Malignant melanoma in black Americans. A trend toward improved survival.
A search of patients seen at the Duke University Melanoma Clinic (Durham, NC) identified 79 black patients. Five- and 10-year survival was 35% and 26%, respectively. Patients presenting in the recent decade had less advanced disease, resulting in an improved 5-year survival of 49%. Five-year survival for white patients was 74%. Black patients had more negative prognostic indicators when compared with white patients. In a multivariate analysis, however, race was not a prognostic indicator, suggesting melanoma is not inherently more aggressive in black patients. The trend during the past decade has been for black patients to present with less advanced disease, with improved survival. This may be related to better appreciation of the disease by patients and physicians alike. Continued emphasis on education and early diagnosis may result in further improvement for black patients with melanoma.


British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections.
Outcomes for invasive fungal infections have greatly improved in the past decade, and several new antifungal drugs have been or will be licensed in the next few years. Early accurate diagnosis and appropriate treatment have major impact on survival. In a 1995 survey of laboratory practice in the UK for mycology, major disparities were seen, with many laboratories not undertaking even simple diagnostic procedures. Delays in processing and inadequate procedures for handling samples, incomplete or delayed reporting of results, or a combination of these, compromise the care of patients. In randomised trials of antifungal chemotherapy, optimum treatments and good alternatives for others have been defined for some infections. High-quality care requires a multidisciplinary approach to diagnosis and management. In this review, we propose microbiology, histopathology, radiology, and clinical auditing standards, with the evidence base for each reviewed. The standards are absolutes, and, therefore, provide a straightforward basis for improving services to patients if they are all implemented.


[Indices of the lipid spectrum of the blood serum and erythrocyte membranes in diabetes mellitus in children].
The paper is concerned with the results of a comparative study of the blood serum lipid spectrum and erythrocytic membranes in 100 children with diabetes mellitus aged 7 to 15 and 20 healthy children of the same age. The ratio of lipid and lipoprotein fractions depending on a degree of compensation, duration of disease and the presence of complications was disturbed in the blood serum and erythrocytic membranes of the diabetic children. The recovery of lipid metabolism was delayed as compared to clinical convalescence of the patients, therefore appropriate correcting therapy was required.


Nicotinamide's effects on glucose metabolism in subjects at risk for IDDM.
Nicotinamide is being used in trials to prevent or delay the development of clinical IDDM. A related compound, niacin, has been shown to cause insulin resistance in normal subjects, resulting in increased insulin secretion. This study was designed to answer the question: Does the short-term administration of nicotinamide cause insulin resistance in subjects who have a high risk of developing IDDM? Eight islet cell antibody-positive (ICA+) relatives of IDDM patients were given nicotinamide at a dose of 2 g/day for 2 weeks. Measurements of first-phase insulin release, insulin sensitivity, glucose effectiveness, and the constant for glucose disappearance (Kg) were measured at baseline, at the end of 2 weeks of therapy, and after subjects had been off therapy for at least 2 weeks. Nicotinamide administration caused a 23.6% decrease in insulin sensitivity (P = 0.02). This decrease was associated with a fall in Kg despite increased insulin secretion. Our data suggest that the use of nicotinamide in subjects who are at risk of developing IDDM may be complicated by the drug's effects on insulin sensitivity. By inducing insulin resistance, a therapeutic effect of nicotinamide on the diabetes disease process may be missed, and the interpretation of insulin secretion measurements that are obtained during the intervention trials using nicotinamide may be complicated by the changes in insulin secretion that are caused by the increased insulin resistance. Therefore, we strongly support the recommendation that at least one subgroup of subjects enrolled in clinical trials to prevent IDDM have regular measurements of both insulin sensitivity and insulin secretion performed. This subgroup should be randomly assigned and large enough for statistical analysis to interpret properly the changes in insulin secretion that may occur.


Abeta-afferents activate neurokinin-1 receptor in dorsal horn neurons after nerve injury.
We provide new evidence demonstrating that peripheral nerve injury produces profound alterations in synaptic input to dorsal horn neurons mediated by non-nociceptive sensory neurons, and activation of neurokinin-1 receptor may be involved in the enhanced synaptic response and thus contribute to the tactile allodynia. Our results show that Abeta-fiber-evoked field potential significantly increased in the first postoperative week and decreased thereafter while maximal mechanical allodynia was exhibited. The neurokinin-1 receptor antagonist L703,606 significantly reduced Abeta-fiber-evoked field potential in nerve-injured but not in sham-operated animals. The non-N-methyl-D-aspartate receptor antagonist CNQX inhibited Abeta-fiber-evoked field potential in both nerve-injured and sham-operated rats, while the N-methyl-D-aspartate receptor antagonist MK-801 did not affect Abeta-fiber-evoked field potential in either CCI or sham-operated animals.


Machine wanting.
Wants, preferences, and cares are physical things or events, not ideas or propositions, and therefore no chain of pure logic can conclude with a want, preference, or care. It follows that no pure-logic machine will ever want, prefer, or care. And its behavior will never be driven in the way that deliberate human behavior is driven, in other words, it will not be motivated or goal directed. Therefore, if we want to simulate human-style interactions with the world, we will need to first understand the physical structure of goal-directed systems. I argue that all such systems share a common nested structure, consisting of a smaller entity that moves within and is driven by a larger field that contains it. In such systems, the smaller contained entity is directed by the field, but also moves to some degree independently of it, allowing the entity to deviate and return, to show the plasticity and persistence that is characteristic of goal direction. If all this is right, then human want-driven behavior probably involves a behavior-generating mechanism that is contained within a neural field of some kind. In principle, for goal directedness generally, the containment can be virtual, raising the possibility that want-driven behavior could be simulated in standard computational systems. But there are also reasons to believe that goal-direction works better when containment is also physical, suggesting that a new kind of hardware may be necessary.


BeadCons: detection of nucleic acid sequences by flow cytometry.
Molecular beacons are single-stranded nucleic acid structures with a terminal fluorophore and a distal, terminal quencher. These molecules are typically used in real-time PCR assays, but have also been conjugated with solid matrices. This unit describes protocols related to molecular beacon-conjugated beads (BeadCons), whose specific hybridization with complementary target sequences can be resolved by cytometry. Assay sensitivity is achieved through the concentration of fluorescence signal on discrete particles. By using molecular beacons with different fluorophores and microspheres of different sizes, it is possible to construct a fluid array system with each bead corresponding to a specific target nucleic acid. Methods are presented for the design, construction, and use of BeadCons for the specific, multiplexed detection of unlabeled nucleic acids in solution. The use of bead-based detection methods will likely lead to the design of new multiplex molecular diagnostic tools.


The fatty acid amide hydrolase in lymphocytes from sedentary and active subjects.
Endocannabinoids (eCB) and interleukin 6 (IL-6) levels change during physical activity, thus suggesting their involvement in the modulation of exercise-related processes like inflammation and energy homeostasis. To investigate whether lifestyle might affect the activity of the eCB-degrading enzyme fatty acid amide hydrolase (FAAH), active and sedentary subjects were enrolled. Plasma IL-6 levels and lymphocyte FAAH activity of eight physically active male subjects (mean ± SEM; age = 39.3 ± 2.9 yr, body mass index = 21.1 ± 0.4 kg·m), usually practicing aerobic exercise (8.1 ± 1.2 h·wk), and eight sedentary subjects (38.8 ± 3.7 yr, body mass index = 23.1 ± 0.8 kg·m) were measured. Also, in vitro effect of IL-6 was tested on FAAH expression and activity and on FAAH promoter activity in lymphocytes from sedentary subjects. Under resting conditions (at least 12 h from the last exercise), the active group showed plasma IL-6 levels (2.74 ± 0.73 pg·mL) and lymphocyte FAAH activity (215.7 ± 38.5 pmol·min·mg protein) significantly higher than those measured in the sedentary group (0.20 ± 0.02 pg·mL, and 42.0 ± 4.2 pmol·min·mg protein). Increased IL-6 levels paralleled increased FAAH activity, and consistently, the in vitro treatment of lymphocytes from sedentary individuals with 10 ng·mL IL-6 for 48 h significantly increased FAAH expression and activity. Transient transfection experiments showed that IL-6 induced the expression of a reporter gene under the control of a cAMP response element-like region in the human FAAH promoter. A mutation in the same element abolished IL-6 up-regulation, demonstrating that this cytokine regulates FAAH activity at the transcriptional level. IL-6 leads to activation of the FAAH promoter, thus enhancing FAAH activity that modulates the eCB tone in physically active people.


The Hypervariable Tpr Multigene Family of Theileria Parasites, Defined by a Conserved, Membrane-Associated, C-Terminal Domain, Includes Several Copies with Defined Orthology Between Species.
Multigene families often play an important role in host-parasite interactions. One of the largest multigene families in Theileria parva, the causative agent of East Coast fever, is the T. parva repeat (Tpr) gene family. The function of the putative Tpr proteins remains unknown. The initial publication of the T. parva reference genome identified 39 Tpr family open reading frames (ORFs) sharing a conserved C-terminal domain. Twenty-eight of these are clustered in a central region of chromosome 3, termed the "Tpr locus", while others are dispersed throughout all four nuclear chromosomes. The Tpr locus contains three of the four assembly gaps remaining in the genome, suggesting the presence of additional, as yet uncharacterized, Tpr gene copies. Here, we describe the use of long-read sequencing to attempt to close the gaps in the reference assembly of T. parva (located among multigene families clusters), characterize the full complement of Tpr family ORFs in the T. parva reference genome, and evaluate their evolutionary relationship with Tpr homologs in other Theileria species. We identify three new Tpr family genes in the T. parva reference genome and show that sequence similarity among paralogs in the Tpr locus is significantly higher than between genes outside the Tpr locus. We also identify sequences homologous to the conserved C-terminal domain in five additional Theileria species. Using these sequences, we show that the evolution of this gene family involves conservation of a few orthologs across species, combined with gene gains/losses, and species-specific expansions.


Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany.
Previous studies of cognition enhancers have mainly focused on insufficiently defined groups of cognition disorders, e.g., "cerebral insufficiency". With regard to the various biological changes in senile dementia of Alzheimer's type (SDAT) and in vascular dementia (VD), which together make up the great majority of senile dementias, many authors have encouraged different studies of these types of dementias, especially since both can be diagnosed clinically with satisfying certainty. Since primary care physicians treat the majority of elderly and demented patients, they have their own experience with cognition enhancers. We were therefore interested to know, how far these physicians differ in their treatment of SDAT and VD. We performed a representative survey (response rate 83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A written case vignette described a 70-year-old widow with moderate dementia and vascular risk factors which are easily treated with drugs. Two versions were randomly assigned, in which (version A) either a "typical" VD history or a typical SDAT history (version B) were described. After perusal, the physician was asked whether and which drugs he would choose to treat the cognitive disorders in this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by 29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of dementia was concerned, significant differences were found only for co-dergocrine, which was preferred in SDAT. The following inter-group trends were observed: family physicians considered ginkgo biloba more often than nimodipine or co-dergocrine. The results show the apparent importance of cost-and safety aspects, while the type of dementia has hardly any impact. The latter impression corresponds to the results of drug trials demonstrating no different efficacy. In our opinion, aspirin was not sufficiently taken into consideration.


Validity of body-worn sensor acceleration metrics to index upper extremity function in hemiparetic stroke.
Accelerometers have been used to capture real-world use of the paretic upper extremity in people with stroke. It may be possible to characterize different aspects of the recorded acceleration to gain insight about movement capabilities during task-specific behavior. These measures may be of value for guiding rehabilitation. We undertook a study to identify the acceleration characteristics that have a stable association with upper extremity function and sensitivity to within-participant fluctuations in function over multiple sessions of task-specific training. Twenty-seven adults 6 months or more poststroke with upper extremity paresis participated. Signals from wrist-worn accelerometers were sampled at 30 Hz during 7 sessions of task-specific training. Paretic upper extremity function was evaluated with the Action Research Arm Test. We used Spearman correlations to examine within-session associations between acceleration metrics and Action Research Arm Test performance. A mixed model was used to determine which metrics were sensitive to within-participant fluctuations in upper extremity function across the 7 training sessions. Upper extremity function correlated with bilateral acceleration variability and use ratio during 5 and 6 sessions, respectively. Time accelerating between 76% and 100% of peak acceleration correlated with function in 6 sessions. Variability of the paretic upper extremity acceleration and the ratio of acceleration variability between upper extremities were associated with function during all 7 sessions. Variability in both the acceleration of the paretic upper extremity, and acceleration of the paretic and nonparetic extremities combined were sensitive to within-participant fluctuations in function across training sessions. Multiple features of the acceleration profile track with upper extremity function within and across sessions of task-specific training. It may be possible to monitor these features with accelerometers to index upper extremity function outside of clinical settings.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A91).


Psoriasis: cardiovascular risk factors and other disease comorbidities.
The risk factors of cardiovascular disease and other disease comorbidities appear to be more common in patients with psoriasis compared with the general population. To support this concept, the association between psoriasis and cardiovascular disease and other comorbidities was analyzed using data collected from 40 730 patients in the National Health and Wellness Survey (NHWS) during May and June 2004. A case-control study was conducted with data from 1127 patients with psoriasis and a matched cohort of nonpsoriasis patients. Psoriasis patients were significantly more likely to have cardiovascular comorbidities, including hypertension, hypercholesterolemia, and diabetes, compared with nonpsoriasis patients. Other comorbidities significantly associated with psoriasis were arthritis, depression, sleep disorder/insomnia, chronic obstructive pulmonary disease, and gastroesophageal reflux disease. Responses to this large survey confirm that patients with psoriasis have a higher rate of cardiovascular risk factors and other comorbidities compared with patients without psoriasis.


Subjective and physiological effects of intravenous nicotine and cocaine in cigarette smoking cocaine abusers.
The subjective and physiological effects of intravenously administered cocaine and nicotine were compared in 10 cigarette-smoking cocaine abusers. Subjects abstained from smoking at least 8 h before each session. Under double blind conditions, subjects received placebo, cocaine (10, 20, and 40 mg/70 mg), or nicotine (0.75, 1.5, 3.0 mg/70 kg) in mixed order. Physiological and subjective data were collected before and repeatedly after each intravenous drug administration. Subjects also completed a drug versus money multiple-choice procedure in which they chose between that day's drug and 44 monetary values. Both drugs increased blood pressure and heart rate and decreased skin temperature. Nicotine showed a more rapid onset of subjective effects than cocaine. Overall, although both cocaine and nicotine increased subjective ratings of "drug effect", "rush", "good effects", "liking", "high", and "stimulated", only nicotine increased ratings of "bad effects" and "jittery". Although the highest nicotine dose produced greater effects than the highest cocaine dose on most subjective measures, the highest cocaine dose produced somewhat greater ratings of drug liking. At doses that produced comparable ratings of drug effect (40 mg/70 kg cocaine versus 1.5 mg/70 kg nicotine), cocaine produced significantly greater good effects, whereas nicotine produced greater bad effects. All three cocaine doses and the intermediate and high nicotine doses were frequently categorized as producing effects similar to those of cocaine or amphetamine. The drug versus money measure showed that the highest cocaine dose was worth twice as much as the highest nicotine dose. Thus, intravenous cocaine and nicotine can be differentiated by their subjective and reinforcing effects.


Fracture resistance of endodontically treated premolars with fibre-reinforced composite restorations.
This study investigated the fracture resistance and failure mode of endodontically treated premolars restored with a glass fibre-reinforced composite resin. Endodontically treated maxillary premolars were divided in 4 groups: group O: occlusal access opening restored with direct composite; group O+: as group O but with fibre reinforcement; group MOD: occlusal access opening and mesio-distal (MOD) cavity restored with direct composite; group MOD+: as group MOD but with additional fibre reinforcement. Pairwise comparisons of the fracture force among all groups was performed (95% confidence level). Fractures were classified in 4 groups depending on the type of fracture. Group O was the strongest (452.7N) and group MOD the weakest (292.4N). Fracture resistance was significantly different among all groups, except between groups O+ and MOD+. The majority of the unreinforced teeth displayed unfavourable fractures, while the reinforced teeth displayed more favourable fractures. The incorporation of glass fibre weakened endodontically treated but otherwise intact premolars; premolars with MOD restorations were stronger if reinforced with fibres. Fibre reinforcement led to more favourable fractures.


COVID-19 in Kidney Transplant Recipients With Diabetes Mellitus: A Propensity Score Matching Analysis.
Kidney transplant recipients present higher rates of pre-existing comorbidities, in particular diabetes mellitus (DM), hypertension, and cardiac disease. We aimed to verify the main risk factors related to DM that contribute to COVID-19 progression and mortality in a kidney transplant setting. From March to August 2020, we evaluated 300 kidney transplant recipients affected by COVID-19. We used propensity score matching (PSM) to estimate the impact of DM on COVID-19. After matching, all baseline characteristics were well balanced between those with and without DM (n = 100 in each group). Case fatality rate, the requirement of invasive mechanical ventilation (IMV), and acute kidney injury (AKI) were associated with previous fasting blood glucose, and C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels on admission. These findings were similar in kidney transplant patients with and without DM. Glycemia on admission and estimated glomerular filtration rate (eGFR) either on admission or basal correlated to the need of IMV and development of AKI, respectively. Poor glycaemic control, eGFR, markers of inflammation (CRP) and tissue damage (LDH) were indicative of COVID-19 burden in kidney transplant recipients and may be useful tools for risk-stratifying this population, independently of the DM status, during the pandemic.


Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease.
Iron-sulfur (Fe-S) proteins contain prosthetic groups consisting of two or more iron atoms bridged by sulfur ligands, which facilitate multiple functions, including redox activity, enzymatic function, and maintenance of structural integrity. More than 20 proteins are involved in the biosynthesis of iron-sulfur clusters in eukaryotes. Defective Fe-S cluster synthesis not only affects activities of many iron-sulfur enzymes, such as aconitase and succinate dehydrogenase, but also alters the regulation of cellular iron homeostasis, causing both mitochondrial iron overload and cytosolic iron deficiency. In this work, we review human Fe-S cluster biogenesis and human diseases that are caused by defective Fe-S cluster biogenesis. Fe-S cluster biogenesis takes place essentially in every tissue of humans, and products of human disease genes, including frataxin, GLRX5, ISCU, and ABCB7, have important roles in the process. However, the human diseases, Friedreich ataxia, glutaredoxin 5-deficient sideroblastic anemia, ISCU myopathy, and ABCB7 sideroblastic anemia/ataxia syndrome, affect specific tissues, while sparing others. Here we discuss the phenotypes caused by mutations in these different disease genes, and we compare the underlying pathophysiology and discuss the possible explanations for tissue-specific pathology in these diseases caused by defective Fe-S cluster biogenesis.


Vector quantization for entropy coding of image subbands.
Vector quantization for entropy coding of image subbands is investigated. Rate distortion curves are computed with mean square error as a distortion criterion. The authors show that full-search entropy-constrained vector quantization of image subbands results in the best performance, but is computationally expensive. Lattice quantizers yield a coding efficiency almost indistinguishable from optimum full-search entropy-constrained vector quantization. Orthogonal lattice quantizers were found to perform almost as well as lattice quantizers derived from dense sphere packings. An optimum bit allocation rule based on a Lagrange multiplier formulation is applied to subband coding. Coding results are shown for a still image.


Quantitative electroencephalography during rapid eye movement (REM) and non-REM sleep in combat-exposed veterans with and without post-traumatic stress disorder.
Sleep disturbances are a hallmark feature of post-traumatic stress disorder (PTSD), and associated with poor clinical outcomes. Few studies have examined sleep quantitative electroencephalography (qEEG), a technique able to detect subtle differences that polysomnography does not capture. We hypothesized that greater high-frequency qEEG would reflect 'hyperarousal' in combat veterans with PTSD (n = 16) compared to veterans without PTSD (n = 13). EEG power in traditional EEG frequency bands was computed for artifact-free sleep epochs across an entire night. Correlations were performed between qEEG and ratings of PTSD symptoms and combat exposure. The groups did not differ significantly in whole-night qEEG measures for either rapid eye movement (REM) or non-REM (NREM) sleep. Non-significant medium effect sizes suggest less REM beta (opposite to our hypothesis), less REM and NREM sigma and more NREM gamma in combat veterans with PTSD. Positive correlations were found between combat exposure and NREM beta (PTSD group only), and REM and NREM sigma (non-PTSD group only). Results did not support global hyperarousal in PTSD as indexed by increased beta qEEG activity. The correlation of sigma activity with combat exposure in those without PTSD and the non-significant trend towards less sigma activity during both REM and NREM sleep in combat veterans with PTSD suggests that differential information processing during sleep may characterize combat-exposed military veterans with and without PTSD.


Molecular and morphological differentiation of two similar species of Accacoeliidae (Digenea): Accacladocoelium macrocotyle and A. nigroflavum from sunfish, Mola mola.
In a study of 106 sunfish, Mola mola (L.), from Mediterranean waters, 2,731 worms, belonging to 2 congeneric species of accacoeliids, Accacladocoelium macrocotyle (Diesing, 1858) Robinson, 1934 and Accacladocoelium nigroflavum (Rudolphi, 1819) Robinson, 1934 , were collected from the digestive system. It is often difficult to differentiate between these 2 species as they are sympatric and very similar; in fact, according to previous descriptions, the extent of the vitellarium is the only interspecific difference, described as extending posteriorly to the ovary in A. macrocotyle and as anterior to the anterior testis in A. nigroflavum. However, this diagnostic trait is not always valid; moreover, it is often indistinguishable because it is masked by the uterine eggs. Here, the morphology of new specimens of both species has been studied in detail and combined with molecular analysis. This study shows that the extension of the vitellarium is very similar in both species, but the degree of ramification differs. Furthermore, although the morphological differences are very slight, both species seemed genetically different: intraspecific differences ranged between 0.8 and 1.5% in internal transcribed spacer (ITS)-2 rRNA gene (ITS2) and between 0.5 and 1.6% in cytochrome c oxidase subunit 1 (COI) and interspecific differences ranged between 2 and 3.2% in ITS2 and between 9.6 and 10.6% in COI. In addition, we observed previously undescribed morphological differences, which help to differentiate these 2 species: the oral sucker is relatively smaller in A. nigroflavum than in A. macrocotyle and the ovary is usually relatively longer in A. nigroflavum than in A. macrocotyle.


Fall risk and function in older women after gynecologic surgery.
To examine change in balance-related fall risk and daily functional abilities in the first 2 post-operative weeks and up to 6 weeks after gynecologic surgery. Prospective cohort study in gynecologic surgery patients age 65 and older. Balance confidence (Activities-specific Balance Confidence Scale) and functional status (basic and instrumental activities of daily living) were recorded pre- and post-operatively daily for 1 week and twice the second week. Physical performance balance and functional mobility were measured pre- and 1 week post-operatively using the Tinetti Fall Risk Scale, Timed Up and Go, and 6-Minute Walk test. Measures were repeated 6 weeks after surgery. Non-parametric tests for paired data were used comparing scores baseline to post-operative (POD) 7 and to POD 42. Median age was 72 years (range 65-88). Fall risk was elevated during the first 2 post-operative weeks, greatest on the median discharge day, POD 2 (p<0.01). Balance performance and functional mobility at 1 week were significantly lower than baseline (p<0.01). Functional abilities declined, including new dependence in medication management at home in 22% of these independent and cognitively intact women. After gynecologic surgery, older women's fall risk is highest on POD 2 and remains elevated from baseline for 2 weeks. Functional limitations in the early home recovery period include the anticipated (bathing, cooking, etc.) and some unanticipated (medication management) ones. This information may help with post-operative discharge planning.


The cost of expression of Escherichia coli lac operon proteins is in the process, not in the products.
Transcriptional regulatory networks allow bacteria to express proteins only when they are needed. Adaptive hypotheses explaining the evolution of regulatory networks assume that unneeded expression is costly and therefore decreases fitness, but the proximate cause of this cost is not clear. We show that the cost in fitness to Escherichia coli strains constitutively expressing the lactose operon when lactose is absent is associated with the process of making the lac gene products, i.e., associated with the acts of transcription and/or translation. These results reject the hypotheses that regulation exists to prevent the waste of amino acids in useless protein or the detrimental activity of unnecessary proteins. While the cost of the process of protein expression occurs in all of the environments that we tested, the expression of the lactose permease could be costly or beneficial, depending on the environment. Our results identify the basis of a single selective pressure likely acting across the entire E. coli transcriptome.


[Advances in understanding of the virulence mechanism of Mycobacterium tuberculosis].
Mycobacterium tuberculosis (MTB) is an intracellular pathogen that has evolved strategies to enable growth in macrophages. The bacterium is able to inhibit fusion of phagosomes with lysosomes through secretion of some bacterial components and modulation of host intracellular signaling pathways. Furthermore, it has been shown that phagositosed MTB is killed within macrophages after treatment with IFN-gamma in vitro. However, virulent MTB is capable of surviving in macrophages in vivo and persists in host even after acquired immunity has developed. These data suggest that MTB has developed a sophisticated immune evasion mechanism. In this issue, the strategies of MTB for intracellular survival and immune evasion, which have been unraveled so far, are shown and the mechanisms are discussed.


Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind?
To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system. We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time. In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy. Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible.


Associations between DNA sequence variation and variation in expression of the Adh gene in natural populations of Drosophila melanogaster.
A large part of the genetic variation in alcohol dehydrogenase (ADH) activity level in natural populations of Drosophila melanogaster is associated with segregation of an amino acid replacement polymorphism at nucleotide 1490, which generates a difference in electrophoretic mobility. Part of the allozymic difference in activity level is due to a catalytic efficiency difference, which is also caused by the amino acid replacement, and part is due to a difference in the concentration of ADH protein. A previous site-directed in vitro mutagenesis experiment clearly demonstrated that the amino acid replacement has no effect on the concentration of ADH protein, nor does a strongly associated silent polymorphism at nucleotide 1443. Here we analyze associations between polymorphisms within the Adh gene and variation in ADH protein level for a number of chromosomes derived from natural populations. A sequence length polymorphism within the first intron of the distal (adult) transcript, 1, is in strong linkage disequilibrium with the amino acid replacement. Among a sample of 46 isochromosomal lines analyzed, all but one of the 14 Fast lines have 1 and all but one of the 32 Slow lines lack 1. The exceptional Fast line has an unusually low level of ADH protein (typical of Slow lines) and the exceptional Slow line has an unusually high level (typical of Fast lines). These results suggest that the 1 polymorphism may be responsible for the average difference in ADH protein between the allozymic classes. A previous experiment localized the effect on ADH protein to a 2.3-kb restriction fragment. DNA sequences of this fragment from several alleles of each allozymic type indicate that no other polymorphisms within this region are as closely associated with the ADH protein level difference as the 1 polymorphism.


HRAS mutants identified in Costello syndrome patients can induce cellular senescence: possible implications for the pathogenesis of Costello syndrome.
Costello syndrome (CS) is a congenital disease that is characterized by a distinctive facial appearance, failure to thrive, mental retardation and cardiomyopathy. In 2005, we discovered that heterozygous germline mutations in HRAS caused CS. Several studies have shown that CS-associated HRAS mutations are clustered in codons 12 and 13, and mutations in other codons have also been identified. However, a comprehensive comparison of the substitutions identified in patients with CS has not been conducted. In the current study, we identified four mutations (p.G12S, p.G12A, p.G12C and p.G12D) in 21 patients and analyzed the associated clinical manifestations of CS in these individuals. To examine functional differences among the identified mutations, we characterized a total of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13, p.K117R and p.A146T. The p.A146T mutant demonstrated the weakest Raf-binding activity, and the p.K117R and p.A146T mutants had weaker effects on downstream c-Jun N-terminal kinase signaling than did codon 12 or 13 mutants. We demonstrated that these mutant HRAS proteins induced senescence when overexpressed in human fibroblasts. Oncogene-induced senescence is a cellular reaction that controls cell proliferation in response to oncogenic mutation and it has been considered one of the tumor suppression mechanisms in vivo. Our findings suggest that the HRAS mutations identified in CS are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS.


In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate.
In situ formation of nanocrystals and dissolution profiles of fenofibrate (FFB) from a self-microemulsifying drug delivery system (SMEDDS) were characterized. SMEDDS formulated with Myritol and surfactant mixture (Smix) of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and either Tween 20 (A, C, E, G, M, S, N, T, O) or Tween 80 (B, D, F, H, P, U, Q, V, R) at various oil/Smix ratios (Group I: A and B of 0.42, C and D of 0.25, E and F of 0.11; Group II: G and H of 1.38, M and P of 1.11, S and U of 0.9, N and Q of 0.73, T and V of 0.58, and O and R of 0.46) and water contents (1: 9.5%, 2: 5.0%, 3: 0.0%, G-V: 4.5%). Their dissolutions were conducted at different rotation speeds. Two optimal SMEDDSs containing Tween 80(B2) or a higher oil/Smix ratio(Q) and B2(solution) were selected for pharmacokinetic study. FFB particles formed within the nanosize range from Group I gradually increased with time but decreased with increasing stirring rates. However, the mean size of FFB formed by B series was as low as 200 nm, which was smaller than that of A series at three stirring rates. The release rate from both groups obviously increased with increasing stirring rate. However, incomplete release was observed for S and N in Tween 20 series, whereas a faster release rate and complete release were observed for Tween 80 series with an insignificant difference among them. Results of pharmacokinetic study demonstrated that the highest-ranked area under the curve and Cmax values were for Q(SMEDDS) and B2(solution), respectively. The relative bioavailability of Q(SMEDDS) with respect to Tricor was enhanced by about 1.14-1.22-fold. SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB.


Diagnosis and management of pulmonary arterial hypertension: Implications for respiratory care.
Pulmonary arterial hypertension (PAH) is a pathological condition of the small pulmonary arteries. PAH is characterized histopathologically by vasoconstriction, vascular proliferation, in situ thrombosis, and remodeling of all 3 levels of the vascular walls. These pathologic changes result in progressive increases in the mean pulmonary-artery pressure and pulmonary vascular resistance, which, if untreated, leads to right-ventricular failure and death. PAH can be associated with multiple conditions or risk factors (eg, collagen vascular diseases, liver disease, human immunodeficiency virus, congenital heart disease, or ingestion of certain medications or toxins) or it can be idiopathic. Up to 10% of the idiopathic cases are familial. Regardless of the etiology, the clinical presentation, histopathologic lesions, and response to therapy are all similar. Early in the disease process, the signs and symptoms of PAH are often subtle and nonspecific, making diagnosis challenging. Patients most often present with progressively worsening dyspnea and fatigue. An extensive evaluation is indicated to diagnose PAH, decipher its etiology, and determine long-term treatment goals. Transthoracic echocardiogram is an excellent screening tool to evaluate PAH, but every patient requires a right-side heart catheterization to help stage the disease and guide therapy. Prior to a decade ago, clinicians were only able to offer symptomatic therapy to this challenging group of patients. Earlier diagnosis, rapidly advancing understanding of the pathogenesis, and an increasing number of treatment options have changed the course of PAH, which was once thought to be invariably fatal.


Dog noise as a risk factor for hearing loss among police dog handlers.
To determine the sources of noise exposure among police dog handlers and to examine whether these levels might lead to noise-induced hearing loss. We conducted a cross-sectional study at four Royal Air Force bases using a noise survey, a postal questionnaire and medical record review. The noise survey was conducted following task analysis. We surveyed police dog handlers and a comparison group of police who had never been dog handlers, using a postal questionnaire on noise exposures and confounders. Audiometric and otological data were extracted from medical records. The noise survey revealed significant exposures due to dogs, travelling in vans and aircraft noise during foot patrol. The overall response rate to the questionnaire was 56% (29 police dog handlers, 24 police officers). Five subjects (9.4%) had age-corrected hearing loss exceeding 10 dB, averaged over the 4 and 6 kHz frequencies, affecting the left ear only, but there were no differences between dog handlers and controls. Although the measured noise exposures of police dog handlers did not exceed current legal limits, the noise levels at times are such that the proposed Physical Agents (Noise) Directive has implications for employers who use dogs for security purposes.


Efficient synthesis of ureas by direct palladium-catalyzed oxidative carbonylation of amines.
A general synthesis of symmetrically disubstituted ureas and trisubstituted ureas by direct Pd-catalyzed oxidative carbonylation of primary amines or of a mixture of a primary and a secondary amine, respectively, with unprecedented catalytic efficiencies for this kind of process, is reported. Reactions are carried out at 90-100 degrees C in DME as the solvent in the presence of PdI(2) in conjunction with an excess of KI as the catalytic system and under 20 atm of a 4:1 mixture of CO and air. In some cases, working in the presence of an excess of CO(2) (40 atm) in addition to CO and air (60 atm total) had a beneficial effect on substrate reactivity and product yield. Cyclic five-membered and six-membered ureas were easily formed from primary diamines. The methodology has been successfully applied to the synthesis of pharmacologically active ureas, such as those deriving from alpha-amino esters or urea NPY5RA-972, a potent antagonist of the neuropeptide Y5 receptor.


[Genome-wide association studies: methodology and interpretation for clinicians].
Genome-wide association studies (GWAS) are performed to find associations between genetic variants (i.e. single-nucleotide polymorphisms) and diseases. This review describes the basic principles of GWAS. To date, GWAS have identified thousands of genetic variants associated with complex diseases and biological characteristics such as LDL cholesterol levels. GWAS can provide important insights into the underlying mechanisms of complex diseases and biological characteristics, thereby aiding the development of biomarkers and potentially pinpointing novel drug targets.


A Novel 3-O-rhamnoside: 2″-O-xylosyltransferase Responsible for Terminal Modification of Prenylflavonol Glycosides in Epimedium pubescens Maxim.
Prenylated flavonol glycosides in Epimedium plants, as key medicinal components, are known to have great pharmaceutical activities for human health. Among the main prenylated flavonol glycosides, the modification mechanism of different sugar moieties is still not well understood. In the current study, a novel prenylated flavonol rhamnoside xylosyltransferase gene (EpF3R2″XylT) was cloned from E. pubescens, and the enzymatic activity of its decoding proteins was examined in vitro with different prenylated flavonol rhamnoside substrates and different 3-O-monosaccharide moieties. Furthermore, the functional and structural domains of EpF3R2″XylT were analyzed by bioinformatic approaches and 3-D protein structure remodeling. In summary, EpF3R2″XylT was shown to cluster with GGT (glycosyltransferase that glycosylates sugar moieties of glycosides) through phylogenetic analysis. In enzymatic analysis, EpF3R2″XylT was proven to transfer xylose moiety from UDP-xylose to prenylated flavonol rhamnoside at the 2″-OH position of rhamnose. The analysis of enzymatic kinetics showed that EpF3R2″XylT had the highest substrate affinity toward icariin with the lowest Km value of 75.96 ± 11.91 mM. Transient expression of EpF3R2″XylT in tobacco leaf showed functional production of EpF3R2″XylT proteins in planta. EpF3R2″XylT was preferably expressed in the leaves of E. pubescens, which is consistent with the accumulation levels of major prenylflavonol 3-O-triglycoside. The discovery of EpF3R2″XylT will provide an economical and efficient alternative way to produce prenylated flavonol trisaccharides through the biosynthetic approach.


Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis?
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women, potentially due to ineffectiveness of screening tests for early detection. Patients typically present with advanced disease at diagnosis, whereas, up to 80% relapse and the estimated median progression-free survival (PFS) is approximately 12-18 months. Increased knowledge on the molecular biology of EOC resulted in the development of several targeted therapies, including poly(ADP-ribose) polymerase (PARP) inhibitors. These agents have changed the therapeutic approach of the EOC and exploit homologous recombination (HR) deficiency through synthetic lethality, especially in breast cancer genes 1 and 2 (BRCA1/2) mutation carriers. Furthermore, BRCA wild-type patients with other defects in the HR repair pathway, or those with platinum-resistant tumors may obtain benefit from this treatment. While PARP inhibitors as a class display many similarities, several differences in structure can translate into differences in tolerability and antitumor activity. Currently, olaparib, rucaparib, and niraparib have been approved by Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) for the treatment of EOC, while veliparib is in the late stage of clinical development. Finally, since October 2018 talazoparib is FDA and EMA approved for BRCA carriers with metastatic breast cancers. In this article, we explore the mechanisms of DNA repair, synthetic lethality, efficiency of PARP inhibition, and provide an overview of early and ongoing clinical investigations of the novel PARP inhibitors veliparib and talazoparib.


Type of tunable guided-mode resonance filter based on electro-optic characteristic of polymer-dispersed liquid crystal.
A narrowband guided-mode resonance filter (GMRF) incorporating polymer-dispersed liquid crystal (PDLC) is designed. Simulating the characteristics of the filter with rigorous coupled-wave analysis, we find that the resonance wavelength of the new kind of GMRF can be tuned from 672.4 to 698.4 nm by varying the refractive index of the PDLC layer with the applied voltage. Furthermore, the resonance wavelengths vary in a linear fashion with respect to the refractive index of the PDLC layer. Therefore, the desired resonance wavelength can be conveniently selected and tuned in a tuning range of 26 nm by using the applied voltage.


Regional blood flow and water content of the obstructed small intestine.
The effects of small-bowel obstruction on the regional distribution of blood flow and water content were studied in a new chronic dog model. Nonstrangulative obstruction was induced 40 cm proximal to the canine ileocolic valve. Blood flow was measured with 15-micron microspheres and hemodynamic and respiratory values were recorded before (experimental phase I) and five days after (experimental phase II) the induction of the obstruction. Two separate control groups of dogs were studied: baseline controls and sham-operative groups (phases I and II). Hemodynamic and respiratory values were stable in both phases in all groups. A comparison of sham phase-II data with the experimental phase-II data in the 120-cm segment of bowel proximal to the site of obstruction showed an 85% increase in blood flow (range, 49% to 106%); for the 280 cm of bowel proximal to the site of obstruction, there was a 6% increase in water content (range, 5% to 9%), and a 39% decrease in dry bowel weight (range, 34% to 46%). These findings help illustrate the pathophysiologic characteristics of microvascular changes in bowel obstruction, which are likely to have particular clinical significance for patients with cardiopulmonary diseases.


Identifying the Distinct Cognitive Phenotypes in Multiple Sclerosis.
Cognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking. To identify cognitive phenotypes in a clinical cohort of patients with MS and to characterize their clinical and magnetic resonance imaging (MRI) features. This multicenter cross-sectional study consecutively screened clinically stable patients with MS and healthy control individuals at 8 MS centers in Italy from January 1, 2010, to October 31, 2019. Patients with MS and healthy control individuals who were not using psychoactive drugs and had no history of other neurological or medical disorders, learning disability, severe head trauma, and alcohol or drug abuse were enrolled. Participants underwent a neurological examination and a cognitive evaluation with the Rao Brief Repeatable Battery and Stroop Color and Word Test. A subgroup of participants also underwent a brain MRI examination. Latent profile analysis was used on cognitive test z scores to identify cognitive phenotypes. Linear regression and mixed-effects models were used to define clinical and MRI features of each phenotype. A total of 1212 patients with MS (mean [SD] age, 41.1 [11.1] years; 784 women [64.7%]) and 196 healthy control individuals (mean [SD] age, 40.4 [8.6] years; 130 women [66.3%]) were analyzed in this study. Five cognitive phenotypes were identified: preserved cognition (n = 235 patients [19.4%]), mild-verbal memory/semantic fluency (n = 362 patients [29.9%]), mild-multidomain (n = 236 patients [19.5%]), severe-executive/attention (n = 167 patients [13.8%]), and severe-multidomain (n = 212 patients [17.5%]) involvement. Patients with preserved cognition and mild-verbal memory/semantic fluency were younger (mean [SD] age, 36.5 [9.8] years and 38.2 [11.1] years) and had shorter disease duration (mean [SD] 8.0 [7.3] years and 8.3 [7.6] years) compared with patients with mild-multidomain (mean [SD] age, 42.6 [11.2] years; mean [SD] disease duration, 12.8 [9.6] years; P < .001), severe-executive/attention (mean [SD] age, 42.9 [11.7] years; mean [SD] disease duration, 12.2 [9.5] years; P < .001), and severe-multidomain (mean [SD] age, 44.0 [11.0] years; mean [SD] disease duration, 13.3 [10.2] years; P < .001) phenotypes. Severe cognitive phenotypes prevailed in patients with progressive MS. At MRI evaluation, compared with those with preserved cognition, patients with mild-verbal memory/semantic fluency exhibited decreased mean (SE) hippocampal volume (5.42 [0.68] mL vs 5.13 [0.68] mL; P = .04), patients with the mild-multidomain phenotype had decreased mean (SE) cortical gray matter volume (687.69 [35.40] mL vs 662.59 [35.48] mL; P = .02), patients with severe-executive/attention had higher mean (SE) T2-hyperintense lesion volume (51.33 [31.15] mL vs 99.69 [34.07] mL; P = .04), and patients with the severe-multidomain phenotype had extensive brain damage, with decreased volume in all the brain structures explored, except for nucleus pallidus, amygdala and caudate nucleus. This study found that by defining homogeneous and clinically meaningful phenotypes, the limitations of the traditional dichotomous classification in MS can be overcome. These phenotypes can represent a more meaningful measure of the cognitive status of patients with MS and can help define clinical disability, support clinicians in treatment choices, and tailor cognitive rehabilitation strategies.


The phenotype and neural correlates of language in autism: an integrative review.
Although impaired communication is one of the defining criteria in autism, linguistic functioning is highly variable among people with this disorder. Accumulating evidence shows that language impairments in autism are more extensive than commonly assumed and described by formal diagnostic criteria and are apparent at various levels. Phenotypically, most people with autism have semantic, syntactic and pragmatic deficits, a smaller number are known to have phonological deficits. Neurophysiologically, abnormal processing of low-level linguistic information points to perceptual difficulties. Also, abnormal high-level linguistic processing of the frontal and temporal language association cortices indicates more self-reliant and less connected neural subsystems. Early sensory impairments and subsequent atypical neural connectivity are likely to play a part in abnormal language acquisition in autism. This paper aims to review the available data on the phenotype of language in autism as well as a number of structural, electrophysiological and functional brain-imaging studies to provide a more integrated view of the linguistic phenotype and its underlying neural deficits, and to provide new directions for research and therapeutic and experimental applications.


Ultrasensitive and Label-Free Detection of the Measles Virus Using an N-Heterocyclic Carbene-Based Electrochemical Biosensor.
With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10-100 μg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 μg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.


Financing public healthcare institutions in Ghana.
The financing of healthcare services has been of a major concern to all governments in the face of increasing healthcare costs. For developing countries, where good health is considered a poverty reduction strategy, it is imperative that the hospitals used in the delivery of healthcare services are well financed to accomplish their tasks. The purpose of this paper is to examine how public hospitals in Ghana are financed, and the challenges facing the financing modes adopted. To achieve the objectives of the study, one major public healthcare institution in Ghana became the main focus. The findings of the study revealed that the main sources of financing the public healthcare institution are government subvention, internally-generated funds and donor-pooled funds. Of these sources, the internally generated fund was regarded as the most reliable, and the least reliable was the donor-pooled funds. Several challenges associated with the various financing sources were identified. These include delay in receipt of government subvention, delay in the reimbursement of services provided to subscribers of health insurance schemes, influence of government in setting user fees, and the specifications to which donor funds are put. The findings of this study have important implications for improving the financing of public healthcare institutions in Ghana. A number of recommendations are provided in this regard.


Acidification Enhances Hybrid N2O Production Associated with Aquatic Ammonia-Oxidizing Microorganisms.
Ammonia-oxidizing microorganisms are an important source of the greenhouse gas nitrous oxide (N2O) in aquatic environments. Identifying the impact of pH on N2O production by ammonia oxidizers is key to understanding how aquatic greenhouse gas fluxes will respond to naturally occurring pH changes, as well as acidification driven by anthropogenic CO2. We assessed N2O production rates and formation mechanisms by communities of ammonia-oxidizing bacteria (AOB) and archaea (AOA) in a lake and a marine environment, using incubation-based nitrogen (N) stable isotope tracer methods with 15N-labeled ammonium (15[Formula: see text]) and nitrite (15[Formula: see text]), and also measurements of the natural abundance N and O isotopic composition of dissolved N2O. N2O production during incubations of water from the shallow hypolimnion of Lake Lugano (Switzerland) was significantly higher when the pH was reduced from 7.54 (untreated pH) to 7.20 (reduced pH), while ammonia oxidation rates were similar between treatments. In all incubations, added [Formula: see text] was the source of most of the N incorporated into N2O, suggesting that the main N2O production pathway involved hydroxylamine (NH2OH) and/or [Formula: see text] produced by ammonia oxidation during the incubation period. A small but significant amount of N derived from exogenous/added 15[Formula: see text] was also incorporated into N2O, but only during the reduced-pH incubations. Mass spectra of this N2O revealed that [Formula: see text] and 15[Formula: see text] each contributed N equally to N2O by a "hybrid-N2O" mechanism consistent with a reaction between NH2OH and [Formula: see text], or compounds derived from these two molecules. Nitrifier denitrification was not an important source of N2O. Isotopomeric N2O analyses in Lake Lugano were consistent with incubation results, as 15N enrichment of the internal N vs. external N atoms produced site preferences (25.0-34.4‰) consistent with NH2OH-dependent hybrid-N2O production. Hybrid-N2O formation was also observed during incubations of seawater from coastal Namibia with 15[Formula: see text] and [Formula: see text]. However, the site preference of dissolved N2O here was low (4.9‰), indicating that another mechanism, not captured during the incubations, was important. Multiplex sequencing of 16S rRNA revealed distinct ammonia oxidizer communities: AOB dominated numerically in Lake Lugano, and AOA dominated in the seawater. Potential for hybrid N2O formation exists among both communities, and at least in AOB-dominated environments, acidification may accelerate this mechanism.


A Technology-Based Pregnancy Health and Wellness Intervention (Two Happy Hearts): Case Study.
The physical and emotional well-being of women is critical for healthy pregnancy and birth outcomes. The Two Happy Hearts intervention is a personalized mind-body program coached by community health workers that includes monitoring and reflecting on personal health, as well as practicing stress management strategies such as mindful breathing and movement. The aims of this study are to (1) test the daily use of a wearable device to objectively measure physical and emotional well-being along with subjective assessments during pregnancy, and (2) explore the user's engagement with the Two Happy Hearts intervention prototype, as well as understand their experiences with various intervention components. A case study with a mixed design was used. We recruited a 29-year-old woman at 33 weeks of gestation with a singleton pregnancy. She had no medical complications or physical restrictions, and she was enrolled in the Medi-Cal public health insurance plan. The participant engaged in the Two Happy Hearts intervention prototype from her third trimester until delivery. The Oura smart ring was used to continuously monitor objective physical and emotional states, such as resting heart rate, resting heart rate variability, sleep, and physical activity. In addition, the participant self-reported her physical and emotional health using the Two Happy Hearts mobile app-based 24-hour recall surveys (sleep quality and level of physical activity) and ecological momentary assessment (positive and negative emotions), as well as the Perceived Stress Scale, Center for Epidemiologic Studies Depression Scale, and State-Trait Anxiety Inventory. Engagement with the Two Happy Hearts intervention was recorded via both the smart ring and phone app, and user experiences were collected via Research Electronic Data Capture satisfaction surveys. Objective data from the Oura ring and subjective data on physical and emotional health were described. Regression plots and Pearson correlations between the objective and subjective data were presented, and content analysis was performed for the qualitative data. Decreased resting heart rate was significantly correlated with increased heart rate variability (r=-0.92, P<.001). We found significant associations between self-reported responses and Oura ring measures: (1) positive emotions and heart rate variability (r=0.54, P<.001), (2) sleep quality and sleep score (r=0.52, P<.001), and (3) physical activity and step count (r=0.77, P<.001). In addition, deep sleep appeared to increase as light and rapid eye movement sleep decreased. The psychological measures of stress, depression, and anxiety appeared to decrease from baseline to post intervention. Furthermore, the participant had a high completion rate of the components of the Two Happy Hearts intervention prototype and shared several positive experiences, such as an increased self-efficacy and a normal delivery. The Two Happy Hearts intervention prototype shows promise for potential use by underserved pregnant women.


Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity.
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.


D-glufosinate as a male sterility agent for hybrid seed production.
A chemical male sterility system based on anther-localized conversion of the inactive D-enantiomer of the herbicide, glufosinate (2-amino-4-(methylphosphinyl)-butanoate) to the phytotoxic L is described. Highly pure D-glufosinate was isolated in >98% enantiomeric excess from the racemate via fermentation with a strain of Escherichia coli expressing the PAT (L-glufosinate N-acetyl transferase) gene and purification of the unreacted D-enantiomer from the broth by ion exchange. A modified (F58K, M213S) form of the D-amino acid oxidase (DAAO) (EC 126.96.36.199) from Rhodosporidium toruloides was designed, tested in vitro and found to efficiently oxidize D-glufosinate to its 2-oxo derivative [2-oxo-4-(methylphosphinyl)-butanoic acid]. Tobacco (Nicotiana tabacum) plants were transformed to express this modified oxidase under control of the TAP1 tapetum-specific promoter. A number of the resultant transgenic lines exhibited complete male sterility that persisted for two or more weeks immediately following foliar treatment with 75 or 200 g/ha of D-glufosinate without exhibiting obvious phytotoxic symptoms or any measurable decline in female fertility. Similarly, plants containing the same construct and, additionally, a PAT gene expressed from a plastocyanin promoter exhibited significantly reduced male fertility and no reduction in female fertility following foliar application of racemic glufosinate. Thus, foliar application of d-glufosinate either purified or as the commercial herbicide, combined with anther expression of a modified DAAO promises to provide a cost-effective conditional chemical male sterility system with the characteristics necessary for practical F₁ hybrid seed production.


Multi-wavelength mid-infrared micro-spectral imaging using semiconductor lasers.
Infrared (IR, 3-12-microm) microscopic spectral imaging is an important analytical technique. Many current instruments employ thermal IR light sources, which suffer the problem of low brightness and high noise. This paper evaluates the system engineering merit in using semiconductor lasers, which offer orders-of-magnitude-higher power, brightness, and lower noise. A microscopic spectral imaging system using semiconductor lasers (quantum cascade) as illuminators, and focal plane array detectors demonstrated a high signal-to-noise ratio (> 20 dB) at video frame rate for a large illuminated area. The comparative advantages of laser vs. thermal light source are analyzed and demonstrated. Microscopic spectral imaging with fixed-wavelength and tunable lasers of 4.6-, 5.1-, 6-, and 9.3-microm wavelength was applied to a number of representative samples that consist of biological tissues (plant and animal), solid material (a stack of laminated polymers), and liquid chemical (benzene). Transmission spectral images with approximately 30-dB dynamic range were obtained with clear evidence of spectral features for different samples. The potential of more advanced systems with a wide coverage of spectral bands is discussed.


Active beam position stabilization of pulsed lasers for long-distance ion profile diagnostics at the Spallation Neutron Source (SNS).
A high peak-power Q-switched laser has been used to monitor the ion beam profiles in the superconducting linac at the Spallation Neutron Source (SNS). The laser beam suffers from position drift due to movement, vibration, or thermal effects on the optical components in the 250-meter long laser beam transport line. We have designed, bench-tested, and implemented a beam position stabilization system by using an Ethernet CMOS camera, computer image processing and analysis, and a piezo-driven mirror platform. The system can respond at frequencies up to 30 Hz with a high position detection accuracy. With the beam stabilization system, we have achieved a laser beam pointing stability within a range of 2 μrad (horizontal) to 4 μrad (vertical), corresponding to beam drifts of only 0.5 mm × 1 mm at the furthest measurement station located 250 meters away from the light source.


Procedural sedation with propofol for emergency DC cardioversion.
Many emergency patients present with cardiac arrhythmias requiring emergency direct current countershock cardioversion (DCCV) as a part of their management. Almost all require sedation to facilitate the procedure. Propofol has been used for procedural sedation in Emergency Medicine since 1995. In 1996, in a review article in Anaesthesia, it was recommended as the drug which most closely approaches the ideal agent for DCCV. However, the existing evidence for the dosage requirements and safety of propofol in emergency DCCV is limited. We report a prospective case series of patients who underwent sedation-facilitated DCCV using propofol in the emergency department with both sedation and DCCV delivered by emergency physicians. The results indicate propofol is a safe drug for procedural sedation to facilitate emergency DCCV in patients with an atrial tachyarrhythmia without any evidence of haemodynamic compromise. A dose of 1 mg/kg appears to be safe in the majority of these patients. Using the adverse event reporting tool produced by the World SIVA International Sedation Task Force there were no moderate or sentinel adverse events in these patients. A reduced dose should be considered in older patients to prevent transient complications. Propofol at a dose of 0.5 mg/kg appears to be a safe drug for procedural sedation to facilitate emergent or urgent DCCV in patients with an atrial tachyarrhythmia with evidence of haemodynamic compromise. There were no sentinel adverse events associated with its use. Evidence to support the use of propofol to facilitate emergency DCCV for ventricular tachycardia is limited.


Purification and characterization of a beta-glucosidase from solid-state cultures of Humicola grisea var. thermoidea.
The thermophilic fungus Humicola grisea var. thermoidea produced beta-glucosidase activity when grown in a solid-state culture on wheat bran as carbon source. A beta-glucosidase was purified to apparent homogeneity by ultrafiltration, gel filtration chromatography on Sephacryl S-100, and ion-exchange chromatography on S-Sepharose, as judged by sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE) on a 12.5% (w/v) slab gel. The enzyme had a molecular mass of 82 and 156 kDa, as estimated by SDS-PAGE and gel filtration on a high performance liquid chromatographic column, respectively, suggesting that the native enzyme may consist of two identical subunits. The purified enzyme was thermostable at 60 degrees C for 1 h with a half-life of 15 min at 65 degrees C, and displayed optimum activity at 60 degrees C and a pH range. of 4.0-4.5. The Km and Vmax values for p-nitrophenyl beta-D-glucopyranoside were determined to be 0.316 mM and 0.459 IU.mL-1, respectively. D-Glucose, D-gluconic acid lactone, Hg2+, Cu2+, and Mn2+ inhibited beta-glucosidase activity. The enzyme activity was competitively inhibited by D-glucose (ki = 0.6 mM). The purified enzyme was very active against cellobiose and p-nitrophenyl beta-D-glucopyranoside.


[Acute kidney failure caused by hantavirus infection].
A 37-year-old man suddenly fell ill with high fever (up to 39.6 degrees C), headache and lumbar pain. There was marked thrombocytopenia (minimal level of 48,000/microliters), moderate anaemia and a slow rise in serum lipase concentration to maximally 1352 U/l. Marked sinus bradycardia (to as low as 34 beats/min) occurred in the further course of the disease, as well as upper abdominal pain (endoscopically diagnosed as antral gastritis), subileus and splenomegaly. Two haemodialysis treatments were needed because of acute renal failure. An IgG antibody titre of 1:512 and an IgM titre of 1:80 against hantavirus antigen confirmed that this virus was responsible for the haemorrhagic fever with renal syndrome. This infection, transmitted by wild rodents and frequently observed in Asian countries, has a rising incidence in Central Europe. It should be included in the differential diagnosis of acute renal failure of uncertain cause.


An identification of invariants in life history traits of amphibians and reptiles.
While many morphological, physiological, and ecological characteristics of organisms scale with body size, some do not change under size transformation. They are called invariant. A recent study recommended five criteria for identifying invariant traits. These are based on that a trait exhibits a unimodal central tendency and varies over a limited range with body mass (type I), or that it does not vary systematically with body mass (type II). We methodologically improved these criteria and then applied them to life history traits of amphibians, Anura, Caudata (eleven traits), and reptiles (eight traits). The numbers of invariant traits identified by criteria differed across amphibian orders and between amphibians and reptiles. Reproductive output (maximum number of reproductive events per year), incubation time, length of larval period, and metamorphosis size were type I and II invariant across amphibians. In both amphibian orders, reproductive output and metamorphosis size were type I and II invariant. In Anura, incubation time and length of larval period and in Caudata, incubation time were further type II invariant. In reptiles, however, only number of clutches per year was invariant (type II). All these differences could reflect that in reptiles body size and in amphibians, Anura, and Caudata metamorphosis (neotenic species go not through it) and the trend toward independence of egg and larval development from water additionally constrained life history evolution. We further demonstrate that all invariance criteria worked for amphibian and reptilian life history traits, although we corroborated some known and identified new limitations to their application.


A case of metastatic haemangiopericytoma to the thyroid gland: Case report and literature review.
Haemangiopericytoma (HPC) is a mesenchymal neoplasm accounting for a minority of all vascular tumours. HPC mostly arises in the lower extremities and the retroperitoneum, while the head and neck area is the third most common site. The majority of HPCs are histologically benign. However, a small percentage possess atypical features, such as a high mitotic rate, high cellularity and foci of necrosis. We report a case of classical abdominal HPC that presented 7 years after the first surgical resection with thyroid metastases of malignant HPC. Microscopic examination revealed multiple hypercellular nodules with an infiltrative growth pattern. These nodules consisted of tightly packed fusiform or spindle-shaped cells with nuclear polymorphism and an increased mitotic rate. The tumour cells exhibited a marked expression of CD34. Cells were arranged around a prominent vascular network, occasionally with a 'staghorn' configuration. The results of this study support and confirm the theory that HPC is a rare neoplasm with unpredictable behaviour, as largely debated in the international literature. Therefore, this study emphasized the importance of applying strict diagnostic criteria in making the most appropriate diagnosis.


Thalidomide induce response in patients with corticosteroid-resistant or relapsed ITP by upregulating Neuropilin-1 expression.
Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism. 50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected. Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders. Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.


New developments in allotransplant immunology.
After allogeneic stem cell transplantation, the establishment of the donor's immune system in an antigenically distinct recipient confers a therapeutic graft-versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and protracted immune dysfunction. In the last decade, a molecular-level description of alloimmune interactions and the process of immune recovery leading to tolerance has emerged. Here, new developments in understanding alloresponses, genetic factors that modify them, and strategies to control immune reconstitution are described. In Section I, Dr. John Barrett and colleagues describe the cellular and molecular basis of the alloresponse and the mechanisms underlying the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL) effect. Increasing knowledge of leukemia-restricted antigens suggests ways to separate GVHD and GVL. Recent findings highlight a central role of hematopoietic-derived antigen-presenting cells in the initiation of GVHD and distinct properties of natural killer (NK) cell alloreactivity in engraftment and GVL that are of therapeutic importance. Finally, a detailed map of cellular immune recovery post-transplant is emerging which highlights the importance of post-thymic lymphocytes in determining outcome in the critical first few months following stem cell transplantation. Factors that modify immune reconstitution include immunosuppression, GVHD, the cytokine milieu and poorly-defined homeostatic mechanisms which encourage irregular T cell expansions driven by immunodominant T cell-antigen interactions. In Section II, Prof. Anne Dickinson and colleagues describe genetic polymorphisms outside the human leukocyte antigen (HLA) system that determine the nature of immune reconstitution after allogeneic stem cell transplantation (SCT) and thereby affect transplant outcomethrough GVHD, GVL, and transplant-related mortality. Polymorphisms in cytokine gene promotors and other less characterized genes affect the cytokine milieu of the recipient and the immune reactivity of the donor. Some cytokine gene polymorphisms are significantly associated with transplant outcome. Other non-HLA genes strongly affecting alloresponses code for minor histocompatibility antigens (mHA). Differences between donor and recipient mHA cause GVHD or GVL reactions or graft rejection. Both cytokine gene polymorphisms (CGP) and mHA differences resulting on donor-recipient incompatibilities can be jointly assessed in the skin explant assay as a functional way to select the most suitable donor or the best transplant approach for the recipient. In Section III, Dr. Nelson Chao describes non-pharmaceutical techniques to control immune reconstitution post-transplant. T cells stimulated by host alloantigens can be distinguished from resting T cells by the expression of a variety of activation markers (IL-2 receptor, FAS, CD69, CD71) and by an increased photosensitivity to rhodamine dyes. These differences form the basis for eliminating GVHD-reactive T cells in vitro while conserving GVL and anti-viral immunity. Other attempts to control immune reactions post-transplant include the insertion of suicide genes into the transplanted T cells for effective termination of GVHD reactions, the removal of CD62 ligand expressing cells, and the modulation of T cell reactivity by favoring Th2, Tc2 lymphocyte subset expansion. These technologies could eliminate GVHD while preserving T cell responses to leukemia and reactivating viruses.


Comparative effects of telmisartan and valsartan on insulin resistance in hypertensive patients with metabolic syndrome.
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglycemia, dyslipidemia, hypertension and increased waist circumference. Individuals with this syndrome are at increased risk for development of cardiovascular disease. Since an insulin-resistance state has a critical role in the development of MetS, there is growing concern about insulin-sensitizing effects of antihypertensives, including angiotensin II receptor blockers (ARBs). Telmisartan has been reported to have an effect on the activity of peroxisome proliferator-activated receptor gamma, a well-known target for insulin-sensitizing antidiabetic drugs. The aim of this study was to determine the effects of administration of two different ARBs at low doses (telmisartan at 20 mg/day and valsartan at 40 mg/day) on insulin sensitivity. Patients with MetS meeting the Japanese criteria were treated with telmisartan or valsartan for 4 weeks in combination with lifestyle modification. A significant reduction in blood pressure was found after 4 weeks of both treatments. The homeostasis model assessment of insulin resistance (HOMA-R) was significantly reduced by telmisartan compared to the baseline value (3.11+/-2.06 vs 2.56+/-1.48, p=0.031) but was not significantly changed by valsartan. A statistically significant correlation was found between HOMA-R at baseline and changes in HOMA-R after 4 weeks of treatment only in telmisartan-treated subjects. Body mass index, glycosylated hemoglobin and lipid profile were not changed by either treatment. Our data revealed that treatment with telmisartan even at a low dose improves insulin sensitivity in hypertensive patients with MetS. This ameliorating effect of telmisartan on glucose metabolism clinically deserves to be considered.


Proton bridging in the interactions of thrombin with small inhibitors.
Thrombin is the pivotal serine protease enzyme in the blood cascade system. Phe-Pro-Arg-chloromethylketone (PPACK), phosphate, and phosphonate ester inhibitors form a covalent bond with the active-site Ser of thrombin. PPACK, a mechanism-based inhibitor, and the phosphate/phosphonate esters form adducts that mimic intermediates formed in reactions catalyzed by thrombin. Therefore, the dependence of the inhibition of human alpha-thrombin on the concentration of these inhibitors, pH, and temperature was investigated. The second-order rate constant (ki/Ki) and the inhibition constant (Ki) for inhibition of human alpha-thrombin by PPACK are (1.1 +/- 0.2) x 10(7) M(-1) s(-1) and (2.4 +/- 1.3) x 10(-8) M, respectively, at pH 7.00 in 0.05 M phosphate buffer and 0.15 M NaCl at 25.0 +/- 0.1 degrees C, in good agreement with previous reports. The activation parameters at pH 7.00 in 0.05 M phosphate buffer and 0.15 M NaCl are as follows: DeltaH = 10.6 +/- 0.7 kcal/mol, and DeltaS = 9 +/- 2 cal mol(-1) degrees C(-1). The pH dependence of the second-order rate constants of inhibition is bell-shaped. Values of pKa1 and pKa2 are 7.3 +/- 0.2 and 8.8 +/- 0.3, respectively, at 25.0 +/- 0.1 degrees C. A phosphate and a phosphonate ester inhibitor gave higher values, 7.8 and 8.0 for pKa1 and 9.3 and 8.6 for pKa2, respectively. They inhibit thrombin more than 6 orders of magnitude less efficiently than PPACK does. The deuterium solvent isotope effect for the second-order rate constant at pH 7.0 and 8.3 at 25.0 +/- 0.1 degrees C is unity within experimental error in all three cases, indicating the absence of proton transfer in the rate-determining step for the association of thrombin with the inhibitors, but in a 600 MHz 1H NMR spectrum of the inhibition adduct at pH 6.7 and 30 degrees C, a peak at 18.10 ppm with respect to TSP appears with PPACK, which is absent in the 1H NMR spectrum of a solution of the enzyme between pH 5.3 and 8.5. The peak at low field is an indication of the presence of a short-strong hydrogen bond (SSHB) at the active site in the adduct. The deuterium isotope effect on this hydrogen bridge is 2.2 +/- 0.2 (phi = 0.45). The presence of an SSHB is also established with a signal at 17.34 ppm for a dealkylated phosphate adduct of thrombin.


Longitudinal time-dependent effects of irradiation on multidrug resistance in a non-small lung cancer cell line.
Multidrug resistance (MDR) in cancer is known to decrease the therapeutic efficacy of chemotherapy. The effects of irradiation on MDR in cancer cells remain unclear. Tc-99m methoxyisobutylisonitrile (MIBI) exhibits the same ATP-binding cassette (ABC) transporter kinetics as the chemotherapeutic compound doxorubicin. In this study, we investigated the synergistic effects of chemotherapeutics and irradiation [0 Gy: C (control) group; 3, 6, 9, 12 Gy: I (irradiation) group] in the human non-small lung cancer cell line H1299 exhibiting MDR, on MIBI and doxorubicin ABC transporter kinetics, in vitro and in vivo, respectively. In vitro, inhibition of H1299 cell proliferation by irradiation was found to be irradiation dose dependent. The degree and duration of MDR inhibition in vitro in H1299 were also dose dependent. In the cells of both the C group and 3-Gy I group, no significant difference of MIBI accumulation was observed. In the 6-Gy I group, a higher MIBI accumulation was observed at only 7 days after irradiation relative to the C group. A higher MIBI accumulation in the 9- and 12-Gy I groups with a significant difference from the C group was observed at 4 to 14 days after irradiation. A significant negative correlation between intracellular MIBI accumulation and cell replication was found. In vivo, high accumulation and retention of doxorubicin were observed in irradiated tumors in the H1299 xenograft mice group at 4 to 14 days after 9-Gy irradiation compared with the control mice group. These results provide evidence for a synergistic effect of concurrent chemotherapy and radiotherapy.


Ultrasound Image-Guided Nerve Block Combined with General Anesthesia under an Artificial Intelligence Algorithm on Patients Undergoing Radical Gastrectomy for Gastric Cancer during and after Operation.
This study was aimed at investigating the location of gastric cancer by using a gastroscope image based on an artificial intelligence algorithm for gastric cancer and the effect of ultrasonic-guided nerve block combined with general anesthesia on patients undergoing gastric cancer surgery. A total of 160 patients who were undergoing gastric cancer surgery from March 2019 to March 2021 were collected as the research objects, and the convolutional neural network (CNN) algorithm was used to segment the gastroscope image of gastric cancer. The patients were randomly divided into a simple general anesthesia group of 80 cases and a transversus abdominis plane block combined with rectus abdominis sheath block combined with the general anesthesia group of 80 cases. Then, compare the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) at the four time points T0, T1, T2, and T3. The times of analgesic drug use within 48 hours after operation and postoperative adverse reactions were recorded. The visual analog scale (VAS) scores were also recorded at 4 h, 12 h, 24 h, and 48 h. The results show that the image quality after segmentation is good: the accuracy of tumor location is 75.67%, which is similar to that of professional endoscopists. Compared with the general anesthesia group, the transversus abdominis plane block combined with the rectus sheath block combined with the general anesthesia group had fewer anesthetics, and the difference was statistically significant (P < 0.05). Compared with the general anesthesia group, SBP, DBP, and HR were significantly reduced at T1, T2, and T3 in the transverse abdominis plane block combined with rectus sheath block and general anesthesia group (P < 0.05). Compared with the simple general anesthesia group, the VAS scores of the transversus abdominis plane block combined with rectus sheath block combined with the general anesthesia group decreased at 4 h, 12 h, and 24 h after surgery, and the difference was statistically significant (P < 0.05). The number of analgesics used in transversus abdominis plane block combined with the rectus sheath block combined with the general anesthesia group within 48 hours after operation was significantly less than that in the general anesthesia group, and the difference was statistically significant (P < 0.05). The average incidence of adverse reactions in the nerve block combined with the general anesthesia group was 2.5%, which was lower than the average incidence of 3.75% in the general anesthesia group. In summary, the CNN algorithm can accurately segment the lesions in the ultrasonic images of gastric cancer, which was convenient for doctors to make a more accurate judgment on the lesions, and provided a basis for the preoperative examination of radical gastrectomy for gastric cancer. Ultrasonic-guided nerve block combined with general anesthesia can effectively improve the analgesic effect of radical gastrectomy for gastric cancer, reduced intraoperative and postoperative adverse reactions and analgesic drug dosage, and had a good effect on postoperative recovery of patients. The combined application of these two methods can further improve the precision treatment of gastric cancer patients and accelerate postoperative recovery.


Amalgam fillings and cognitive abilities in a representative sample of the elderly population.
The ongoing controversial discussion about a possible negative effect of amalgam fillings on the cognitive abilities and the pathogenesis dementia was the objective of the present study. A total of 300 patients aged from 70 to 103 years were selected from the multidisciplinary 'Berlin Aging Study' (BASE). The sample was heterogeneous concerning lifestyle, education and social prestige. According to their dental state subjects were allocated into three groups: edentate > or = 20 years (I) and residual teeth without (II) or with (III) amalgam restorations. All groups were matched for age and gender. Dental examinations and various psychiatric as well as psychological assessments were carried out by professionals within the protocol of the BASE. Tests were chosen to reveal the presence and degree of dementia and assess cognitive abilities such as 'perceptual speed', 'reasoning', 'memory', 'fluency' and 'knowledge'. The present findings negate a correlation between the dental state and the pathogenesis of dementia and the physiological age-related decline in cognitive abilities. Thus the presence of amalgam fillings did neither correlate to a demented mental condition nor an impaired cognitive performance.


Rating the hazard from intense sounds: putting theory into practice.
Basilar membrane mechanics appear to be largely responsible for noise induced temporary threshold shift (TTS). Upon noise exposure, the single fiber loses sensitivity and sharpness. The amplitude and configuration (sharpness) of the basilar membrane vibration pattern is reduced. The "best frequency" changes about half an octave. The result is threshold shift and reduced frequency discrimination. The maximal TTS is generally seen one octave above the peak frequency of the stimulus. There appears to be a critical intensity level for noise exposure. Below the critical level little or no hearing damage will develop regardless of exposure time. Beyond the critical level, extensive damage will be caused even after short exposure time. The critical level appears to be a rather absolute measure: in animals, the state of the inner hair cells may change from "no loss" to "extensive loss" upon a stimulus increase of only 3dB. Addition of acoustical energy at a frequency different from that of the original stimulus, may reduce the threshold shift induced by the original stimulus alone. Sound in one ear may also influence the susceptibility of the other. Compared with its isoenergetic impulse noise, a continuous noise generally must be given a 3dB increase (its energy must be doubled) if both stimuli shall produce similar threshold shifts. Factors like frequency distribution, level, duration number, repetition rate and time distribution/presentation pattern of exposure apparently have to be considered in future damage risk criteria. Meanwhile isoenergy, or possibly "A-weighted" isoenergy, is our best indicator for noise hazard.


Long form of cellular FLICE-inhibitory protein interacts with Daxx and prevents Fas-induced JNK activation.
Since Fas-induced apoptosis is major pathway to eliminate unwanted or uncontrolled cells, many types of human cancer cells develop tactful mechanisms to get resistance against the apoptosis. One of the resistant mechanisms in human cancer is overexpression of FLICE-inhibitory protein (c-FLIP), human homolog of viral protein v-FLIP. c-FLIP has multiple splice variants at transcriptional level or two isoforms at protein level, a long (c-FLIP(L)) and a short form of c-FLIP (c-FLIP(S)). However, functional differences between these variants are not fully understood. In this study, we show that c-FLIP(L) but not c-FLIP(S) physically binds to Daxx through interaction between C-terminal domain of c-FLIP(L) and Fas-binding domain of Daxx, an alternative Fas signaling adaptor. Fas-induced cell death and JNK activation are sensitive to Fas stimulation in cell lines carrying undetectable level of c-FLIP(L). To support this, overexpression of c-FLIP(L) but not of c-FLIP(S) renders the cells resistant to Fas-induced cell death and to JNK activation. In signaling context, the interaction of c-FLIP(L) with Daxx is likely to inhibit JNK activation by preventing the normal interaction of Daxx and Fas, which is known to lead to apoptosis via JNK activation. This study implies that through this new mechanism, c-FLIP(L), acting at both FADD- and Daxx-mediated signaling pathways, may be involved in complete inhibition of Fas-induced cell death and may provide an answer to why c-FLIP(L) is more abundant and effective than c-FLIP(S).


Occurrence of black Aspergilli in indoor environments of six countries.
Black Aspergilli (Aspergillus section Nigri) are widely distributed in various habitats. They act as food spoilage organisms, human pathogens, and mycotoxin producers and are frequently encountered in indoor environments. Black Aspergilli, specifically A. niger, A. welwitschiae, and A. carbonarius, produce different ochratoxins and fumonisins. Ochratoxins are known to induce renal disorders following inhalation, which necessitates the determination of potential mycotoxin-producing species in our environment. This paper aimed to compare the diversity and species distribution of black Aspergilli in the indoor environments of six different countries using morphological and molecular methods. A total of 178 black Aspergillus isolates were identified from six countries. In contrast with results from previous studies, A. niger was not the only black Aspergillus detected in indoor air. Species distribution differed among countries, although the distribution in European countries (Croatia, Hungary, the Netherlands, and Turkey) with a temperate climate was considerably similar. The highest species diversity was observed in indoor samples from Thailand, while the lowest was found in Algeria. Potentially ochratoxin- and fumonisin-producing fungi were detected in the indoor air of all six countries. Further studies need to clarify the effect of these fungi and their mycotoxins on human and animal health.


Gas chromatography-electron ionization and chemical ionization mass spectrometric analysis of urinary phenmetrazine after derivatization with 4-carbethoxyhexafluorobutyryl chloride--a new derivative.
Phenmetrazine is a central nervous system stimulant currently used as an anorectic agent. The drug is abused and is reported to cause death from overdose. We describe a new derivatization method for phenmetrazine using 4-carbethoxyhexafluorobutyryl chloride. Quantitation of urinary phenmetrazine can be easily achieved by using N-ethyl amphetamine as an internal standard. The electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of phenmetrazine showed a molecular ion at m/z 427 and a base peak at m/z 70. In the methane chemical ionization mass spectrum, the base peak was observed at m/z 428 (protonated molecular ion). In the electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of the internal standard, N-ethyl amphetamine we did not observe a molecular ion. However, in the chemical ionization mass spectrum, the protonated molecular ion at m/z 414 was the base peak. The retention time of derivatized phenmetrazine (8.4 min) was substantially longer than the retention time of the underivatized molecule. Moreover, underivatized phenmetrazine showed poor peak shape (substantial tailing) while derivatized phenmetrazine had excellent chromatographic properties. The within-run and between-run precisions of the assay were 2.6% and 3.1% respectively at a urinary phenmetrazine concentration of 10 micrograms/mL. The assay was linear for urinary phenmetrazine concentration of 1 to 100 micrograms/mL with a detection limit of 0.2 microgram/mL.