to BK (10(-6) M) was 38 +/- 3% (n = 13) in control and 19 +/- 3% (n = 10) in IR arteries (P < 0.01). N(omega)-nitro-L-arginine methyl ester (L-NAME; 10 microM) decreased responses to BK in control arteries by approximately 65% and inhibited the already reduced responses completely in IR MCAs. Indomethacin (10 microM) reduced relaxation to BK in control MCAs by approximately 40% but was largely ineffective in IR arteries. Combined L-NAME and indomethacin treatments eliminated the BK-induced dilation in both groups. Similarly to BK, endothelium-mediated and mainly cyclooxygenase (COX)-dependent dilation to calcium ionophore A23187 was reduced in IR arteries compared with controls. In contrast, vascular relaxation to sodium nitroprusside was similar between the IR and control groups. These findings demonstrate that endothelium-dependent dilation in cerebral arteries is impaired in IR primarily because of a defect of the COX-mediated pathways. In contrast, nitric oxide-mediated dilation remains intact in IR arteries.


Characterization of five partial deletions of the factor VIII gene.
Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, we have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes.


Combination therapy with mitomycin C (NSC-26980), 5-fluorouracil (NSC-19893), and cytosine arabinoside (NSC-63878) for advanced cancer in man.
The combination of mitomycin C, 5-fluorouracil, and cytosine arabinoside (MFC), which had a marked synergistic effect in the treatment of L1210 mouse leukemia, was used clinically against advanced cancer. Response was assessed according to criteria proposed by Karnofsky. Of 90 patients with various kinds of solid tumors, 17 (19%) had I-B responses and 20 (22%) had I-A responses. Either I-A or I-B responses were observed in 15 (55%) of 27 patients with cancer of the stomach and in nine (60%) of 15 patients with cancer of the colon, indicating that the MFC combination is especially effective against gastrointestinal adenocarcinoma. Bone marrow suppression and gastrointestinal toxicity were observed; however, if the MFC therapy is carried out carefully with adequate intervals between treatments and periodic blood tests, it can be expected to be a safe and useful treatment that is superior to other chemotherapy especially for gastrointestinal cancers.


Patterns of posttraumatic stress symptoms in parents of childhood cancer survivors.
Posttraumatic stress (PTS) symptoms have been reported in mothers and fathers of childhood cancer survivors; however, little is known about patterns of PTS in these families. Cluster analysis was applied to the Posttraumatic Stress Disorder (PTSD) Reaction Index scores of 98 couples parenting adolescent childhood cancer survivors to describe patterns of PTS in families, yielding the following 5 clusters: Minimal PTS, Mothers Elevated, Disengaged, Fathers Elevated, and Elevated PTS. The clusters were validated using data from a structured psychiatric interview, an additional self-report measure of PTS, and an index of family functioning. These clinically meaningful patterns reveal that a majority of families had at least one parent with moderate to severe PTS, which supports development of family-based interventions for this population.


A Multidimensional Approach to Modulating Ionizable Lipids for High-Performing and Organ-Selective mRNA Delivery.
The development of lipid nanoparticles (LNPs) has enabled a successful clinical application of mRNA vaccines. However, disclosure of design principles for the core component-ionizable lipids (ILs), improving the delivery efficacy and organ targeting of LNPs, remains a formidable challenge. Herein, we report a powerful strategy to modulate ILs in one-step chemistry using the Ugi four-component reaction (Ugi-4CR) under mild conditions. A large IL library of new structures was established simply and efficiently through a multidimensional approach, allowing us to identify the top-performing ILs in delivering mRNA via the formulated LNPs. Adjusting the skeleton of ILs has transformed the organ-specific and robust transfection in mRNA delivery from the liver to the spleen following different administration routes. Of note, a series of isomeric ILs were prepared and we found that the isomers mattered greatly in the performance of LNPs for mRNA delivery. Furthermore, owing to the bis-amide bonds formed in the Ugi-4CR reaction, the ILs within LNPs may form hydrogen bonding intermolecularly, facilitating the colloidal stabilization of LNPs. This work provides clues to the rapid discovery and rational design of IL candidates, assisting the application of mRNA therapeutics.


The effects of different endometrial preparation regimens on pregnancy outcomes in frozen-thawed embryo transfer cycles: a prospective randomized controlled study.
An increasing number of research have emerged to compare the pregnancy outcomes between the natural cycle and the hormone replacement therapy (HRT) cycle in preparing the endometrium for frozen-thawed embryo transfer (FET), but the results are controversial. This prospective randomized controlled study was hence designed to obtain more solid evidence. In this study, patients with regular menstrual cycle length (21-35 days) who underwent FET between January 2010 to December 2017 were recruited for this study. Upon further filtering with the selection criteria of patients being, a total of 405 patients were recruited and randomized. Finally, analysis was performed on 384 patients: 178 belonged to the natural cycle group whereas the remaining 206 were in the HRT group. The primary outcome was live birth rate, while the secondary outcomes were implantation rate, clinical pregnancy rate, early miscarriage rate, late miscarriage rate, multiple birth rate and low birth weight rate. The live birth rate (37.6% vs 30.1%, p = 0.119) of natural cycle group were higher than those of the hormone replacement therapy group, although the difference was not significant. The secondary outcomes were not found to differ significantly between the two groups. Nonetheless, the endometrium was found to be thicker in the natural cycle group (10.75 mm) than the HRT group (9.00 mm) (p < 0.001). No significant differences were observed between the pregnancy outcomes of the natural cycle group and the HRT group which comprised of patients with regular menstrual cycle length.


The progression pattern of male hyrax songs and the role of climactic ending.
The study of animal vocal signals can either focus on the properties of distinct vocal elements or address the signal as a whole. Although some attention has been given to the continuous progression patterns of bird songs, such patterns in mammalian vocalisations have been largely overlooked. We examined temporal changes in structural and acoustic parameters in male rock hyrax songs. We found a gradual increase in call frequency and amplitude towards the song ending, as well as an abrupt increase in bout syntactic complexity, peaking in the last quintile of a song. In musical terms, such a pattern can be described as a crescendo (amplitude increase) with a terminal climax. In Western music, crescendos are used to maintain attention and direct the listeners towards a memorable highpoint of the musical piece. This structure may have an analogous function in animal communication, recruiting audience attention towards the climactic and potentially most informative part of the signal. Our playback experiments revealed that hyrax males tend to reply more to songs with a climactic ending, indicating that this progression pattern is important for hyrax communication. We suggest that animal vocal communication research can benefit from adding musical concepts to the analysis toolbox.


Pulmonary involvement in rheumatoid arthritis: multidetector computed tomography findings.
Pulmonary involvement in rheumatoid arthritis (RA) is common and encompasses a large spectrum of disease with different treatment options and prognoses. Therefore, assessment of these patients with multidetector computed tomography (MDCT) is vital. To evaluate the MDCT pulmonary findings of patients with RA and to compare these findings with the clinical status. Chest MDCT scans of 85 patients with RA between 2006-2012 were assessed. One patient with a pulmonary infection was excluded from the study. MDCT findings and distribution of the CT findings were examined, and patients were classified according to the predominant CT pattern. The pulmonary function test (PFT) results and categories, demographic characteristics, and clinical status of some of the patients for whom the results were obtained were evaluated, and the CT findings, PFT results, demographic characteristics, and clinical status were compared. The study group consisted of 20 men (mean age, 58.1 years ± 13.1; range, 15-77 years) and 64 women (mean age, 55.3 years ± 11.5; range, 30-84 years). The most frequent findings were nodules (78.6%) and pleural thickening (48.8%). The most common CT patterns were follicular bronchiolitis (FB) in 28 (33.3%) patients and nodular disease (ND) in 12 (14.3%) others. There was no statistically significant difference between the CT findings and PFT results, and no statistically significant difference was noted in the CT findings between symptomatic and asymptomatic patients. In addition, there were some patients who exhibited no symptoms and/or had abnormal PFT results but had abnormal CT findings. Rheumatoid arthritis is associated with a high frequency of CT findings and CT patterns, with nodules and pleural thickening being the most common CT findings and FB and ND being the most common CT patterns. MDCT identification of patients with RA may be helpful in the evaluation of pulmonary disease, even in patients without symptoms and PFT abnormalities.


Activation in the region of parabrachial nucleus elicits neurogenically mediated coronary vasoconstriction.
A role for parabrachial nucleus in cardiovascular regulation is suggested by evidence that electrical stimulation in this region elicits increase in heart rate and arterial pressure. We hypothesized that parabrachial nucleus may also be involved in control of coronary vasomotor tone. After beta-adrenergic receptor blockade in anesthetized cats, electrical stimulation in the region of parabrachial nucleus produced no change in heart rate, an increase in arterial pressure (34 +/- 6 mmHg), and a transient reduction in coronary blood flow velocity (-21 +/- 2%). Coronary resistance (72 +/- 9%) and femoral resistance (189 +/- 31%) increased markedly. The decrease in coronary blood flow velocity was abolished by stellate ganglionectomy or alpha 1-adrenergic blockade without altering pressor or femoral responses. Injection of the neurotransmitter L-glutamate or kainic acid into parabrachial nucleus also elicited coronary vasoconstriction. We conclude that electrical or chemical activation in the region of parabrachial nucleus elicits coronary vasoconstriction as part of a generalized sympathetic activation. The fact that the coronary response is elicited by chemical activation suggests that cell bodies in the region of medial parabrachial nucleus and subceruleus, as opposed to fibers of passage, are involved in this central neural coronary vasoconstriction.


Effect of organic forms of selenium on delta-aminolevulinate dehydratase from liver, kidney, and brain of adult rats.
The inhibitory effect of various forms of organic selenium compounds and of diphenyl ditelluride (PhTe)2 on delta-aminolevulinate dehydratase (delta-ALA-D) from liver, kidney, and brain of rats was investigated because it has been reported that organocalcogens catalyze the oxidation of thiols. Diphenyl diselenide (PhSe)2, rho-chloro-diphenyl diselenide (rho ClPhSe)2, propyl-2-2-diphenyl diselenide, and propyl-2-methoxy-2-phenyl selenide inhibited delta-ALA-D and the IC50 ranged from 2 to 32 microM depending on the selenium compound and whether it was preincubated with the enzyme. (rho ClPhSe)2 was the most potent inhibitor of delta-ALA-D, and preincubation increased the inhibitory potency of all the tested compounds. Inorganic selenium compounds (sodium selenite, Na2SeO3 and selenium dioxide, SeO2) inhibited delta-ALA-D, and the potency of SeO2 was greater than that of (rho ClPhSe)2. Diphenyl ditelluride (PhTe)2 also inhibited delta-ALA-D but with relatively lower potency than that of organic and inorganic selenium compounds. The inhibitory effect of propyl-2-2-diphenyl diselenide and propyl-2-methoxy-2-phenyl selenide seems to be mediated by (PhSe)2 since the compounds decomposed rapidly to (PhSe)2 in aqueous medium. The inhibitory action of selenium forms on delta-ALA-D from liver, kidney, and brain was antagonized by sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects of organic selenium compounds on delta-ALA-D were related to the stability of the Se-Se (or Se-C) bond because the compound methyl-diphenyl diselenide (which possesses the most stable Se-C-Se bond) did not inhibit the enzyme. The inhibitory action of (PhSe)2 was not related to the formation of oxyradicals in the medium since superoxide dismutase and catalase did not affect the inhibition of delta-ALA-D by (PhSe)2. delta-ALA-D from cucumber leaves was not inhibited by selenium or tellurium compounds which suggests that these compounds act directly on the B or beta-site of the animal enzyme. These results suggest that delta-ALA-D from liver, kidney, and brain is a potential molecular target for the toxic effect of organic forms of selenium and tellurium.


Serum neutrophil gelatinase-associated lipocalin and interleukin-18 as predictive biomarkers for delayed graft function after kidney transplantation.
Early biomarkers for acute kidney injury after kidney transplantation have been studied because delayed graft function (DGF) is associated with increased risk of acute rejection and graft loss. We investigated the usefulness of serum neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) for the prediction of DGF after kidney transplantation. Fifty-nine kidney transplant recipients were included and they were separated into DGF and immediate graft function (IGF) groups. Serum samples were collected on the preoperative day as well as days 1, 5, and 14 after the transplantation, and assayed for NGAL and IL-18. After transplantation, serum levels of NGAL were significantly higher at any time in patients with DGF compared to those with IGF. Serum concentrations of IL-18 were not different between both groups. The receiver operating characteristics(ROC)-area under the curve (AUC) values of NGAL, IL-18, and creatinine on day 1 for the discrimination of DGF from IGF were 0.86, 0.63, and 0.65. On POD1, the sensitivities of NGAL and creatinine were respectively 78.6%, and 50.0% at 77.8% specificity, and the AUC values for any combinations including NGAL and that for NGAL alone were higher than that of creatinine. Serum NGAL is an early and sensitive marker of graft dysfunction in kidney transplantation, while serum IL-18 showed limited values.


Occurrence, Distribution, Evolutionary Relationships, Epidemiology, and Management of Orthotospoviruses in China.
Orthotospoviruses are responsible for serious crop losses worldwide. Orthotospoviral diseases have spread rapidly in China over the past 10 years and are now found in 19 provinces. Currently, 17 Orthotospovirus species have been reported in China, including eight newly identified species from this genus. The number of new highly pathogenic Orthotospovirus strains or species has increased, likely because of the virus species diversity, the wide range of available hosts, adaptation of the viruses to different climates, and multiple transmission routes. This review describes the distribution of Orthotospovirus species, host plants, typical symptoms of infection under natural conditions, the systemic infection of host plants, spatial clustering characteristics of virus particles in host cells, and the orthotospoviral infection cycle in the field. The evolutionary relationships of orthotospoviruses isolated from China and epidemiology are also discussed. In order to effectively manage orthotospoviral disease, future research needs to focus on deciphering the underlying mechanisms of systemic infection, studying complex/mixed infections involving the same or different Orthotospovirus species or other viruses, elucidating orthotospovirus adaptative mechanisms to multiple climate types, breeding virus-resistant plants, identifying new strains and species, developing early monitoring and early warning systems for plant infection, and studying infection transmission routes.


Toxic effect of single and binary treatments of synthetic and plant-derived molluscicides against Achatina fulica.
The toxic effect of single and binary treatments of synthetic and plant-derived molluscicides was studied against the harmful terrestrial snail Achatina fulica. In single treatments, among the synthetic molluscicides Snail Kill and cypermethrin were potent, whereas Cedrus deodara oil was more toxic among molluscicides of plant origin against A. fulica. In binary treatments, a combination of Cedrusdeodara + Alliumsativum was more toxic. The toxicities of these single and binary treatments of synthetic and plant-derived molluscicides were dose and time dependent.


[Neurological disorders in liver transplantation].
Liver transplantation is the only curative treatment in patients with end-stage liver failure. It has been associated with neurological disorders more frequently than other solid organ transplantations. We aimed to detect neurological disorders in liver transplantation patients and determine those that affect mortality. One hundred eighty-five patients, 105 with and 80 without neurological disorders, were included in this study. The follow-up was categorized into three periods: preoperative, early postoperative and late postoperative. We analyzed all medical records, including demographic, laboratory, radiological, and clinical data. Neurological disorders were observed in 52 (28.1%) patients in the preoperative period, in 45 (24.3%) in the early postoperative, and in 42 (22.7%) in the late postoperative period. Hepatic encephalopathy in the preoperative and altered mental state in the post-operative period were the most common neurological disorders. Both hepatic encephalopathy (37.5%) and altered mental state (57.7%) caused high mortality (p=0.019 and 0.001) and were determined as indepen-dent risk factors for mortality. Living donor transplantation caused less frequent mental deterioration (p=0.049). The mortality rate (53.8%) was high in patients with seizures (p=0.019). While mortality was 28.6% in Wilson's disease patients with neurological disorders, no death was observed in patients without neurological disorders. We identified a wide variety of neurological disorders in liver transplantation patients. We also demonstrated that serious neurological disorders, including hepatic encephalopathy and seizures, are associated with high morbidity and mortality. Therefore, in order to avoid poor outcomes, hepatic encephalopathy should be considered as a prioritization criterion for liver transplantation.


Impact of the route of clean intermittent catheterization on quality of life in children with lower urinary tract dysfunction.
To compare the impact of the different routes for clean intermittent catheterization on the quality of life of children with lower urinary tract dysfunction. In this cross-sectional study, all children and adolescents under treatment in our clinic from August 2011 to May 2012 who were on CIC for bladder dysfunction were included. To evaluate the technical difficulty and the discomfort associated with the procedure we used a standard visual analog scale. Quality of life was measured using the Pediatric Quality of Life Inventory Version 4.0. A total of 70 children including 38 (54.3%) boys and 32 (45.7%) girls with a mean age of 11.8 ± 3.6 years (range 5 to 18 years) were evaluated. The mean daily number of catheterizations was 4.2 ± 1.1. CIC was performed through the urethra in 51 (72.9%) subjects and a stoma in 19 (27.1%). A 45 (64.3%) were assisted by a caregiver to perform a catheterization. No differences in both difficulty and discomfort for performing CIC were observed between groups. Children who performed CIC through a stoma had a better quality of life scores for the physical (P = 0.015) and social functioning domains (P = 0.011). The quality of life of children and adolescents performing CIC appears to be affected by the route of catheterization, with a worse performance for those using urethral catheterization.


[Splenic involvement in infectious endocarditis. 5 clinical cases and 78 necropsies].
Splenic involvement is a classical complication of infective endocarditis (IE). Clinical manifestations are rare, 5 out of 100 IE: unexpected rupture (1 case), abscess causing reinfection (2 cases), pseudo-tumour (1 case) and terminal infarction (1 case). In addition to a review of the literature, a post mortem histological study of the spleen of 78 cases of IE was undertaken. Splenic involvement did not seem to be the direct cause of death. Three types of lesions which may or may not be associated were observed: congestive inflammatory lesions, infarction (48 p. 100), abscess (6 p. 100). Splenic infarction usually results in scarring but may progress to abscess formation. Rupture was not observed in this autopsy series. Although splenic involvement is common at post mortem it gives rise to few symptoms. Persistant pyrexia and the appearance of local signs should lead to investigation of splenic complications and eventually, to surgical ablation.


Aotus New World monkeys: model for studying malaria-induced anemia.
Falciparum malaria is a major cause of disease and death in African children and pregnant women, primarily due to severe anemia. We studied anemia in vaccinated Aotus monkeys during a second infection where the animals were considered to be semi-immune. Most animals had extremely low or undetectable levels of parasitemia; in some, anemia did not develop and reticulocytemia remained unchanged; in others, moderate to severe anemia developed with inappropriately low reticulocytemia indicating bone marrow dysfunction. Bone marrow rapidly responded after parasite clearance. The rapid drop in hematocrit despite extremely low to undetectable parasitemia indicated massive removal of uninfected red blood cells from the circulation that, in the presence of bone marrow dysfunction, led to severe anemia-the problem that occurs in African children. We demonstrate that Aotus monkeys are a nonhuman primate model to gain insight into the pathogenesis of severe anemia in African children.


Prediction of Synergistic Antibiotic Combinations by Graph Learning.
Antibiotic resistance is a major public health concern. Antibiotic combinations, offering better efficacy at lower doses, are a useful way to handle this problem. However, it is difficult for us to find effective antibiotic combinations in the vast chemical space. Herein, we propose a graph learning framework to predict synergistic antibiotic combinations. In this model, a network proximity method combined with network propagation was used to quantify the relationships of drug pairs, and we found that synergistic antibiotic combinations tend to have smaller network proximity. Therefore, network proximity can be used for building an affinity matrix. Subsequently, the affinity matrix was fed into a graph regularization model to predict potential synergistic antibiotic combinations. Compared with existing methods, our model shows a better performance in the prediction of synergistic antibiotic combinations and interpretability.


Self-Cleaning Membranes from Comb-Shaped Copolymers with Photoresponsive Side Groups.
In this study, we present a novel self-cleaning, photoresponsive membrane that is capable of removing predeposited foulant layers upon changes in surface morphology in response to UV or visible light irradiation while maintaining stable pore size and water permeance. These membranes were prepared by creating thin film composite (TFC) membranes by coating a porous support membrane with a thin layer of novel comb-shaped graft copolymers at two side-chain lengths featuring polyacrylonitrile (PAN) backbones and photoreactive side chains, synthesized by atom transfer radical polymerization (ATRP). Photoregulated control over membrane properties is attained through a light-induced transition, where the side chains switch between a hydrophobic spiropyran (SP) state and a zwitterionic, hydrophilic merocyanine (MC) state. The light-induced switch between the SP and MC forms changes surface hydrophilicity and causes morphological changes on the membrane surface as evidenced by atomic force microscopy (AFM). Before any phototreatment, the as-coated membrane surface comprises mostly hydrophobic SP groups that allow the adsorption of organic solutes such as proteins the membrane surface, reducing flow rate. Once exposed to UV light, conversion of the SP groups to hydrophilic MC groups leads to the release of adsorbed molecules and the full recovery of the initial water flux. A fouled membrane in the more hydrophilic MC form is also capable of self-cleaning upon conversion to the less hydrophilic SP form by visible light irradiation. The self-cleaning behavior observed for this system, where the surface became less hydrophilic but also experienced a morphological change, demonstrates a novel mechanism that has a mechanical component in addition to the changes in hydrophilicity. It is also the first report, to our knowledge, of self-cleaning performance accompanied by a decrease in hydrophilicity.


Unusual presentation of multiple myeloma. A report of 2 cases.
The diagnosis of multiple myeloma (overt plasma cell dyscrasia) is usually not considered in patients under 30 years of age. Furthermore, multiple myeloma with coexistent megaloblastic and iron deficiency anaemia is very uncommon. Within 6 months we encountered 2 patients under 30 years of age who had multiple myeloma, one with advanced secondary amyloidosis and the other with severe megaloblastic and iron deficiency anaemia.


Dimethylzinc-mediated, enantioselective synthesis of propargylic amines.
A one-pot, enantioselective synthesis of N-aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o-methoxyaniline as starting materials, has been developed. Enantiopure beta-amino alcohols derived from norephedrine were used as non-covalent chiral auxiliaries, both in stoichiometric or substoichiometric amount. After optimization, propargylic amines were obtained in good to high yields (up to 93%) and with moderate to high enantiomeric excesses (up to 97% ee). The possibility to recover the chiral auxiliary after the reaction was demonstrated.


Bilateral Distraction Osteogenesis of Vascularized Iliac Crest Free Flaps Used in Mandibular Reconstruction.
Vascularized free flaps have become the gold standard in reconstructing large segmental mandibular defects; however, even when bony union and soft-tissue coverage is achieved, insufficient bone stock and altered facial contour can create functional and cosmetic problems for the patient. There have been limited case reports on the use of secondary distraction osteogenesis to address these issues. The authors report a case of bilateral mandibular distraction of deep circumflex iliac artery free flaps, used for mandibular reconstruction after total mandibulectomy for treatment of osteosarcoma. Performed for reasons of retrognathia and facilitation of dental prosthetic rehabilitation, this is the first case of bilateral horizontal distraction osteogenesis of deep circumflex iliac artery free flaps reported in the literature.


A magnetic bottle time-of-flight electron spectrometer suitable for continuous ionization sources.
We present a newly developed magnetic-bottle time-of-flight electron spectrometer suitable for continuous or quasicontinuous photoionization sources such as synchrotrons. A strong magnetic field collects almost all photoelectrons from a well-defined ionization volume and quantitatively suppresses background electrons which originate outside of this interaction region. Although it is a pulsed instrument, a relatively high duty cycle is achieved by storing the photoelectrons generated between two cycles in an electromagnetic trap. This makes the new instrument suitable for experiments with very low sample densities. Another advantage is the high energy resolution, 50 meV in the first version of the spectrometer described here, which simply depends on the length of the time-of-flight instrument.


The association of atrial tachyarrhythmias with isolated atrial amyloid disease: preliminary observations in autopsied heart specimens.
Isolated atrial amyloidosis (IAA) is associated with atrial tachyarrhythmias. However, only a few studies have appraised atrial tachyarrhythmias and atrial depolarization abnormalities in connection with high-grade IAA. We conducted a collaborative retrospective study to assess this association. One hundred consecutive autopsied hearts were studied histologically for IAA. To increase the specificity for atrial depolarization abnormalities in this preliminary study, we excluded those specimens with intermediate amyloid involvement, i.e. IAA grades 1 and 2 (grade 0 = absent or trivial deposits; grade 1 = small deposits; grade 2 = moderate deposits; grade 3 = dense, large deposits). We then screened for baseline, premortem electrocardiograms (ECGs) to assess rhythm. In those with sinus rhythm, the P wave axis, duration, dispersion and terminal force in V1 were determined under magnification. Of the 27 premortem ECGs corresponding to the autopsy specimens with grades 3 (sample) or 0 (controls) IAA, 9 showed sinus rhythm, 13 showed atrial fibrillation, 1 showed atrial flutter and 4 were uninterpretable. Fourteen autopsied hearts (52%) were positive for grade 3 IAA. Ten of those had atrial tachyarrhythmias (9 atrial fibrillation and 1 atrial flutter) compared to 4 of the 13 hearts with grade 0 IAA (72 vs. 31%, respectively; p = 0.03). Although there was excellent interobserver agreement using intraclass correlation coefficients, there were no significant differences in P wave measurements among the small number of patients with sinus rhythm for grade 3 versus grade 0 IAA. In a collaborative, preliminary, pilot assessment of autopsied hearts for which premortem ECGs were necessarily screened retrospectively, significantly more hearts with high-grade IAA were associated with atrial tachyarrhythmias compared to those with low-grade IAA. A larger study with an appropriately matched autopsy control group is needed to confirm these and previous observations.


Natural infections of Crenosoma vulpis and Angiostrongylus vasorum in dogs in Atlantic Canada and their treatment with milbemycin oxime.
Milbemycin oxime was used to treat dogs with natural infections of the fox lungworm, Crenosoma vulpis and the French heartworm, Angiostrongylus vasorum. Crenosomosis was identified in 42 of 202 dogs with clinical signs of coughing, dyspnoea or exercise intolerance by a Baermann analysis of faecal samples taken between October 2000 and October 2001. It occurred throughout Atlantic Canada (New Brunswick, Newfoundland, Nova Scotia and Prince Edward Island). The clinical signs resolved and shedding of larvae in faeces ceased in all 32 Crenosoma-infected dogs given a single oral dose of 0.5 mg/kg milbemycin oxime for which the results of faecal examinations were available. Angiostrongylosis was identified in 16 of the 202 dogs and was restricted to the Avalon peninsula of Newfoundland, where 67 dogs were tested. The clinical signs resolved and shedding of larvae ceased in 14 of the 16 dogs treated with four, weekly oral doses of 0.5 mg/kg milbemycin oxime. One dog with severe clinical signs died during the course of treatment and one owner failed to provide a faecal sample from their dog but reported that the clinical signs had resolved.


Tests for homogeneity of the risk difference when data are sparse.
Test statistics for the homogeneity of the risk difference for a series of 2 x 2 tables when the data are sparse is proposed. A weighted least squares statistic is commonly used to test for equality of the risk difference over the tables; however, when the data are sparse, this statistic can have anticonservative Type I error rates. Simulation is used to compare the proposed test statistics to the weighted least squares statistic. The weighted least squares statistic has the most anticonservative Type I error rates of all the statistics compared. We suggest the use of one of our proposed test statistics instead of the weighted least squares statistic.


Possible Risk Factors for Acute Stress Disorder and Post-Traumatic Stress Disorder After an Industrial Explosion.
There have been deaths and injuries after an explosion which happened in an industrial region in Ankara in February 2011. The aim of this study was to determine the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD), and to determine the variables which can be the risk factors for PTSD. In this study, we included a total of 197 subjects who were present at the factory building and at the four offices nearby when the disaster occurred. All the participants were assessed one month after the explosion and 157 of them were reassessed six months after the explosion. Socio-demographic information forms were given and the Clinician-Administered PTSD Scale (CAPS) was administered to the participants one month after the explosion. Psychiatric assessments were done using the structured clinical interview for DSM-IV axis-I disorders (SCID-I). The CAPS was re-applied six month after the disaster. At the first-month assessments, ASD was detected in 37.1% of participants and PTSD in 13.7%, whereas PTSD was observed in 16.6% of subjects at the sixth month of the accident. According to the first month data, having any psychiatric disorder before the incident, physical injury, acquaintances among the dead and the injured people, being involved in the incident and seeing dead people were detected as the risk factors for PTSD. At the sixth month assessment, physical injury, acquaintances among the dead and the injured, being involved in the incident were seen as risk factors for PTSD. ASD and PTSD can be seen after an explosion. Having a previous psychiatric disorder and being directly affected by trauma and being injured are the risk factors for PTSD. This study implies that preventive mental health care services should include the management of current psychiatric condition and employee safety issues.


Treatment of seropositive primary syphilis: an evaluation of 196 patients.
One hundred seventy-five patients with primary infection with Treponema pallidum were treated with benzathine penicillin G, 2.4 million units given intramuscularly weekly for two weeks for a total of 4.8 million units. Twenty-one patients with primary syphilis who were allergic to penicillin were treated with oral tetracycline, 500 mg four times daily for 12 days for a total of 24 gm. All 196 patients had resolution of their lesions, and all were seronegative within one year. White patients presented for treatment earlier than black patients. The duration of symptoms prior to presentation for treatment was positively correlated with the height of the serologic titer in the rapid plasma reagin card test. Patients who had high titers before treatment became seronegative less rapidly than patients who had low pretreatment titers.


Chronic unpredictable stress induces anxiety-like behaviors in young zebrafish.
Exposure to stress during early life affects subsequent behaviors and increases the vulnerability to adult pathologies, a phenomenon that has been well documented in humans and rodents. In this study, we introduce a chronic unpredictable stress protocol adapted to young zebrafish, which is an increasingly popular vertebrate model in neuroscience research. We exposed zebrafish to a series of intermittent and unpredictable mild stressors from day 10 to 17 post-fertilization. The stressed fish showed a reduced exploration of a novel environment one day post-stress and an increased responsiveness to dark-light transition two days post-stress, indicative of heightened anxiety-related behaviors. The stress-induced decrease in exploration lasted for at least three days and returned to control levels within one week. Moreover, stressed fish were on average 8% smaller than their control siblings two days post-stress and returned to control levels within one week. All together, our results demonstrate that young zebrafish exposed to chronic unpredictable stress develop growth and behavioral alterations akin to those observed in rodent models.


Resting heart rate is associated with colorectal advanced adenoma.
Resting heart rate is an independent predictor of colorectal cancer (CRC) development and CRC-related mortality. However, little is known about the relationship between resting heart rate and colorectal adenoma development. We aimed to investigate this association in a population who underwent screening colonoscopy. Among 39,021 patients who underwent both electrocardiogram and screening colonoscopy during routine health examinations at the Seoul National University Bundang Hospital, Health Promotion Center, Korea from January 2014 to July 2019, 1,344 patients had advanced adenoma. We performed 1:1 propensity score (PS) matching to establish a control group that mitigated the confounding effects of age and sex. We performed multivariate logistic regression analyses to identify the independent risk factors of advanced adenoma development. Resting heart rate was significantly higher in the advanced adenoma group than in the control group. The prevalence of advanced polyp increased across the quartiles of resting heart rate. Patients with higher resting heart rates were more likely to be older, smokers, and have increased blood pressure and DM and less likely to engage in active exercises than those with lower resting heart rates. Patients with higher resting heart rates had higher serum glucose, triglyceride, hemoglobin A1C, and insulin levels and lower high-density lipoprotein cholesterol levels. Patients with resting heart rate in the highest quartile (≥71 bpm) still showed significantly increased odds ratio (OR) of advanced adenoma development (OR: 1.379, 95% confidence interval: 1.099-1.731, p = 0.006). High resting heart rate was a meaningful independent risk factor of advanced adenoma development.


Virulence Gene Regulation in Escherichia coli.
Escherichia colicauses three types of illnesses in humans: diarrhea, urinary tract infections, and meningitis in newborns. The acquisition of virulence-associated genes and the ability to properly regulate these, often horizontally transferred, loci distinguishes pathogens from the normally harmless commensal E. coli found within the human intestine. This review addresses our current understanding of virulence gene regulation in several important diarrhea-causing pathotypes, including enteropathogenic, enterohemorrhagic,enterotoxigenic, and enteroaggregativeE. coli-EPEC, EHEC, ETEC and EAEC, respectively. The intensely studied regulatory circuitry controlling virulence of uropathogenicE. coli, or UPEC, is also reviewed, as is that of MNEC, a common cause of meningitis in neonates. Specific topics covered include the regulation of initial attachment events necessary for infection, environmental cues affecting virulence gene expression, control of attaching and effacing lesionformation, and control of effector molecule expression and secretion via the type III secretion systems by EPEC and EHEC. How phage control virulence and the expression of the Stx toxins of EHEC, phase variation, quorum sensing, and posttranscriptional regulation of virulence determinants are also addressed. A number of important virulence regulators are described, including the AraC-like molecules PerA of EPEC, CfaR and Rns of ETEC, and AggR of EAEC;the Ler protein of EPEC and EHEC;RfaH of UPEC;and the H-NS molecule that acts to silence gene expression. The regulatory circuitry controlling virulence of these greatly varied E. colipathotypes is complex, but common themes offerinsight into the signals and regulators necessary forE. coli disease progression.


[Chemico-enzymatic synthesis of branched O-specific polysaccharides of Salmonella serotype C2 and C3].
The possibility of chemical-enzymatic synthesis of branched polysaccharides was demonstrated with the enzymes from Salmonella newport and S. kentucky using synthetic polyprenyl pyrophosphate oligosaccharides. Formation of polymers with alpha 1-2-, beta 1-2-alpha 1-4- and beta 1-4-linkages between glucose residues in the branch and galactose residues of the main chain was shown.


Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors.
Recent studies in Drosophila melanogaster retina indicate that absorption of light causes the translocation of signaling molecules and actin from the photoreceptor's signaling membrane to the cytosol, but the underlying mechanisms are not fully understood. As ezrin-radixin-moesin (ERM) proteins are known to regulate actin-membrane interactions in a signal-dependent manner, we analyzed the role of Dmoesin, the unique D. melanogaster ERM, in response to light. We report that the illumination of dark-raised flies triggers the dissociation of Dmoesin from the light-sensitive transient receptor potential (TRP) and TRP-like channels, followed by the migration of Dmoesin from the membrane to the cytoplasm. Furthermore, we show that light-activated migration of Dmoesin results from the dephosphorylation of a conserved threonine in Dmoesin. The expression of a Dmoesin mutant form that impairs this phosphorylation inhibits Dmoesin movement and leads to light-induced retinal degeneration. Thus, our data strongly suggest that the light- and phosphorylation-dependent dynamic association of Dmoesin to membrane channels is involved in maintenance of the photoreceptor cells.


Inhibition of platelet thromboxane synthetase by 1-(3-benzyloxy-1[E]octenyl)imidazole.
1-(3-Benzyloxy-1[E]octenyl)imidazole (CBS-645) is a specific inhibitor of thromboxane synthetase. It inhibits the platelet enzyme in human and rabbit at micromolar concentrations. At a dose of 12.5 mg kg-1 in rabbits, CBS-645 displays a prolonged inhibitory effect on the formation of thromboxane (Tx) B2 induced by blood coagulation in vitro. In human volunteers, an oral dose of 50 mg leads to an average 70% inhibition of TxB2 formation. CBS-645 administered at a dose of 25 mg kg-1 p.o. in the rat, significantly increases bleeding time. In another test in which platelet interaction with the vessel wall is involved, i.e. in vivo platelet deposition onto desendothelialized aorta in the rabbit, the drug shows antithrombotic activity after a single oral administration of 5 mg kg-1. CBS-645 could be of interest in the treatment of the various diseases in which the pathological role of thromboxane A2 is suspected.


The influence of EEG channels and features significance on automatic detection of epileptic waves in MECT.
Modified Electric Convulsive Therapy (MECT) is an efficacious physical therapy in treating mental disorders. The occurrence of epilepsy is a crucial benchmark for evaluating therapeutic effectiveness. However, the medical field still lacks relevant research on automatically detecting epileptic waves in MECT. Therefore, this article proposes a novel automatic detection method of epileptic waves in MECT. In this article, EEG local features (time, frequency, and time-frequency domains) and global features (Pearson correlation coefficient) are combined for epileptic wave detection with SVM (Support Vector Machine). We researched the system with 15 EEG detection channels. The dataset under investigation contains EEG data from 22 patients who received MECT and presented with epileptic seizures. The results revealed that LA (Logarithm of Activity) feature exhibits the best classification significance. When epileptic waves appear, there is a decrease in the power ratio of delta waves and an increase in the power ratio of theta waves. Additionally, the complexity of EEG decreases while the correlation between EEG channels increases. The Cz, F4, and P3 channels exhibit the highest classification significance among all EEG channels. Furthermore, based on the channel classification significance, the EEG detection channels number can be reduced to 8. Similarly, based on the feature classification significance, the local feature number can be reduced from 9 to 3. These conclusions can improve detection efficiency and reduce the cost for MECT. Moreover, the method we proposed can effectively detect epileptic waves in MECT. This work can provide physicians with a reference for evaluating the effectiveness of MECT.


Rosacea in skin of color: not a rare diagnosis.
The prevalence of rosacea in skin of color is not well characterized and may be underestimated. Physicians may not recognize and diagnose rosacea correctly in skin of color. To assess the prevalence of rosacea in skin of color and determine if patients of color with rosacea symptoms are receiving a diagnosis of rosaceaMethods: We analyzed the National Ambulatory Medical Care Survey (NAMCS) for 1993-2010 for racial and ethnic distribution of patients with rosacea. Common reasons for visit in rosacea patients were tabulated and frequency of rosacea diagnosis was compared in patients of each race with the relevant reasons for visit. Of all patients diagnosed with rosacea, 2.0% were black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino of any race. Leading reasons for visit associated with rosacea included "other diseases of the skin", skin rash, and discoloration or abnormal pigmentation. Rosacea was the primary diagnosis for 8.3% of whites and 2.2% of blacks complaining of "other diseases of the skin", for 2.0% of whites and 0.6% of blacks complaining of skin rash, and for 3.0% of whites and 0.0% of blacks complaining of discoloration or abnormal pigmentation. The percentage of rosacea patients who were black or Asian/Pacific Islander did not change significantly over time. No specific reason-for-visit code indicating rosacea exists in the NAMCS. Prevalence may be underestimated if some patients do not visit a physician for treatment. Patients of color rarely receive a diagnosis of rosacea, even when they have symptoms suggesting it. Rosacea has not become more commonly diagnosed in skin of color in recent years.


Septicemia secondary to ileus in trauma patients: a human model for bacterial translocation.
Paralytic ileus is a common problem in trauma patients. We present two cases of ileus leading to septicemia. Both patients developed sudden septicemia on hospital day six and underwent urgent exploratory laparotomies, and both were found to only have paralytic ileus without evidence of bowel injury or obstruction. We attribute the cause of septicemia to bacterial translocation secondary to ileus.


[Study on the health effect of the occupational stress in aircrew].
Objective: To explore the relationship between occupational stress and physiological and biochemical indexes, to research the health effect of the occupational stress in aircrew. Methods: 450 aircrews were conducted with the OSI-R questionnaire survey, examine the level of blood pressure, blood routine, ALT and UA. Results: The concentration of HB was positively related with task conflict and entertainment and leisure (β=0.262 and 0.106, both P<0.05) , while heavy task, task discomfort and psychological stress reactions were negatively related with HB (β=-0.163, -0.102, and -0.137, all P<0.05) ; task conflict and self-care were positively related with RBC (β=0.221 and 0.159, both P<0.01) , heavy task, psychological stress reactions and social support were negatively related with RBC (β=-0.157, -0.119, and -0.113, all P<0.05) ; task ambiguity and self-care had a positive relationship with ALT (β=0.144 and 0.159, both P<0.01) while heavy task, psychological stress reactions and social support had a negative relationship with ALT (β=-0.176, -0.096, and -0.102, all P<0.05) ; self-care was positively related with SBP (β=0.170, P<0.01) , task discomfort, interpersonal stress reactions and social support were negatively related with SBP (β=-0.093, -0.103, and -0.111, all P<0.05) ; while self-care was positively related with DBP (β=0.139, P<0.01) , social support was negatively related with DBP (β=-0.114, P<0.05) . Conclusion: Occupational stress of the aircrew is significantly related with blood pressure, RBC, ALT and UA, occupational stress can make effects on the health of aircrew.


Diabetes and COVID-19: Population Impact 18 Months Into the Pandemic.
Eighteen months into the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic, epidemiologic studies indicate that diabetes is a central contributor to severe COVID-19 morbidity, and, conversely, COVID-19 has had a devastating effect on the population with diabetes. In this literature synthesis, we summarize the relationship of diabetes to COVID-19-related morbidity and mortality, discuss the predictors of severe adverse outcomes and implications of the overall pandemic, and critique the current status of and identify needs for epidemiologic studies for the next phase of the pandemic. Case series show that ∼30-40% of people with COVID-19-related hospitalization, severe morbidity requiring intensive care, and/or death have type 2 or type 1 diabetes. Among hospitalized individuals with diabetes, ∼21-43% required intensive care and case fatality is ∼25%. Risk of severe morbidity and mortality is 100-250% higher among people with diabetes than those without, even after adjustment for sociodemographic factors and comorbid conditions. Impact on the general population with diabetes has been similarly dire, as overall mortality rates were 50% higher than historical trends, a net increase more than twice that of the general population. Of the excess deaths, ∼75-80% are not officially attributed to COVID-19, which raises unanswered questions about missed attribution or collateral impact. Many predictors of poor outcomes have been identified, particularly comorbid conditions (chronic kidney disease, coronary heart disease, and heart failure), concurrent obesity, and acute and chronic poor HbA1c control, that point to the potential to reduce severe morbidity and mortality in its next stages. However, response to the continuing pandemic will benefit from population-wide studies with broader examination of the risks of exposure, infection, and hospitalization, for which few data currently exist. The indirect impact of the pandemic's effects on health services, health behaviors, disease management, care, control, and complications has not been well quantified; determining this impact will be essential to lessen the future impact. Expanding epidemiologic studies of the relationship of diabetes to COVID-19 beyond few high-income countries will also be essential to limit the burden in low- and middle-income countries where 80% of individuals with diabetes reside and where the COVID-19 pandemic has been so damaging.


DNA HETEROZYGOSITY AND GROWTH RATE IN THE ATLANTIC COD GADUS MORHUA (L).
Relationships between growth rate and the degree of individual heterozygosity at ten nuclear RFLP loci were examined in two populations of the Atlantic cod, Gadus morhua, from northern Norway. A highly significant positive correlation was observed between growth rate and DNA heterozygosity in one population (Balsfjord) but not in the other (Barents Sea). Our results provide support for an important prediction of the associative overdominance hypothesis that heterozygosity-fitness correlations can be detected at neutral genetic markers and suggest that environmental conditions might play a dominant role in the manifestation of the correlation.


Utility of a Smartphone-Based System (cvrPhone) in Estimating Minute Ventilation from Electrocardiographic Signals.
Background: We investigated the ability of a novel stand-alone, smartphone-based system, the cvrPhone, in estimating the minute ventilation (MV) from body surface electrocardiographic (ECG) signals. Methods: Twelve lead ECG signals were collected from anesthetized and mechanically ventilated swine (n = 9) using standard surface electrodes and the cvrPhone. The tidal volume delivered to the animals was varied between 0, 250, 500, and 750 mL at respiration rates of 6 and 14 breaths/min. MV estimates were determined by the cvrPhone and were compared with the delivered ones. Results: The median relative estimation errors were 17%, -4%, 35%, -3%, -9%, and 1%, for true MVs of 1,500, 3,000, 3,500, 4,500, 7,000, and 10,500 breaths*mL/min, respectively. The MV estimates at each of the settings were significantly different from each other (p < 0.05). Conclusions: We have demonstrated that accurate MV estimations can be derived from standard body surface ECG signals, using a smartphone.


Palliative care: what is it?
Palliative care developed during the hospice movement. Hospice was associated as a rest place for weary travelers in ancient times, many of whom were ill. Hospice first became associated with the dying in France in 1842; the first modern hospice, St. Christopher's Hospice, was established in London by Dame Cicely Saunders in 1967. It was the first facility founded as a "place" to care for the dying. In 1974, the first U.S. hospice was established in Connecticut based on a home care model. In 1975, Balfour Mount, MD, founded the Palliative Care Service in The Royal Victoria Hospital in Montreal; the concept of "palliative care" in North America was established (Sheehan & Forman, 1996). The traditional view of palliative care indicates that symptomatic and supportive care are generally withheld until all attempts to treat the underlying disease and other medical problems are exhausted. Many times, palliative care is offered with little time left for living. Palliative care should be considered in conjunction with active treatment, and, as death nears, palliative care becomes more important as active treatment while cure become less important.