Lipid Droplets in Neurodegenerative Disorders.
Knowledge of lipid droplets (LDs) has evolved from simple depots of lipid storage to dynamic and functionally active organelles involved in a variety of cellular functions. Studies have now informed significant roles for LDs in cellular signaling, metabolic disease, and inflammation. While lipid droplet biology has been well explored in peripheral organs such as the liver and heart, LDs within the brain are relatively understudied. The presence and function of these dynamic organelles in the central nervous system has recently gained attention, especially in the context of neurodegeneration. In this review, we summarize the current understanding of LDs within the brain, with an emphasis on their relevance in neurodegenerative diseases.


Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.
To evaluate a clinical guideline for the treatment of ventilator-associated pneumonia. Prospective before-and-after study design. A medical intensive care unit from a university-affiliated, urban teaching hospital. Between April 1999 and January 2000, 102 patients were prospectively evaluated. Prospective patient surveillance, data collection, and implementation of an antimicrobial guideline for the treatment of ventilator-associated pneumonia. The main outcome evaluated was the initial administration of adequate antimicrobial treatment as determined by respiratory tract cultures. Secondary outcomes evaluated included the duration of antimicrobial treatment for ventilator-associated pneumonia, hospital mortality, intensive care unit and hospital lengths of stay, and the occurrence of a second episode of ventilator-associated pneumonia. Fifty consecutive patients with ventilator-associated pneumonia were evaluated in the before period and 52 consecutive patients with ventilator-associated pneumonia were evaluated in the after period. Severity of illness using Acute Physiology and Chronic Health Evaluation II (25.8 +/- 5.7 vs. 25.4 +/- 8.1, p =.798) and the clinical pulmonary infection scores (6.6 +/- 1.0 vs. 6.9 +/- 1.2, p =.105) were similar for patients during the two treatment periods. The initial administration of adequate antimicrobial treatment was statistically greater during the after period compared with the before period (94.2% vs. 48.0%, p <.001). The duration of antimicrobial treatment was statistically shorter during the after period compared with the before period (8.6 +/- 5.1 days vs. 14.8 +/- 8.1 days, p <.001). A second episode of ventilator-associated pneumonia occurred statistically less often among patients in the after period (7.7% vs. 24.0%, p =.030). The application of a clinical guideline for the treatment of ventilator-associated pneumonia can increase the initial administration of adequate antimicrobial treatment and decrease the overall duration of antibiotic treatment. These findings suggest that similar types of guidelines employing local microbiological data can be used to improve overall antibiotic utilization for the treatment of ventilator-associated pneumonia.


Clinical Evaluation of NIKS-Based Bioengineered Skin Substitute Tissue in Complex Skin Defects: Phase I/IIa Clinical Trial Results.
Complex skin defects, such as burns and acute cutaneous trauma, are life-threatening injuries, often requiring temporary allograft placement to maintain fluid homeostasis and prevent infection until permanent wound closure is possible. The current standard of care for the management of full-thickness wounds that are unable to be closed in a single surgical stage is temporary coverage with cadaver allograft until an acceptable wound bed has been established. This approach has limitations including limited availability of human cadaver skin, the risk of disease transmission from cadaveric grafts, and inconsistent cadaver allograft quality. Near-diploid neonatal human keratinocyte cell line (NIKS)-based human skin tissue is a full-thickness, living human skin substitute composed of a dermal analog containing normal human dermal fibroblasts and a fully-stratified, biologically and metabolically active epidermis generated from NIKS keratinocytes, a consistent and unlimited source of pathogen-free human epidermal progenitor cells. NIKS-based human skin tissue is a living bioengineered skin substitute (BSS) intended to provide immediate wound coverage and promote wound healing through sustained expression by living cells of wound healing factors. A phase I/IIa clinical trial found that NIKS-based BSS was well tolerated and comparable to cadaver allograft in the ability to prepare full-thickness complex skin defects prior to autografting. There were no deaths and no adverse events (AE) associated with this BSS. Exposure of the study subjects to the skin substitute tissue did not elicit detectable immune responses. Notably, this tissue remained viable and adherent in the wound bed for at least 7 days.


Heterologous Expression and Biochemical Characterization of Two Lipoxygenases in Oriental Melon, Cucumis melo var. makuwa Makino.
Lipoxygenases (LOXs) are a class of non-heme iron-containing dioxygenases that catalyse oxidation of polyunsaturated fatty acids to produce hydroperoxidation that are in turn converted to oxylipins. Although multiple isoforms of LOXs have been detected in several plants, LOXs in oriental melon have not attracted much attention. Two full-length LOX cDNA clones, CmLOX10 and CmLOX13 which have been isolated from oriental melon (Cucumis melo var. makuwa Makino) cultivar "Yumeiren", encode 902 and 906 amino acids, respectively. Bioinformatics analysis showed that CmLOX10 and CmLOX13 included all of the typical LOX domains and shared 58.11% identity at the amino acid level with each other. The phylogenetic analysis revealed that CmLOX10 and CmLOX13 were members of the type 2 13-LOX subgroup which are known to be involved in biotic and abiotic stress. Heterologous expression of the full-length CmLOX10 and truncated CmLOX13 in Escherichia coli revealed that the encoded exogenous proteins were identical to the predicted molecular weights and possessed the lipoxygenase activities. The purified CmLOX10 and CmLOX13 recombinant enzymes exhibited maximum activity at different temperature and pH and both had higher affinity for linoleic acid than linolenic acid. Chromatogram analysis of reaction products from the CmLOX10 and CmLOX13 enzyme reaction revealed that both enzymes produced 13S-hydroperoxides when linoleic acid was used as substrate. Furthermore, the subcellular localization analysis by transient expression of the two LOX fusion proteins in tobacco leaves showed that CmLOX10 and CmLOX13 proteins were located in plasma membrane and chloroplasts respectively. We propose that the two lipoxygenases may play different functions in oriental melon during plant growth and development.


Highly variable spike trains underlie reproducible sensorimotor responses in the medicinal leech.
The nervous system of the leech is a particularly suitable model to investigate neural coding of sensorimotor responses because it allows both observation of behavior and the simultaneous measurement of a large fraction of its underlying neuronal activity. In this study, we used a combination of multielectrode recordings, videomicroscopy, and computation of the optical flow to investigate the reproducibility of the motor response caused by local mechanical stimulation of the leech skin. We analyzed variability at different levels of processing: mechanosensory neurons, motoneurons, muscle activation, and behavior. Spike trains in mechanosensory neurons were very reproducible, unlike those in motoneurons. The motor response, however, was reproducible because of two distinct biophysical mechanisms. First, leech muscles contract slowly and therefore are poorly sensitive to the jitter of motoneuron spikes. Second, the motor response results from the coactivation of a population of motoneurons firing in a statistically independent way, which reduces the variability of the population firing. These data show that reproducible spike trains are not required to sustain reproducible behaviors and illustrate how the nervous system can cope with unreliable components to produce reliable action.


Study of the association between gait variability and gene expressions in a mouse model of transient focal ischemic stroke.
Purpose: Gait variability analysis has been clinically adopted to characterize the presentation of various neurological diseases. However, literature and practice lack a comprehensive murine model assessment of the gait deficits that result from transient focal ischemic stroke. Further, correlations between gait parameters and the gene expression profiles associated with brain ischemia have yet to be identified. This study quantitatively assesses gait deficits through a murine model of transient focal cerebral ischemia on day 7 to determine associations between gait deficits and ischemia-related gene expressions.Methods: A total of 182 dynamic and static gait parameters from the transient middle cerebral artery occlusion (MCAO) murine model for simulating human transient focal ischemic stroke on day 7 were measured using the CatWalk system. Pearson's correlation analysis and genes associated with ischemia were identified from the existing literature to aid the investigation of the relationship between gait variability and gene expression profiles.Results: Thirty-nine gait parameters and the mRNA expression levels of four of the eight ischemia-associated genes exhibited more significant change in the MCAO models (p < 0.005) on day 7. Twenty-six gait parameters exhibited strong correlations with four ischemia-associated genes.Conclusion: This examination of gait variability and the strong correlation to the gene expression profiles associated with transient focal brain ischemia on day 7 provides a quantitative and reliable assessment of the MCAO model's motor performance. This research provides valuable insights into the study of disease progression and offers novel therapeutic interventions in the murine modeling of ischemic stroke.


Effects of gruel feeding and oral dextrose on the survivability of pigs after weaning.
Two experiments were conducted in a 14,400 head nursery using 3,087 (experiment 1) and 988 (experiment 2) pigs to determine the effect of gruel feeding (experiment 1) and supplemental oral dextrose (experiment 2) on nursery pig survivability after weaning. Upon arrival to the nursery, for experiment 1, the smallest 10% of pigs were selected and randomly placed in pens with 61 to 108 pigs per pen. Pens of small pigs were assigned to one of two treatments in a completely randomized design. Treatments consisted of gruel feeding two or four times per day for 14 d postplacement. At each gruel feeding, approximately 1.13 kg of solid feed was added to a round bowl (Rotecna S.A., Agramunt, Spain) located at the front of each pen and water added at a decreasing rate over time. In experiment 2, every other pig removed for welfare considerations (lameness, sick, or unthrifty) from the general population or pens of small pigs received a single 10 mL oral dose of a 50% dextrose solution (Vet One, MWI Animal Health, Boise, ID), as a source of glucose, before being placed in a removal pen. All removed pigs were tagged and weighed, body temperature recorded, and blood glucose concentration measured prior to and 30 min after entering removal pens. Overall, gruel feeding small pigs two or four times per day for 14 d postplacement did not influence (P > 0.10) mortality from weaning to the end of gruel feeding (3.78% vs. 4.25%, respectively). Likewise, dextrose administration did not influence (P > 0.10) pig mortality after removal to approximately 38 d postweaning (21.4% vs. 23.4% respectively), even though blood glucose concentration increased (P < 0.001) 30 min after removal for pigs administered dextrose. An interaction was observed for blood glucose concentration and body temperature (P < 0.001) where pigs with blood glucose concentrations less than 70 mg/dL had increased mortality as body temperature increased. In contrast, pigs with a blood glucose concentration of 70 mg/dL or greater had decreased mortality as body temperature increased. Pigs weighing less than 4.5 kg also had increased mortality (P < 0.001) compared with pigs weighing greater than or equal to 4.5 kg at removal. In summary, gruel feeding four times per day vs. two times per day or providing a dextrose supplement to pigs removed from the general population did not improve the survivability of pigs after weaning. Additionally, pigs removed with decreased body weight or with body temperature or blood glucose concentrations below or above the normal range had decreased survivability.


Cellular distribution of torsin A and torsin B in normal human brain.
Early-onset torsion dystonia is a hyperkinetic movement disorder caused by a deletion of 1 glutamic acid residue in torsin A protein, a novel member of the AAA family of adenosine triphosphatases. No mutation has been found so far in the closely related torsin B protein. Little is known about the molecular basis of the disease, and the cellular functions of torsin proteins remain to be investigated. To study the regional, cellular, and subcellular distribution of the torsin A and torsin B proteins. Expression of torsin proteins in the central nervous system was analyzed by Western blot analysis and immunohistochemistry in human postmortem brain tissues. We generated polyclonal antipeptide antibodies directed against human torsin A and torsin B proteins. In Western blot analysis of normal human brain homogenates, the antibodies specifically recognized 38-kd endogenous torsin A and 62-kd endogenous torsin B. Absorption controls showed that labeling was blocked by cognate peptide used for immunization. Immunolocalization studies revealed that torsin A and torsin B were widely expressed throughout the human central nervous system. Both proteins displayed cytoplasmic distribution, although torsin B localization in some neurons was perinuclear. Strong labeling of neuronal processes was detected for both proteins. Torsin A and torsin B have similar distribution in the central nervous system, although their subcellular localization is not identical. Strong expression in neuronal processes points to a potential role for torsin proteins in synaptic functioning.


[RAPD analysis of the intraspecific and interspecific variation and phylogenetic relationships of Aegilops L. species with the U genome].
RAPD analysis was used to study the genetic variation and phylogenetic relationships of polyploid Aegilops species with the U genome. In total, 115 DNA samples of eight polyploid species containing the U genome and the diploid species Ae. umbellulata (U) were examined. Substantial interspecific polymorphism was observed for the majority of the polyploid species with the U genome (interspecific differences, 0.01-0,2; proportion of polymorphic loci, 56.6-88.2%). Aegilops triuncialis was identified as the only alloploid species with low interspecific polymorphism (interspecific differences, 0-0.01, P = 50%) in the U-genome group. The U-genome Aegilops species proved to be separated from other species of the genus. The phylogenetic relationships were established for the U-genome species. The greatest separation within the U-genome group was observed for the US-genome species Ae. kotschyi and Ae. variabilis. The tetraploid species Ae. triaristata and Ae. columnaris, which had the UX genome, and the hexaploid species Ae. recta (UXN) were found to be related to each other and separate from the UM-genome species. A similarity was observed between the U M-genome species Ae. ovata and Ae. biuncialis, which had the UM genome, and the ancestral diploid U-genome species Ae. umbellulata. The UC-genome species Ae. triuncialis was rather separate and slightly similar to the UX-genome species.


Immune protection of microneme 7 (EmMIC7) against Eimeria maxima challenge in chickens.
In the present study, the immune protective effects of recombinant microneme protein 7 of Eimeria maxima (rEmMIC7) and a DNA vaccine encoding this antigen (pVAX1-EmMIC7) on experimental challenge were evaluated. Two-week-old chickens were randomly divided into five groups. Experimental groups of chickens were immunized with 100 μg DNA vaccine pVAX1-MIC7 or 200 μg rEmMIC7, while control groups of chickens were injected with pVAX1 plasmid or sterile phosphate buffered saline (PBS). The results showed that the anti-EmMIC7 antibody titres in chickens of both rEmMIC7 and pVAX1-MIC7 groups were significantly higher as compared to PBS and pVAX1 control (P < .05). The splenocytes from both vaccinated groups of chickens displayed significantly greater proliferation response compared with the controls (P < .05). Serum from chickens immunized with pVAX1-MIC7 and rEmMIC7 displayed significantly high levels of interleukin-2, interferon-γ, IL-10, IL-17, tumour growth factor-β and IL-4 (P < .05) compared to those of negative controls. The challenge experiment results showed that both the recombinant antigen and the DNA vaccine could obviously alleviate jejunum lesions, body weight loss and enhance oocyst decrease ratio. The anti-coccidial index (ACI) of the pVAX1-MIC7 group was 167.84, higher than that of the recombinant MIC7 protein group, 167.10. Our data suggested that immunization with EmMIC7 was effective in imparting partial protection against E. maxima challenge in chickens and it could be an effective antigen candidate for the development of new vaccines against E. maxima.


Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats.
The brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated. To analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment. Healthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography. Compared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of Proteobacteria at the level of phylum. While the abundances of Alistipes, Bacteroides, Prevotella, and Lactobacillus decreased significantly at the level of order, family, and genus, the abundances of Staphylococcaceae, Enterococci, Psychrobacter, and Oligella increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of Lactobacillaceae or Peptostreptococcaceae, and negatively correlated with that of Aerococcaceae, and Alcaligenaceae in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood. Alterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.


New priorities: Analysis of the New Kidney Allocation System on UCLA patients transplanted from the deceased donor waitlist.
UNOS implemented a new Kidney Allocation System (New KAS) on December 4, 2014 with a primary goal of increasing equity to organ transplant for patients that were immunologically or socially disadvantaged by the previous allocation system (Previous KAS) that prioritized long wait times. We examined the effects of the New KAS on patients transplanted from the UCLA deceased donor waitlist during the first year and compared to the last year of the Previous KAS. The total number of deceased donor kidney transplants was increased in the New KAS as compared to the Previous KAS (178 vs 148). Transplant of regraft patients and of highly sensitized patients with cPRA⩾99% was significantly increased in the New KAS (New KAS vs Previous KAS, 29.8% vs 11.5%, p⩽0.0001, and 26.4% vs 2.7%, p⩽0.0001, respectively). In the New KAS, the percentage of patient's receiving allografts imported from outside our local area was also significantly increased (34.8% vs 15.5%, p<0.0001). In the New KAS, 59.7% and 48.3% of imported organs were allocated to very highly sensitized (⩾99% cPRA) or re-graft patients, respectively, as compared to 8.7% and 8.7% during the Previous KAS (p<0.001). Recipients and donors with age differences exceeding 15years were decreased in the New KAS as compared to the Previous KAS (36.5 vs 48.7%, p⩽0.032). There was a 40.1% reduction in transplant to patients in the 65+ age group in the New KAS (p⩽0.025). The percentage of patients transplanted with preformed donor specific antibody (DSA) was similar in the New as compared to the Previous KAS (19.7% vs 15.5%) and, patients were transplanted with a range of 1-3 preformed DSA of weak to moderate strength. Cold ischemic time was significantly increased over all organs, and in patients transplanted with preformed DSA during the New as compared to the Previous KAS (17.5 vs 19.1h and 17.2 vs 22.2, p<0.04 and p<0.03, respectively). Episodes of delayed graft function and the number of biopsies for cause were similar between the New and the Previous KAS. However, there were more events of biopsy proven antibody mediated rejection in patients transplanted since the start of the New KAS. The data show that the New KAS is working at the center level as designed to better age match recipients and donors and to increase transplantation of very highly sensitized patients through broader sharing.


Cleft palate lateral synechia syndrome.
Cleft lip and palate are the most common congenital craniofacial anomaly in humans. The presence of oral synechia along with cleft palate is a rare syndrome. We encountered one case that had a cleft palate accompanied by congenital oral synechia due to a membranous adhesion between the floor of the mouth and the free margin of the cleft palate.


A longitudinal study of facial growth of Southern Chinese in Hong Kong: Comprehensive photogrammetric analyses.
Existing studies on facial growth were mostly cross-sectional in nature and only a limited number of facial measurements were investigated. The purposes of this study were to longitudinally investigate facial growth of Chinese in Hong Kong from 12 through 15 to 18 years of age and to compare the magnitude of growth changes between genders. Standardized frontal and lateral facial photographs were taken from 266 (149 females and 117 males) and 265 (145 females and 120 males) participants, respectively, at all three age levels. Linear and angular measurements, profile inclinations, and proportion indices were recorded. Statistical analyses were performed to investigate growth changes of facial features. Comparisons were made between genders in terms of the magnitude of growth changes from ages 12 to 15, 15 to 18, and 12 to 18 years. For the overall face, all linear measurements increased significantly (p < 0.05) except for height of the lower profile in females (p = 0.069) and width of the face in males (p = 0.648). In both genders, the increase in height of eye fissure was around 10% (p < 0.001). There was significant decrease in nasofrontal angle (p < 0.001) and increase in nasofacial angle (p < 0.001) in both genders and these changes were larger in males. Vermilion-total upper lip height index remained stable in females (p = 0.770) but increased in males (p = 0.020). Nasofrontal angle (effect size: 0.55) and lower vermilion contour index (effect size: 0.59) demonstrated large magnitude of gender difference in the amount of growth changes from 12 to 18 years. Growth changes of facial features and gender differences in the magnitude of facial growth were determined. The findings may benefit different clinical specialties and other nonclinical fields where facial growth are of interest.


A new class of ligands for aqueous, lanthanide-catalyzed, enantioselective Mukaiyama aldol reactions.
The development of aqueous methods for generating enantiopure β-hydroxy carbonyl compounds is an important goal because these subunits compose many bioactive compounds and the ability to synthesize these groups in water has environmental and cost benefits. In this communication, we report a new class of ligands for aqueous, lanthanide-catalyzed, asymmetric Mukaiyama aldol reactions for the synthesis of chiral β-hydroxy ketones. Furthermore, we have used luminescence-decay measurements to unveil mechanistic information regarding the catalytic reaction via changes in water-coordination number. The precatalysts presented here yielded β-hydroxy carbonyls from aliphatic and aryl substrates with outstanding syn:anti ratios and enantiometric excesses of up to 49:1 and 97%, respectively.


Electromyostimulation Application on Peroneus Longus Muscle Improves Balance and Strength in American Football Players.
The aim of this study was to evaluate the effect of 5 weeks of electromyostimulation (EMS) of the peroneus longus muscle on balance and muscle strength in American Football (AmF) players. Thirty-two healthy male athletes (4 American Football team training sessions per week, college level) were randomly divided into the EMS and control groups. The EMS applications were conducted on the dominant peroneus longus muscle 3 times per week for 5 weeks, with each application lasting 25 minutes. Before and after the interventions, the strength of ankle dorsiflexion-plantar flexion and foot eversion-inversion was measured with isometric dynamometer and anterior-posterior sway, mediolateral sway, perimeter, and ellipse area were measured with the Technobody Balance System in unilateral stance positions, while eyes were open. Changes between initial and final tests for dorsiflexion and eversion strength, and mediolateral sway for dynamic balance in the groups were significantly different (P = .039, P = .027, P = .030, respectively). The EMS application had positive effects on muscle strength and dynamic balance of AmF players. The EMS can be used to improve isometric strength and dynamic balance in AmF players.


Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice.
The involvement of mu-opioid receptors in different behavioral responses elicited by nicotine was explored by using mu-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of mu-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that mu-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.


Gain control in semiconductor quantum dots via state-resolved optical pumping.
Excitonic state-resolved optical pumping experiments were performed on strongly confined semiconductor quantum dots. We demonstrate for the first time that optical gain is dependent upon the initial excitonic state. By prescribing the specific multiexcitonic states which can create, block, and ultimately control optical gain spectra, we recover the theoretically predicted size independence, even in systems which previously showed zero gain. In addition, we show for the first time that stimulated emission in quantum dots can be controlled via specific multiexcitonic interactions.


II. Improved dark adaptation after carotid endarterectomy. Evidence of a long-term ischemic penumbra?
We have reported that dark vision is impaired in symptomatic carotid artery disease and that the impairment correlates with internal carotid artery stenosis. To find out whether this impairment is reversible after carotid endarterectomy, dark adaptation was examined pre- and postoperatively. Twenty-one consecutive patients were examined by dark adaptometry. Two examinations were done for each eye on two consecutive days pre- and postoperatively. Thirty-one matched control subjects were examined under identical conditions. The control subjects did not have clinical evidence of carotid artery disease. Patients and control subjects were free of ophthalmologic disorders. Dark vision frequently improved remarkably after endarterectomy. The average retinal sensitivity to light in darkness on the operated side doubled, and there was also improvement on the nonoperated side. There was no significant change in dark vision in the control subjects, negating a learning effect. The findings suggest the existence of reversible neuronal ischemia secondary to hemodynamic causes or frequent subclinical microembolization. Because the circulatory conditions are optimized, formerly inactive, surviving neurons may regain function.


Distalization of maxillary molars using a lever arm and mini-implant.
This article describes the orthodontic treatment of a young woman with a Class II malocclusion and maxillomandibular prognathism. One orthodontic mini- implant was placed in the posterior area of the palate to provide anchorage for?a transpalatal arch. The force for molar distalization was applied using an elastic chain from the lever arm inserted on the transpalatal arch to the mini-implant. Two sliding jigs were applied buccally as a complement for Class II malocclusion correction. This system created an efficient mechanotherapy for maxillary molar distalization. The active treatment period was 19 months. Normal overjet and reduction of maxillomandibular prognathism were obtained, and labial balance was improved.


Acute Kidney Injury Following Star Fruit Ingestion: A Case Series.
Star fruit (Averrhoa carambola) is a popular fruit in many tropical countries, including Sri Lanka. It is rich in oxalic acid, which is nephrotoxic in higher concentrations. The development of both acute (AKI) and chronic kidney injury after oxalate nephropathy is often underrecognized. Here we discuss the risk factors, clinical features, treatment, and outcomes of 4 patients who developed AKI after star fruit ingestion. Baseline clinical characteristics, the amount of star fruit ingested, clinical presentation, investigation, and outcome of the patients (ages 28, 50, 54, and 55 y; all male) were traced. More common symptoms of acute star fruit intoxication were nausea, vomiting, and abdominal and back pain, followed by low urine output and high serum creatinine over hours to days. Urinary analysis of all patients demonstrated oxalate crystals. Histopathologic examination of renal tissues of all 4 patients revealed acute tubular damage with calcium oxalate crystals, interstitial edema, and inflammatory cellular infiltration. The presence of calcium oxalate crystals was further confirmed with the brilliant birefringence seen under polarized light. Two patients needed intermittent hemodialysis over a week owing to oliguria and uremia. The other 2 patients did not require hemodialysis and had improvement of renal function with supportive treatment. All had high renal function on discharge but were back to normal within a month. This study highlights AKI as a serious complication of star fruit ingestion. The type and quantity of star fruit ingested and some patient factors may play a role in the pathogenesis of AKI. Public education about this serious uncommon complication is important.


Partial rehabilitation of the posterior edentulous maxilla using axial and tilted implants in immediate function to avoid bone grafting.
There is a need to create rehabilitation solutions for partial edentulism in the posterior maxilla, thereby reducing the need for grafting in these areas. The purpose of this study was to report the results of partial edentulism rehabilitation in the posterior maxilla with a three- to four-unit bridge supported by two implants: anterior implant placed in axial position and posterior implant tilted distally. A theoretical analysis of the concept including a biomechanical discussion is also provided. The clinical study included 35 patients (21 women, 14 men) with an age range of 37 to 80 years (mean = 55.5 years), rehabilitated with an implant-supported partial bridge, followed between 4 months and 8 years, with a mean follow-up time of 53 months. ASSESSMENT DATA:The success criteria included clinical parameters (ie, implant fulfilled its purported function as support for reconstruction; was stable when individually and manually tested; had absence of infection; demonstrated a good esthetic outcome of the rehabilitation; allowed fabrication of the implant-supported fixed prosthesis, which provided patient comfort and hygiene) and radiographic parameters (ie, implant probability of long-term stability, as judged by annual bone loss). The implant survival estimate was computed using the Kaplan-Meier product limit estimator. Data were analyzed with descriptive and inferential analyses. The survival rates were 97.1% and 98.8% at 8 years (Kaplan-Meier), using the patient and implant as units of analysis, respectively. The overall average marginal bone resorption was 1.05 mm (SD = 0.65 mm) at 1-year follow-up, and 1.47 mm (SD = 0.37 mm) at 5-year follow-up, with no significant differences between axial and tilted implants in the 1-year (P = 0.107) and 5-year (P = 0.211) evaluations. DISCUSSION OF RESULTS:The results indicate that within the limitations of this preliminary study the present protocol is valid for the rehabilitation of partial edentulism in the posterior maxilla. The clinical results confirmed the theoretical analysis on biomechanics and load distribution, with high survival and success rates in the long-term, low implant marginal bone resorption, and low frequencies of complications.


Biomechanical comparison of isokinetic lifting and free lifting when applied to chronic low back pain rehabilitation.
The study compares free and isokinetic lifting using a multivariate statistical analysis. Each of the 13 male subjects performed three free lifts and three isokinetic lifts using a CYBEX LIFTASK. The measurement variables were obtained from a 3D video system, two force plates and two strain-gauge transducers. Coupling of fuzzy space-time windowing and multiple correspondence analysis was used to show the links between the variables and the differences between the experimental situations. Isokinetic lifting had almost no points in common with free-lifting, but there was a similar range of extension for the different joints. Most free-lifting strategies could not be used in isokinetic lifting, as constraints between the subject and his environment were different. The main drawback of the isokinetic lifting was due to the necessity for individuals to reach the machine speed, yielding high transient efforts. The maximum vertical effort at the L5/S1 joint was about 1600, 1500 and 1400N for low, medium and high speed, whereas it was lower than 1300N, irrespective of the load, during free lifting. In the context of chronic low back pain rehabilitation, movement strategies used in free lifting could not be relearnt using an isokinetic machine. A better understanding of the common points and differences between isokinetic movement and free movement could help rehabilitation physicians to plan rehabilitation programmes, taking advantage of each kind of movement.


Effect of whitening dentifrices on the surface roughness of commercial composites.
Our study aimed to test the null hypothesis that whitening and non-whitening dentifrices affect similarly the surface roughness of commercial microhybrid composites, independent of the brushing time. One hundred and ninety-two disc-shaped specimens of Filtek Z250 (3 M/ESPE, St. Paul, MN, USA) and Rok (SDI, Australia) were built up and randomly assigned to 24 groups, based on the dentifrices used (two whitening dentifrices: Colgate Max White-Colgate-Palmolive, São Bernardo do Campo, São Paulo, Brazil and Close Up Extra Whitening-Unilever, Brasil Higiene Pessoal e Limpeza Ltda, Ipojuca, Pernambuco, Brazil; and one non-whitening dentifrice: Colgate Total 12 Clean Mint-Colgate-Palmolive), and on the simulated brushing times (24 hours, 6, 12 and 24 months). The specimens were submitted to the toothbrushing regimens after which the surface roughness (Ra) was measured. Data was submitted to analysis of variance and Tukey test (α=0.05). The composite's surface roughness was significantly affected by the composites (p=0.0007), the dentifrices (p=0.0001), and the simulated brushing time (p=0.0001). Higher roughness was observed when the whitening dentifrices were used and when the brushing time increased. Filtek Z250 was more affected than Rok, especially after 24 months of simulated brushing. Whitening dentifrices produced higher surface roughness in the composites tested. The degree of surface compromising increased with brushing time and depends on the composite's microstructure and composition.


Comparison of DSM-II and DSM-III schizophrenics: a longitudinal perspective.
Patients who meet DSM-III criteria for schizophrenia were compared with those who meet DSM-II, but not DSM-III, criteria. Comparisons included measures of positive symptoms, negative symptoms, and social competence both before extended hospitalization and during a 7-year follow-up. The measure of positive symptoms was the only variable that differed significantly between groups at initial assessment. Positive symptoms were more stable and predictive for DSM-III schizophrenics than for DSM-II schizophrenics. The measure of negative symptoms was the most stable and predictive variable for the DSM-II schizophrenics. Increased homogeneity for the DSM-III schizophrenics was not found for most measures.


Optimizing Few-Shot Learning Based on Variational Autoencoders.
Despite the importance of few-shot learning, the lack of labeled training data in the real world makes it extremely challenging for existing machine learning methods because this limited dataset does not well represent the data variance. In this research, we suggest employing a generative approach using variational autoencoders (VAEs), which can be used specifically to optimize few-shot learning tasks by generating new samples with more intra-class variations on the Labeled Faces in the Wild (LFW) dataset. The purpose of our research is to increase the size of the training dataset using various methods to improve the accuracy and robustness of the few-shot face recognition. Specifically, we employ the VAE generator to increase the size of the training dataset, including the basic and the novel sets while utilizing transfer learning as the backend. Based on extensive experimental research, we analyze various data augmentation methods to observe how each method affects the accuracy of face recognition. The face generation method based on VAEs with perceptual loss can effectively improve the recognition accuracy rate to 96.47% using both the base and the novel sets.


Ketone Synthesis by a Nickel-Catalyzed Dehydrogenative Cross-Coupling of Primary Alcohols.
An intermolecular coupling of primary alcohols and organotriflates has been developed to provide ketones by the action of a Ni(0) catalyst. This oxidative transformation is proposed to occur by the union of three distinct catalytic cycles. Two competitive oxidation processes generate aldehyde in situ via hydrogen transfer oxidation or (pseudo)dehalogenation pathways. As aldehyde forms, a Ni-catalyzed carbonyl-Heck process enables formation of the key carbon-carbon bond. The utility of this rare alcohol to ketone transformation is demonstrated through the synthesis of diverse complex and bioactive molecules.


COX-2 expression and cell cycle progression in human fibroblasts.
Cyclooxygenase-2 (COX-2) is continuously expressed in most cancerous cells where it appears to modulate cellular proliferation and apoptosis. However, little is known about the contribution of transient COX-2 induction to cell cycle progression or programmed cell death in primary cells. In this study we determined whether COX-2 regulates proliferation or apoptosis in human fibroblasts. COX-2 mRNA, protein, and prostaglandin E2 (PGE2) were not detected in quiescent cells but were expressed during the G0/G1 phase of the cell cycle induced by serum. Inhibition of COX-2 did not alter G0/G1 to S phase transition or induce apoptosis at concentrations that diminished PGE2. Addition of interleukin-1beta to serum enhanced COX-2 expression and PGE2 synthesis over that by serum alone but had no effect on the progression of these cells into S phase. Furthermore, platelet-derived growth factor drove the G0 fibroblasts into the cell cycle without inducing detectable levels of COX-2 or PGE2. Collectively, these data show that transient COX-2 expression in primary human fibroblasts does not influence cell cycle progression.


Design of a Variable Stiffness Soft Dexterous Gripper.
This article presents the design of a variable stiffness, soft, three-fingered dexterous gripper. The gripper uses two designs of McKibben muscles. Extensor muscles that increase in length when pressurized are used to form the fingers of the gripper. Contractor muscles that decrease in length when pressurized are then used to apply forces to the fingers through tendons, which cause flexion and extension of the fingers. The two types of muscles are arranged to act antagonistically and this means that by raising the pressure in all of the pneumatic muscles, the stiffness of the system can be increased without a resulting change in finger position. The article presents the design of the gripper, some basic kinematics to describe its function, and then experimental results demonstrating the ability to adjust the bending stiffness of the gripper's fingers. It has been demonstrated that the fingers' bending stiffness can be increased by more than 150%. The article concludes by demonstrating that the fingers can be closed loop position controlled and are able to track step and sinusoidal inputs.


Copper metabolic defects and liver disease: environmental aspects.
Copper (Cu) is an essential trace element for many biological processes. Cu homeostasis is generally well maintained by inbuilt controls in intestinal absorption, biliary excretion and intrahepatic storage. Copper deficiency disorders are rare. Acute Cu toxicity occurs occasionally in accidental poisoning with Cu sulfate. Chronic Cu toxicity in the form of liver cirrhosis and damage to other organs is seen classically in Wilson's Disease (genetic abnormality of Cu metabolism) and in the presumed environmental disorder Indian Childhood Cirrhosis (ICC). The clinical, epidemiological and treatment aspects of ICC are described. The evidence linking ICC to environmental Cu is (i) greatly increased hepatic Cu; (ii) early introduction of Cu contaminated milk boiled or stored in brass vessels; (iii) dramatic decline in ICC throughout the country coincident with change in feeding vessels; and (iv) continued long-term remission in d-penicillamine-treated patients after withdrawal of the drug. The nature and role of a second factor in the causation of ICC remains unclear, although a genetic predisposition is strongly suspected. Scattered reports of an ICC-like illness from the West (Idiopathic Cu Toxicosis, Endemic Tyrolean Infantile Cirrhosis), suggest that different mechanisms (environmental, genetic or both) can lead to the same end stage liver disease-'ecogenetic' disorders.


Senescence, sleep, and circadian rhythms.
The goal of this review article is to summarize our knowledge and understanding of the overlapping (interdisciplinary) areas of senescence, sleep, and circadian rhythms. Our overview comprehensively (and visually wherever possible), emphasizes the organizational, dynamic, and plastic nature of both sleep and circadian timing system (CTS) during senescent processes in animals and in humans. In this review, we focus on the studies that deal with sleep and circadian rhythms in aged animals and how these studies have closely correlated to and advanced our understanding of similar processes in ageing humans. Our comprehensive summary of various aspects of the existing research on animal and human ageing, both normal and pathological, presented in this review underscores the invaluable advantage of close collaboration between clinicians and basic research scientists and the future challenges inherent in this collaboration. First, our review addresses the common age-related changes that occur in sleep and temporal organization of both animals and humans. Second, we examine the specific modifications that often accompany sleep and CTS during aging. Third, we discuss the clinical epidemiology of sleep dysfunctions during ageing and their current clinical management, both pharmacological and non-pharmacological. Finally, we predict the possible future promises for complementary and alternative medicine (CAM) that pave the way to the emergence of a "Holistic Sleep Medicine" approach to the treatment of sleep disorders in the ageing population. Further studies will provide additional valuable insights into the understanding of both sleep and circadian rhythms during senescence.


89Strontium-induced bone marrow depression suppresses the early inflammatory response and fibrosis caused by intratracheal bleomycin.
To investigate the effect of bone marrow depression on the development of bleomycin-induced lung injury, F-344/Crl rats were given an intraperitoneal (IP) injection of 89SrCl2 (2 mCi/kg body weight) 7 days prior to the intratracheal (IT) instillation of 7.0 U/kg body weight bleomycin (Sr-bleomycin group). A second group of rats was given an IP injection of saline followed 7 days later by IT bleomycin (bleomycin group). Additional rats were given 89Sr IP and saline IT (Sr group) or saline IP and saline IT (saline group). Rats were sacrificed at 0, 3, 10, 21, and 30 days after the intratracheal instillations. 89Sr administration resulted in significantly lower numbers of circulating blood neutrophils and monocytes in the Sr-bleomycin group compared with the bleomycin group through at least the first 21 days following the IT instillations. Lymphocyte numbers were also depressed in the Sr-bleomycin group at days 3 and 21. Analysis of bronchoalveolar lavage fluid (BALF) revealed significantly reduced protein and lymphocyte numbers in the BALF from the 89Sr-bleomycin group compared with the bleomycin group at day 3, but not at later time points. Neutrophils in BALF were also lower (though not significantly) in the 89Sr-Bleomycin group at day 3. There was no difference in the number of BALF macrophages between the Sr-bleomycin and bleomycin groups at any time point throughout the study. Histology and morphometry showed the same trends as the BALF data with much less severe lesions in the 89SR-Bleomycin group compared with the bleomycin group at day 3, but not at later time points. At day 10, hydroxyproline values were significantly higher in the bleomycin group (47% increase above saline group) than the Sr-bleomycin group (only 18% increase above Sr group), but by day 21, there was no longer a significant difference between these two groups. These results demonstrate that bone marrow depression significantly suppresses the early inflammatory response and collagen deposition caused by a single IT dose of bleomycin, but has little effect on the resolution of bleomycin-induced injury.


Multiple primary intracranial tumors and association of intra- and extracranial tumors. An autopsy study.
In 37504 autopsies performed during the last 3 decades at the Department of Pathology of Albert Szent-Györgyi Medical University (Szeged, Hungary) gliomas were found in 498 cases. These gliomas were associated with other types of intra- or extracranial tumors in 1.2-3.2% of the cases. Despite the male predominance observed in other types of multiple tumors, the multiple intracranial tumors and the intracranial tumors associated with extracranial malignancies were more frequent in females (possible role of hormonal influences). A relatively frequent association of various intracranial tumors with gastrointestinal carcinomas and in one quarter of the cases with extracranial benign tumors indicates that genetic factors may be involved in the pathomechanism.


Effect of potassium channel openers in acute and chronic models of glaucoma.
Glaucoma is characterized by increased intraocular pressure (IOP). The effect of nicorandil and pinacidil on IOP in experimentally induced acute and chronic models of glaucoma and the mechanism of action involved were studied. New Zealand white rabbits were used for the study. After the measurement of IOP, nicorandil (1%), pinacidil (1%), and pilocarpine as standard (1%) were instilled topically into the left eye. The other eye served as control. Dextrose (5%) was used to induce acute glaucoma. IOP changes were recorded every 15 minutes until the pressure became normal. Freshly prepared α-chymotrypsin solution was introduced in the posterior chamber to induce chronic glaucoma. Rabbits with ocular hypertension were selected for the study. Similar drug solutions were used to study the effect on IOP. Glibenclamide, pilocarpine, and indomethacin (1%) were used to study the mechanism of action of both drugs. The IOPs were measured just prior to drug instillation and at suitable time intervals using a tonometer. Pretreatment with topical nicorandil and pinacidil significantly lowered the rise in IOP in the acute model. Nicorandil and pinacidil initially caused rise in IOP for 15-30 minutes in chronic glaucoma. This was followed by reduction in IOP. Pretreatment with indomethacin and pilocarpine did not modify the effect of nicorandil and pinacidil on IOP. Pretreatment with glibenclamide blocked IOP from the lowering effect of nicorandil and pinacidil. The oculohypotensive effect shown by these drugs appears to be attributable to enhancement of the aqueous humor outflow. This effect is perhaps mediated through potassium channels.


In vivo examination of the dynamic properties of the human heel pad.
The shock-absorbing characteristics of the heel pad in vivo were examined in adults (N = 16) and 7-year-old children (N = 5) using a drop-impact tester (wt = 5 kg). Impact velocities were 0.72 m/s and 0.93 m/s. It was found that in adults the average peak deceleration was 11.6 G at an impact velocity of 0.93 m/s. The maximum deformation of the heel pad was 11.3 mm, and the computed energy absorption during impact amounted to 79% (range = 75%-89%). These mechanical characteristics remained nearly the same even after 6 min of repeated impacts by the impact tester and even after a 10 km run. The children had larger values of peak deceleration and maximum deformation and smaller energy loss than the adults. It was concluded that the heel pad was a fairly effective shock attenuator and high energy absorber, and that these characteristics remain nearly unchanged even after a relatively long period of repeated impacts. It was also concluded that the mechanical properties of the children's heel pads were different from those of the adults.


Autistic spectrum disorder symptoms in children and adolescents with attention-deficit/hyperactivity disorder: a meta-analytical review.
Research identifies highly variable prevalence estimates for autism spectrum disorder (ASD) in children and adolescents with attention deficit hyperactivity disorder (ADHD), particularly between community and clinical samples, warranting quantitative meta-analyses to investigate the true prevalence of ASD in children and adolescents with ADHD. Studies were identified through a systematic literature search of PsycINFO, MEDLINE and Web of Science through January 2018. Twenty-two publications met inclusion criteria (total N = 61 985). Two random effects meta-analyses were conducted: (1) to identify the proportion of children and adolescents with ADHD that met criteria for ASD; and (2) to compare the severity of dimensionally-measured ASD symptomology in children and adolescents with and without ADHD. The overall pooled effect for children and adolescents with ADHD who met threshold for ASD was 21%. There was no significant difference between community samples (19%) and clinical samples (24%) or between US studies v. those from other countries. Children and adolescents with ADHD had substantially more dimensionally-measured ASD traits compared with those who did not have ADHD (d = 1.23). The findings provide further evidence that ADHD and ASD are associated in nature. Clinical and research implications are discussed.


Longitudinal associations between teasing and health-related quality of life among treatment-seeking overweight and obese youth.
To examine concurrent and prospective associations between perceptions of teasing and health-related quality of life (HRQOL) over the course of a behavioral/educational intervention and the subsequent year in a sample of overweight and obese children and adolescents. A clinical sample of 93 overweight or obese youths (ages 7-17 years) and 1 parent/guardian completed measures of teasing and HRQOL at pre- and posttreatment and follow-up assessments. Structural equation modeling was used to examine the factor structure of the measures and to assess prospective associations over a 15-month period. Results indicate that, concurrently, weight-related teasing is inversely associated with HRQOL and that, prospectively, HRQOL is inversely associated with subsequent teasing. Study findings are suggestive of a directional relationship with lower quality of life predicting subsequent higher levels of teasing. Results suggest the potential for interventions designed to improve HRQOL to reduce teasing experiences for overweight and obese youth.


Negative control of plasmid pSC101 replication by increased concentrations of both initiator protein and iterons.
Increased intracellular concentrations of the initiator protein Rep (or RepA) interfere with pSC101 DNA replication, and mutated Rep proteins that result in an increase in plasmid copy numbers do not inhibit the replication. A rep mutant (rep(inh)) defective in the inhibitory activity was isolated and found to be a new high copy number mutant. The inhibitory function of Rep was enhanced by the coexistence of directly repeated sequences (DR; iterons) in the replication origin region (ori), but not by the inverted repeat sequences (IR) in ori and the rep promoter. This synergistic effect of Rep and DR sequences for the replication inhibition was dependent on their intracellular concentrations. Considering that DR sequences are the specific binding sites of the Rep monomer form, the Rep monomer-DR complex might be responsible for the inhibition of the plasmid replication. Furthermore, the Rep monomer in the crude cell extracts facilitated dimerization of DR DNA fragments by DNA ligase. Neither synergistic inhibitory function with DR nor Rep mediated dimerization of DR DNA was observed in high copy number mutant Rep proteins. The role of the Rep-iteron complex in the copy number control of pSC101 is discussed.


African American/Black race, apolipoprotein L1 , and serum creatinine among persons with HIV.
Accurate estimation of kidney function is critical among persons with HIV (PWH) to avoid under-dosing of antiretroviral therapies and ensure timely referral for kidney transplantation. Existing estimation equations for kidney function include race, the appropriateness of which has been debated. Given advancements in understanding of race and the necessity of accuracy in kidney function estimation, this study aimed to examine whether race, or genetic factors, improved prediction of serum creatinine among PWH. This cross-sectional study utilized data from the Center for AIDS Research Network of Integrated Clinical Systems cohort (2008-2018). The outcome was baseline serum creatinine. Ordinary least squares regression was used to examine whether inclusion of race or genetic factors [ apolipoprotein-L1 ( APOL1 ) variants and genetic African ancestry] improved serum creatinine prediction. A reduction in root mean squared error (RMSE) greater than 2% was a clinically relevant improvement in predictive ability. There were 4183 PWH included. Among PWH whose serum creatinine was less than 1.7 mg/dl, race was significantly associated with serum creatinine ( β = 0.06, SE = 0.01, P < 0.001) but did not improve predictive ability. African ancestry and APOL1 variants similarly failed to improve predictive ability. Whereas, when serum creatinine was at least 1.7 mg/dl, inclusion of race reduced the RMSE by 2.1%, indicating improvement in predictive ability. APOL1 variants further improved predictive ability by reducing the RMSE by 2.9%. These data suggest that, among PWH, inclusion of race or genetic factors may only be warranted at higher serum creatinine levels. Work eliminating existing healthcare disparities while preserving the utility of estimating equations is needed.


Liberal Norms and Their Discontents.
Recent analyses of the predominance of liberals in personality and social psychology have raised the possibility that this ideological imbalance is driven in part by active discrimination against conservatives. In this article, I review empirical evidence relevant to this possibility and find little support for it. The evidence points instead to a predominance of liberal views in academia more generally, driven by multiple factors including the consonance of academic work with the goals and values of liberals. Within the field of personality and social psychology, this concentration of liberal views has fostered strong liberal norms, which both intensify and exaggerate the field's ideological homogeneity. These liberal norms have unfortunate narrowing effects on research in personality and social psychology; remedies for these effects should focus on weakening the norms.


Dietary Copper Intake and Risk of Stroke in Adults: A Case-Control Study Based on National Health and Nutrition Examination Survey 2013-2018.
The association between dietary copper intake and the risk of stroke is unknown. We included a total of 10,550 participants from the National Health and Nutrition Examination Survey (NHANES) 2013−2018. Two 24-h dietary recalls and a standard questionnaire were used to determine copper intake and stroke, respectively. We used logistic regression models to estimate the associations between dietary copper intake and the risk of stroke. The nearest-neighbor propensity score matching (PSM) with a ratio of 1:2 was used to reduce selection bias. The non-linear relationship was explored with restricted cubic splines (RCS). The correlation between copper intake and baseline characteristics was detected by the Pearson correlation coefficient. The median dietary copper intake was 1.072 mg/day (IQR = 1.42−0.799). Approximately 3.8% (399) of the participants had a history of stroke. A multivariate logistic regression analysis before and after matching showed that subjects in the higher quartile had significantly lower odds of stroke compared with subjects in the first quartile of copper intake. A stratified analysis showed that copper intake was a significant protective factor for women, individuals <65 years old, individuals with hypertension, individuals who smoke, and diabetic stroke patients. The RCS models showed an L-shaped nonlinear relationship (p for nonlinear < 0.001) between copper intake and stroke. Our results suggested that increased dietary copper intake was associated with a lower risk of stroke.


Comparison of Using Second-Generation Cryoballoon and Radiofrequency Catheter for Atrial Fibrillation Ablation in Patients With the Common Ostium of Inferior Pulmonary Veins.
Aims: To compare the procedural outcomes of cryoballoon ablation (CBA) and radiofrequency ablation (RFA) in atrial fibrillation (AF) patients with the common ostium of inferior pulmonary veins (COIPV) and to explore the effect of COIPV on CBA performance through the assessment of anatomical factors. Methods: A total of 18 AF patients with COIPV were included. Pulmonary vein isolation (PVI) was performed with second-generation CBA or RFA. The anatomical characteristics of COIPV and procedural outcomes were collected. Results: The prevalence of COIPV was 0.82% in the enrolled population. PVI was achieved in all pulmonary veins (PVs) without any complications. The "tricircle" strategy was applied for RFA, and the segmental freeze strategy was performed for CBA. Compared with RFA, CBA had shorter procedural time (median: 53.0 vs. 78.0 min, p < 0.001) and longer fluoroscopy time (median: 13.5 vs. 6.0 min, p < 0.001). Higher ovality index of the ostium was seen in patients with ≥4 freezes in inferior PVs [IPVs; 0.95 (0.78-1.05) vs. 0.49 (0.21-0.83), p = 0.047]. During a median of 23.5 months of follow-up, the atrial arrhythmias-free survival after the procedure was comparable between CBA and RFA (p = 0.729). Conclusion: The second-generation CBA is an efficient and safe alternative for RFA in AF patients with COIPV. Anatomical characteristics of COIPV bring the challenge to the procedure performance of RFA and CBA.


Management of neck of femur fracture in an adult with short stature and learning disability.
Neck of femur fractures (NOFF) are one of the major health concerns, with their incidence and the cost of care rising each year. Though a plethora of literature remains available on NOFF and its management, we found very little evidence for management of NOFF in patients with short stature and learning disability. Because of this unique combination of conditions in our patient, we had to deviate from the standard practice in terms of the implant choice. The usage of cemented Asian C stem AMT with a 36 mm metallic head which is normally reserved for total hip replacements, helped us obtain the desired hip joint stability. This was supplemented by early involvement of the learning disability physiotherapy team and eventually the patient had a satisfactory outcome at 8 months of follow-up. This rare amalgamation of NOFF, short stature and learning disability deserves more attention which our case report hopes to achieve.


Lack of evidence for recipient precursor cells replenishing β-cells in transplanted islets.
Bone marrow and tissue precursor cells have been postulated to replenish grafts of transplanted islets. Several investigators have reported that bone marrow cells can promote the regeneration of injured islets. In this study, we investigated the potential of recipient-derived precursor cells to form new pancreatic endocrine cells in islet grafts transplanted under the kidney capsule. Mouse insulin promoter (MIP)-green fluorescence protein (GFP) mice, which express GFP only in β-cells, or β-actin GFP mice, which express GFP ubiquitously, were used to determine if the recipient-derived cells differentiate into β-cells or other types of endocrine cells. We transplanted MIP-GFP islets into wild-type mice, wild-type islets into MIP-GFP mice, β-actin GFP islets into wild-type mice, and wild-type islets into β-actin GFP mice. β-Actin GFP bone marrow cells were then injected into wild-type mice to evaluate the potential role of bone marrow stem cells to provide new islet cells to the graft. No β-cells with green fluorescence were seen in the graft when wild-type islets were transplanted into MIP-GFP mice. When wild-type islets were transplanted into β-actin GFP mice, no β-cells with GFP staining could be identified in the grafts. Similarly, no endocrine cells with GFP staining could be identified in the grafts after injection of β-actin GFP bone marrow cells into wild-type islet-transplanted wild-type mice. This study provides further support for the concept that recipient precursor cells do not produce new β-cells in grafts of transplanted islets.


Inhibitory effects of donepezil hydrochloride (E2020) on cholinesterase activity in brain and peripheral tissues of young and aged rats.
Donepezil hydrochloride (donepezil: E2020: (+/-)-2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-indan-1-one monohydrochloride)) is a centrally acting acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, its inhibitory effect on the activity of cholinesterase ex vivo was evaluated in the brain, plasma, erythrocytes, heart, small intestine, liver and pectoral muscle of young adult as well as aged rats, in comparison with that of tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride). In aged animals, cholinesterase activity in heart, small intestine and pectoral muscle was lower, whereas that in plasma and liver was higher than in young rats. Both groups showed the highest levels in the brain. Donepezil, at doses of 1.25, 2.5 and 5 mg/kg, p.o., inhibited brain, plasma, erythrocyte, liver and pectoral muscle cholinesterase activity in young rats in a dose-dependent manner but had less effect on cholinesterase activity in heart and small intestine. In aged animals, inhibition of cholinesterase activity in the brain, erythrocytes and pectoral muscle by donepezil was more potent than that in young animals. Tacrine, at doses of 5, 10 and 20 mg/kg, p.o., dose-dependently inhibited cholinesterase activity in all tissues of both young and aged animals, but most potently in heart, small intestine and liver. The inhibition of cholinesterase activity by tacrine in the brain, plasma, erythrocytes, heart and liver was more potent in aged rats than in tissues of young rats. Brain and plasma concentrations of unchanged donepezil and tacrine were measured in the same animals as used for the cholinesterase inhibition study. Brain and plasma concentrations of donepezil and tacrine were higher in aged than in young animals. It is concluded that the inhibitory effects of donepezil and tacrine on cholinesterase activity are greater in aged than in young rats, owing to differences in the tissue concentrations of these compounds between young and aged animals. It is also suggested that the effect of donepezil on cholinesterase activity is more tissue-selective than that of tacrine.


Knowledge of pre-eclampsia in women living in Makole Ward, Dodoma, Tanzania.
Pre-eclampsia is a hypertensive disorder specific to pregnancy responsible for significant maternal morbidity and mortality in Africa. The majority of deaths related to pre-eclampsia could be avoided with timely and effective care. "Phase one delays" arise because of lack of knowledge. This study aimed to assess the knowledge levels of women living in Makole ward, comparing respondent subgroups with different demographic characteristics. It also aimed to compare knowledge levels in respect to six subtopics of pre-eclampsia. This was to allow for planning of appropriate activities to reduce delays in seeking health care. This study surveyed 200 adult women randomly identified in the community. They were asked 36 questions on pre-eclampsia requiring yes / no answers. The data was analysed quantitatively. Overall knowledge levels were low with an average of 41% of correct answers. Minor differences in the knowledge levels of demographic subgroups were found. Statistically significant differences were identified between sub-topics of pre-eclampsia; signs and symptoms were the least well known. Educational systems (formal and informal) are failing to provide communities with potentially life-saving information. Health centre, community and school based education programmes are recommended.


Identification of six endogenous gibberellins in spinach shoots.
Analysis of highly purified extracts from spinach shoots by combined gas chromatography-mass spectrometry has demonstrated the presence of six 13-C-hydroxylated gibberellins (GAs): GA(53), GA(44), GA(19), GA(17), GA(20), and GA(29). The major GAs were GA(17), GA(19), and GA(20), whereas the other three GAs occurred in trace amounts. Structural considerations suggest that the six GAs identified in spinach are related in the following metabolic sequence: GA(53) --> GA(44) --> GA(19) --> GA(17) --> GA(20) --> GA(29).


A fusion of the Bacteroides fragilis ferrous iron import proteins reveals a role for FeoA in stabilizing GTP-bound FeoB.
Iron is an essential element for nearly all organisms, and under anoxic and/or reducing conditions, Fe2+ is the dominant form of iron available to bacteria. The ferrous iron transport (Feo) system is the primary prokaryotic Fe2+ import machinery, and two constituent proteins (FeoA and FeoB) are conserved across most bacterial species. However, how FeoA and FeoB function relative to one another remains enigmatic. In this work, we explored the distribution of feoAB operons encoding a fusion of FeoA tethered to the N-terminal, G-protein domain of FeoB via a connecting linker region. We hypothesized that this fusion poises FeoA to interact with FeoB to affect function. To test this hypothesis, we characterized the soluble NFeoAB fusion protein from Bacteroides fragilis, a commensal organism implicated in drug-resistant infections. Using X-ray crystallography, we determined the 1.50-Å resolution structure of BfFeoA, which adopts an SH3-like fold implicated in protein-protein interactions. Using a combination of structural modeling, small-angle X-ray scattering, and hydrogen-deuterium exchange mass spectrometry, we show that FeoA and NFeoB interact in a nucleotide-dependent manner, and we mapped the protein-protein interaction interface. Finally, using guanosine triphosphate (GTP) hydrolysis assays, we demonstrate that BfNFeoAB exhibits one of the slowest known rates of Feo-mediated GTP hydrolysis that is not potassium-stimulated. Importantly, truncation of FeoA from this fusion demonstrates that FeoA-NFeoB interactions function to stabilize the GTP-bound form of FeoB. Taken together, our work reveals a role for FeoA function in the fused FeoAB system and suggests a function for FeoA among prokaryotes.


[Simultaneous determination of norepinephrine and epinephrime in plasma by using high performance liquid chromatograph].
A sensitive and rapid method was reported for the determination of nerepinephrine (NE) and epinephrine (E) in plasma by using high-performance liquid chromatography with an electrochemical detector (HPLC-EC) and YWG-C18 column(5u). 3,4-Dihydroxybenzylamine(DHBA) was used as an internal standard. The mobile phase of 0.05 mol/L actate buffer(pH3.0)-methanol-0.05 mol/L EDTA-Na2(78:20:2) with of 200 mg/L SDS solution was pumped through the column with a flow rate of 1.0 ml/min. The lengths of retention time for NE, E and DHBA(IS) was 7.3 min, 8.3 min and 10.4 min, respectively. The standard curve was linear within the concentration range of 31.25 to 4000 ng/L for NE and E (NE: r = 0.9999 E: r = 0.9996). The within day RSD (%) were less than 1.87% for NE and less than 2.07% for E, inter-day RSD(%) were less than 8.92% for NE and less than 9.65% for E respectively. The average extraction recovery(%) for NE and E were 93.5% +/- 5.50% and 91.3% +/- 1.77% respectively. This method has been applied to the diagnosis of pheochromocytoma and clinical research.


Derivatization trends in capillary electrophoresis: an update.
This survey as a sequel of two earlier reports gives an overview of recent developments, starting from 1999, in the use of derivatization protocols in capillary electrophoretic (CE) analysis. Derivatization is mainly used for enhancement of the detection sensitivity in CE, for which a combination of fluorescence labeling and laser-induced fluorescence detection is favorable. Moreover, especially in the field of saccharide assay, derivatization to introduce charge into the molecule, is common. Derivatization procedures are classified in tables, focused on precapillary, on-line, on-capillary and postcapillary arrangements and divided in sections concerning the functional group that is derivatized. The most frequently reported groups are amines and the reducing end of (oligo)saccharides, but thiols, carbonyl and carboxyl groups, steroids and inorganic ions have also been reported about. Other reasons for derivatization are to enhance chiral separation, introduction of a suitable charge into the molecule or to improve mass spectrometric detection. The use of derivatization techniques for special cases, such as the analysis of neurotransmitters, insulin antibodies and mitochondria has also been incorporated as well as a study on the adsorption of proteins onto capillary walls during CE in which derivatization plays a role.


Electrochemical Oxidation Enables Regioselective and Scalable α-C(sp3)-H Acyloxylation of Sulfides.
A highly selective, environmentally friendly, and scalable electrochemical protocol for the construction of α-acyloxy sulfides, through the synergistic effect of self-assembly-induced C(sp3)-H/O-H cross-coupling, is reported. It features exceptionally broad substrate scope, high regioselectivity, gram-scale synthesis, construction of complex molecules, and applicability to a variety of nucleophiles. Moreover, the soft X-ray absorption technique and a series of control experiments have been utilized to demonstrate the pivotal role of the self-assembly of the substrates, which indeed is responsible for the excellent compatibility and precise control of high regioselectivity in our electrochemical protocol.


Peptide-based supramolecular hydrogels for bioimaging applications.
Owing to their superior loading capacity and biocompatibility, imaging agent-conjugated (or encapsulated) peptide-based supramolecular hydrogels are capable of imaging in vivo biological events with enhanced signals. Notably, by rational design of the hydrogelators, the hydrogelation process can "smartly" occur on the pathological site (or region of interest), rendering precise and sensitive bioimaging of the disease (or event) in vivo. Considering their importance in disease diagnosis, herein, we provide a review on the recent advances in peptide-based supramolecular hydrogels for bioimaging applications. Besides, we provide an outlook on the challenges (or chances) for these types of biomaterials in the field of bioimaging.


Preoperative embolization of renal tumours using balloon catheters.
Preoperative embolization was used in a series of 13 patients for reducing the bleeding during operation of even very large renal carcinomas. During and after embolization pain occurred which necessitated treatment. Balloon catheter embolization was used which excludes the risk of reflux of embolizing material to the aorta. It caused none or only minor injury to the renal arterial wall. No serious complication occurred.


[Italian Society of Cardiology (SIC) Position paper: Technical, instrumental and standards of interpretation for electrocardiography, ambulatory electrocardiographic and blood pressure monitoring in telemedicine].
The current COVID-19 pandemic has renewed interest in providing healthcare services based on the implementation of innovative technologies. Such strategy capillarizes the therapeutic opportunities for larger urban areas, mostly when people are living under extraordinarily difficult circumstances. Improving care delivery in cardiovascular diseases appears particularly feasible when telemedicine is pursued, especially with regard to baseline standard 12-lead electrocardiography, ambulatory electrocardiographic monitoring, and 24-hour ambulatory blood pressure monitoring. Nowadays, these first-line cardiovascular examinations are also available in health centers and pharmacies, and in recent months, there has been an increasing demand of such local services in the absence of specific rules and regulations regarding technical requirements and standards of interpretation that ensure a high quality clinical consultation.The purpose of this position paper is to provide critical requirements for the type/model of devices to be used, training dedicated to healthcare personnel, ensuring security of sensitive data, highlighting type of platforms to be used, as well as for maintaining high reporting quality and standards.


Malate Dehydrogenases in Guard Cells of Pisum sativum.
Guard cell protoplasts of Pisum sativum show considerable NADP-dependent malate dehydrogenase (MDH) activity in darkness which can be enhanced severalfold by illumination or treatment with dithiothreitol (DTT). The question arose whether guard cells possess an NADP-MDH different from that present in the chloroplasts of the mesophyll (which is inactive in darkness or in the absence of DTT). MDH activities were determined in extracts of isolated protoplasts from mesophyll and epidermis, and in mechanically prepared epidermal pieces (with guard cells as the only living cells and no interference from proteases originating from the cell wall digesting enzymes). Guard cells possessed NAD-dependent MDHs of high activity and incomplete exclusion of NADP as a coenzyme. This NADP-dependent activity of the NAD-MDH(s) could not be stimulated by DTT or, inferentially, by light. The DTT- (and light-) dependent NADP-MDH represented 0.05% of the total protein of the guard cells and had a specific activity of 0.1 unit per milligram protein; both values are in the same range as the corresponding ones of the mesophyll cells. Agreement was also found in the extent of light activation, in subunit molecular weight, immunological cross-reactions, and in the behavior on an ion exchange column. The activity of the chloroplastic NADP-MDH in guard cells barely suffices to meet the malate requirement for stomatal opening in the light. It is therefore likely that NAD-MDHs residing in other compartments of the guard cells supplement the activity of the chloroplastic NADP-MDH particularly during stomatal opening in darkness.


Repetitive nasal allergen challenge in allergic rhinitis: Priming and Th2-type inflammation but no evidence of remodelling.
Local tissue eosinophilia and Th2 cytokines are characteristic features of seasonal allergic rhinitis. Airway remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. Twelve patients with moderate-severe AR underwent 5 alternate day challenges with diluent which after 4 weeks were followed by 5 alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and submucosal inflammatory cells and remodelling markers were evaluated by computed image analysis. There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both P < .05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (P < .01, P = .01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r = 0.79, P = .007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r = 0.69, P = .06) in allergic rhinitis. No differences were observed after RAC with regard to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared with healthy controls. Novel repetitive nasal allergen challenge in participants with severe persistent seasonal allergic rhinitis resulted in tissue eosinophilia and increases in IL-5 but no structural changes. Our data support no link between robust Th2-inflammation and development of airway remodelling in AR.


Intraoperative patient information handover between anesthesia providers.
Currently, no reported studies have evaluated intraoperative handover among anesthesia providers. Studies on anesthetic handover in the US recovery room setting observed that handover processes are insufficient and, in many instances, significant intraoperative events are disregarded. An online survey tool was sent to anesthesia providers at US anesthesia residency programs nationwide (120 out of the 132 US programs encompassing around 4500 residents and their academic MDAs) and a smaller survey selection of CRNAs (10 institutions about 300 CRNAs in the metropolitan area of Detroit, MI, USA) to collect information on handover practices. The response rate to this survey (n = 216) was comprised of approximately 5% (n = 71) of the resident population in US anesthesia programs, 5% (n = 87) of MDAs , and 20% (n = 58) of the CRNAs. Out of all respondents (n = 212), 49.1 % had no hand-over protocol at their institution and 88% of respondents who did have institutional handover protocols believed them insufficient for effective patient handover. In addiiton, 84.8% of all responders reported situations where there was insufficient information received during a patient handover. Only 7% of the respondents reported never experiencing complications or mismanagement due to poor or incomplete hand-overs. In contrast, 60% reported rarely having complications, 31% reported sometimes having complications, and 3% reported frequent complications. In conclusion, handover transition of patient care is a vulnerable and potentially life-threatening event in the operating room. Our preliminary study suggests that current intraoperatvive handover practices among anesthesia providers are suboptimal and that national patient handover guidelines are required to improve patient safety.


The method of local increments for the calculation of adsorption energies of atoms and small molecules on solid surfaces. Part I. A single Cu atom on the polar surfaces of ZnO.
The method of local increments is used in connection with the supermolecule approach and an embedded cluster model to calculate the adsorption energy of single Cu atoms at different adsorption sites at the polar surfaces of ZnO. Hartree-Fock calculations for the full system, adsorbed atom and solid surface, and for the fragments are the first step in this approach. In the present study, restricted open-shell Hartree-Fock (ROHF) calculations are performed since the Cu atom possesses a singly-occupied 4s orbital. The occupied Hartree-Fock orbitals are then localized by means of the Foster-Boys localization procedure. The correlation energies are expanded into a series of many-body increments which are evaluated separately and independently. In this way, the very time-consuming treatment of large systems is replaced with a series of much faster calculations for small subunits. In the present application, these subunits consist of the orbitals localized at the different atoms. Three adsorption situations with rather different bonding characteristics have been studied: a Cu atom atop a threefold-coordinated O atom of an embedded Zn(4)O(4) cluster, a Cu atom in an O vacancy site at the O-terminated ZnO(000-1) surface, and a Cu atom in a Zn vacancy site at the Zn-terminated ZnO(0001) surface. The following properties are analyzed in detail: convergence of the many-body expansion, contributions of the different n-body increments to the adsorption energy, treatment of the singly-occupied orbital as "localized" or "delocalized". Big savings in computer time can be achieved by this approach, particularly if only the localized orbitals in the individual increment under consideration are described by a large correlation adapted basis set, while all other orbitals are treated by a medium-size Hartree-Fock-type basis set. In this way, the method of local increments is a powerful alternative to the widely used methods like DFT or RI-MP2.


Seasonal ovarian cycle in freshwater teleost, Labeo rohita (Ham.) in Tarai region of Uttaranchal.
Seasonal ovarian cycle, based on histophysiological changes, and correlative variations in liver were studied in an Indian major carp, Labeo rohita reared in captivity under ambient environmental conditions in Tarai region of Uttaranchal. The oocyte features used for marking ovarian cycle included nuclear-ooplasmic ratio, yolk vesicle incorporation into ooplasm, number and size of nucleolus and differentiation of follicular layer. Based on these features the ovarian cycle in L. rohita was divided into five phases i.e. resting, preparatory, pre-spawning, spawning and post-spawning/regression. The resting and preparatory phases were characterized by the dominating presence of chromatin-nucleolar and yolk-vesicle stage oocytes. The pre-spawning phase ovary was marked by the prevalence of yolk globule stage oocytes having cortical alveoli and differentiating follicular wall. The oocytes containing densely packed yolk-granules and large masses of yolk vesicles and also exhibiting germinal vesicle movement (GVM) signified the ovary of spawning phase. The ovary in regression phase contained pre-ovulatory atretic oocytes and significant number of oogonia. The histophysiological changes in liver showing augmented biosynthetic activity during preparatory and pre-spawning phases seemed well correlated with the gonadal development. The increasing water temperature and day-length apparently was favourable for the gonadal development in L. rohita.


Dual regulation of phospholipase D1 by protein kinase C alpha in vivo.
The regulation of phospholipase D1 (PLD1), which has been shown to be activated by protein kinase C (PKC) alpha, was investigated in the human melanoma cell lines. In G361 cell line, which lacks PKCalpha, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced PLD activation was potentiated by introducing PKCalpha by the adenovirus vector. The kinase-negative PKCalpha elevated TPA-induced PLD activity less significantly than the wild type. A PKC specific inhibitor GF109203X lowered PLD activation in the cells expressing PKCalpha, but did not prevent PLD potentiation induced by the kinase-negative PKCalpha. Expression of PKCbetaII and the kinase-negative PKCbetaII enhanced TPA-stimulated PLD activity moderately in MeWo cell line, in which PKCbetaII is absent. Furthermore, the TPA treatment increased the association of PKCalpha, PKCbetaII, and their kinase-negative mutants with PLD1 in melanoma cells. These results indicate that PLD1 is dually regulated through phosphorylation as well as through the protein-protein interaction by PKCalpha, and probably by PKCbetaII, in vivo.


Development and Validation of a Radiomics Nomogram for Predicting Clinically Significant Prostate Cancer in PI-RADS 3 Lesions.
To develop and validate a radiomics nomogram for the prediction of clinically significant prostate cancer (CsPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) category 3 lesions. We retrospectively enrolled 306 patients within PI-RADS 3 lesion from January 2015 to July 2020 in institution 1; the enrolled patients were randomly divided into the training group (n = 199) and test group (n = 107). Radiomics features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) imaging, and dynamic contrast-enhanced (DCE) imaging. Synthetic minority oversampling technique (SMOTE) was used to address the class imbalance. The ANOVA and least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection and radiomics signature building. Then, a radiomics score (Rad-score) was acquired. Combined with serum prostate-specific antigen density (PSAD) level, a multivariate logistic regression analysis was used to construct a radiomics nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate radiomics signature and nomogram. The radiomics nomogram calibration and clinical usefulness were estimated through calibration curve and decision curve analysis (DCA). External validation was assessed, and the independent validation cohort contained 65 patients within PI-RADS 3 lesion from January 2020 to July 2021 in institution 2. A total of 75 (24.5%) and 16 (24.6%) patients had CsPCa in institution 1 and 2, respectively. The radiomics signature with SMOTE augmentation method had a higher area under the ROC curve (AUC) [0.840 (95% CI, 0.776-0.904)] than that without SMOTE method [0.730 (95% CI, 0.624-0.836), p = 0.08] in the test group and significantly increased in the external validation group [0.834 (95% CI, 0.709-0.959) vs. 0.718 (95% CI, 0.562-0.874), p = 0.017]. The radiomics nomogram showed good discrimination and calibration, with an AUC of 0.939 (95% CI, 0.913-0.965), 0.884 (95% CI, 0.831-0.937), and 0.907 (95% CI, 0.814-1) in the training, test, and external validation groups, respectively. The DCA demonstrated the clinical usefulness of radiomics nomogram. The radiomics nomogram that incorporates the MRI-based radiomics signature and PSAD can be conveniently used to individually predict CsPCa in patients within PI-RADS 3 lesion.


200 consecutive laparoscopic pancreatic resections performed with a robotically controlled laparoscope holder.
Because of the potential benefit of robotics in pancreatic surgery, we review our experience at two minimally invasive pancreatic surgery centers that utilize a robotically controlled laparoscope holder to see if smaller robots that enable the operating surgeon to maintain contact with the patient may have a role in the treatment of pancreatic disease. From March 1994 to June 2011, a total of 200 laparoscopic pancreatic procedures utilizing a robotically controlled laparoscope holder were performed. A total of 72 duodenopancreatectomies, 67 distal pancreatectomies, 23 enucleations, 20 pancreatic cyst drainage procedures, 5 necrosectomies, 5 atypical pancreatic resections, 4 total pancreatectomies, and 4 central pancreatectomies were performed. Fourteen patients required conversion to an open approach and eight a hand-assisted one. A total of 24 patients suffered a major complication. Sixteen patients developed a pancreatic leak and 19 patients required reoperation. Major complications occurred in 14 patients and pancreatic leaks occurred in 13 patients. Ten patients required conversion to a lap-assisted or open approach and six patients required reoperation. Currently, a robotically assisted approach using a camera holder seems the only way to incorporate some of the benefits of robotics in pancreatic surgery while maintaining haptics and contact with the patient.


Altered Biodistribution and Hepatic Safety Profile of a Gapmer Antisense Oligonucleotide Bearing Guanidine-Bridged Nucleic Acids.
Guanidine-bridged nucleic acid (GuNA) is a novel 2',4'-bridged nucleic acid/locked nucleic acid (2',4'-BNA/LNA) analog containing cations that exhibit strong affinity for target RNA and superior nuclease resistance. In this study, Malat1 antisense oligonucleotide (ASO) bearing GuNA was evaluated for target knockdown (KD) activity and tolerability. The GuNA ASO did not interfere with RNase H recruitment on the target RNA/ASO heteroduplex and did show potent target KD activity in a skeletal muscle-derived cell line equivalent to that of the LNA ASO under gymnotic conditions, whereas almost no KD activity was observed in a hepatocyte-derived cell line. The GuNA ASO exhibited potent KD activity in various tissues; the KD activity in the skeletal muscle was equivalent with that of the LNA ASO, but the KD activities in the liver and kidney were clearly lower compared with the LNA ASO. In addition, despite the higher accumulation of the GuNA ASO in the liver, levels of aspartate aminotransferase and alanine aminotransferase with the GuNA ASO administration were not elevated compared with those induced by the LNA ASO. Our data indicate that the GuNA ASO is tolerable and exhibits unique altered pharmacological activities in comparison with the LNA ASO in terms of the relative effect between liver and skeletal muscle.


How Do Mental Health Nurses Define Success? A Comparative Study of Bed-Based and Community-Based Services.
Nursing is the single largest professional group within both hospital and community mental health care services, however the role of mental health nurses in under-defined. The nursing workforce is also coming under increasing pressure from internal and external requirements, and nurses themselves are on the frontline of providing patient care in what can be a risky and unpredictable workplace environment. This project explored via interview the ways in which mental health nurses experience and reflect on their personal and professional feelings of nursing success. Participants were 19 nurses who were employed in a range of bed-based and community mental health services in inner south eastern Melbourne. This study complies with the Consolidated Criteria for Reporting Qualitative Research (COREQ). The findings of the project align with existing evidence from the literature. Factors which helped mental health nurses feel successful included: therapeutic success; good teamwork; targeted education; and feedback. Barriers to success included: patients/clients do not engage or recover; poor communication amongst staff; lack of psychological safety in the workplace; and lack of respect from management. Nurses in community settings were more able than nurses in bed-based settings to: make effective use of clinical supervision; make use of targeted training and educational offerings; and practice therapeutically and holistically. Project results offer an opportunity to understand nurses' motivations and reward systems. Better understanding of these issues can improve the way mental health care services manage their workforce planning, maintain staff personal wellbeing, increase staff retention and ultimately improve patient/client care.


Effects of cholesterol on the function and thermotropic properties of pure UDP-glucuronosyltransferase.
The effects of cholesterol on the activity and thermal properties of a pure, delipidated isoform of UDP-glucuronosyltransferase were examined after incorporation of enzyme into unilamellar bilayers of distearoylphosphatidylcholine (DSPC) or dioleoylphosphatidylcholine (DOPC). Cholesterol, in bilayers of DSPC, decreased enzyme activity and lowered the temperature (from 37 to 30 degrees C) for a reversible transition from the active form of the enzyme to a less active form. These effects could be separated from each other in that the effect on reversible inactivation of the enzyme occurred at lower concentrations of cholesterol than the effect on activity of the active form of the enzyme. In addition, cholesterol in bilayers of DSPC stabilized UDP-glucuronosyltransferase against irreversible thermal inactivation. The extent of stabilization increased with increasing concentration of cholesterol in the bilayers. The effects of cholesterol on UDP-glucuronosyltransferase depended, however, on the nature of the bilayer containing cholesterol. Cholesterol had small effects, if any, on the properties of UDP-glucuronosyltransferase in bilayers of DOPC.


Exercise and Nutrition Interventions in Patients with Head and Neck Cancer during Curative Treatment: A Systematic Review and Meta-Analysis.
The aim of this meta-analysis was to examine the effects of nutritional and physical exercise interventions and interventions combining these interventions during radiotherapy treatment for patients with head and neck cancer on body composition, objectively measured physical function and nutritional status. Systematic electronic searches were conducted in MEDLINE (PubMed interface), EMBASE (Ovid interface), CINAHL (EBSCO interface) and Cochrane Library (Wiley interface). We identified 13 randomized controlled trials (RCTs) that included 858 patients. For body composition, using only nutrition as intervention, a significant difference between treatment and control group were observed (SMD 0.42 (95CI 0.23-0.62), p < 0.001). Only pilot RCTs investigated combination treatment and no significant difference between the treatment and control groups were found (SMD 0.21 (95CI -0.16-0.58), p = 0.259). For physical function, a significant difference between treatment and control group with a better outcome for the treatment group were observed (SMD 0.78 (95CI 0.51-1.04), p < 0.001). No effects on nutritional status were found. This meta-analysis found significantly positive effects of nutrition and physical exercise interventions alone in favor of the treatment groups. No effects in studies with combined interventions were observed. Future full-scaled RCTs combining nutrition and physical exercise is warranted.