High-pressure washing treatments to remove obscure mealybug (Homoptera: Pseudococcidae) and lightbrown apple moth (Lepidoptera: Tortricidae) from harvested apples.
Mixed life stages of obscure mealybug, Pseudococcus viburni (Signoret), and late 1st-instar or early 2nd-instar lightbrown apple moth, Epiphyas postvittana (Walker), on 'Royal Gala' apples (Malus domestica Borkhausen) were exposed to standard packhouse processing with and without addition of high-pressure apple washer treatments. Insect removal and mortality were assessed. After standard packhouse processing approximately 60% of P. viburni remained on their host apples. The 2 high-pressure apple washer treatments (500 and 800 psi at 2.0 rods/s) were equally effective and significantly reduced the number of P. viburni on apples compared with the packhouse control. High-pressure apple washer removal by location decreased in the following order: calyx cavity outside the sepals > cheek approximately stem cavity > or = calyx beneath sepals. About half of the E. postvittana larvae infesting apples was removed by standard packhouse processing. Removal rates were similar for all locations on open-calyxed apples. However, no removal occurred from the calyx beneath the sepals if the apple calyx was closed. All 4 high-pressure apple washer treatments tested (500 and 800 psi at 1.0 and 2.0 rods/s) halved the number of larvae on the apple exterior relative to the packhouse control. The pattern of removal for larvae on open-calyxed apples was calyx outside sepals approximately stem cavity > calyx beneath the sepals approximately cheek. A similar pattern was evident for larvae on closed-calyxed apples, except insects beneath the sepals evaded removal. The persistence of insects on the apple cheek reflects the high proportion of larvae inside tunnels in this location compared with other apple locations. Removal of internally positioned insects was much lower than that of externally positioned insects.


RNA circles with minimized immunogenicity as potent PKR inhibitors.
Exon back-splicing-generated circular RNAs, as a group, can suppress double-stranded RNA (dsRNA)-activated protein kinase R (PKR) in cells. We have sought to synthesize immunogenicity-free, short dsRNA-containing RNA circles as PKR inhibitors. Here, we report that RNA circles synthesized by permuted self-splicing thymidylate synthase (td) introns from T4 bacteriophage or by Anabaena pre-tRNA group I intron could induce an immune response. Autocatalytic splicing introduces ∼74 nt td or ∼186 nt Anabaena extraneous fragments that can distort the folding status of original circular RNAs or form structures themselves to provoke innate immune responses. In contrast, synthesized RNA circles produced by T4 RNA ligase without extraneous fragments exhibit minimized immunogenicity. Importantly, directly ligated circular RNAs that form short dsRNA regions efficiently suppress PKR activation 103- to 106-fold higher than reported chemical compounds C16 and 2-AP, highlighting the future use of circular RNAs as potent inhibitors for diseases related to PKR overreaction.


Contrast modulated maskers: test of a late nonlinearity hypothesis.
The contrast threshold for detecting a low frequency test grating in the presence of a contrast-modulated high frequency masker is heavily dependent upon the phase relations between the gratings: test stimuli in + or - cosine phase are much more detectable than those in + or -sine phase. The present study tests a new hypothesis of these and related phenomena. It is based on the report by Derrington (1987) that recordings from cat geniculate on-center and off-center X-cells exhibit significant point nonlinearities. The major empirical finding of this study is that for highly practiced observers, sine-phase test stimuli and cosine-phase test stimuli are similar in two important respects: (1) there exist phase uncertainty effects; that is, detection thresholds for test stimuli differing in phase by 180 degrees are elevated when they are intermixed within the same block of trials, rather than being presented in separate blocks; (2) phase identification thresholds for test stimuli differing in phase by 180 degrees are the same as their detection thresholds. The new nonlinearity hypothesis cannot account for the results obtained with sine-phase test stimuli, though it gives a better account of the results with cosine-phase stimuli than does the early nonlinearity hypothesis which was tested and rejected by Nachmias and Rogowitz (1983).


Room for improvement: Palliating the ego in feedback-resistant medical students.
Feedback in medical education provides the impetus for growth in a field pressured to demonstrate continuous progress. Unfortunately, as it always incorporates some level of judgment, certain students appear more resistant than receptive to receiving feedback. Coupled with the ubiquitous stressors of medicine-examinations, perpetual knowledge acquisition, competition for employment-there subtly emerges a learning environment in which the mindset of medical trainees morphs from collegiality to outperformance of one's peers. As the unconscious mind is ultimately focused on self-protection, the cognitive response of reflecting upon received feedback is overcome by an emotional response to safeguard one's self-image against criticism in a culture of comparison. Although self-confidence plays a critical role in mitigating burnout, the relationship between resiliency and ego-armoring is rarely discussed in the literature. Consequently, despite the best intentions of educators in fostering clinical maturity among their trainees, the fact remains that insecurity, inadequacy and invulnerability continue to drive feedback-resistance among medical students.


A competing risk nomogram to predict cancer-specific mortality of patients with late-onset colorectal cancer.
This study aimed to compare the clinical characteristics and survival differences between early-onset colorectal cancer (EOCRC) patients and late-onset colorectal cancer (LOCRC) patients, identify the risk factors for cancer-specific mortality (CSM) in LOCRC patients and construct a mortality risk assessment nomogram. CRC patients diagnosed pathologically between 2010 and 2019 in the SEER database were included and divided into the early-onset group and the late-onset group, and the late-onset group was divided into the training and validation sets. The Fine-Gray competing risk model was applied to analyze the prognostic factors of LOCRC patients and establish a competing risk nomogram for CSM. There are differences in the distribution of multiple clinical features between the early-onset group and the late-onset group. Age, tumor size, histological type, pathological grading, T stage, N stage, M stage, SEER stage, primary tumor surgery, metastatic lesion surgery, radiotherapy, chemotherapy, neural invasion, and carcinoembryonic antigen (CEA) were independent influencing factors of the CSM rate in LOCRC patients. The C-index of the prognosis model outweighed 0.8, and the calibration curves fitted the reference line well. The CSM competing risk nomogram for LOCRC patients in this study had acceptable predictive performance that could be applied to the clinic.


Self-mutilation and sleep stage in the Lesch-Nyhan syndrome.
Correlation of self-mutilation and sleep stage in the Lesch-Nyhan syndrome was studied by a polygraphic method. Five patients and three control boys were monitored with EEG, EOG, EMG, ECG and respiration throughout the night. The results were as follows: 1. The sleep-time of the patients was much disturbed during the night. 2. Decreased REM density was noticed with low DQ of the patients. 3. Self-mutilation during sleep-time was observed a lot in stages 1, 2, and REM in two cases. 4. No correlation was observed between body movement and self-mutilation in the Lesch-Nyhan syndrome. These data suggested functional disorders of the frontal lobe in the patients.


Is immunotherapy for habitual aborters an immunologically hazardous procedure for infants?
Physical development and tests of immunologic function are reported from the first year of life for 13 infants born to mothers who were habitual aborters and who had undergone subcutaneous vaccination with their husband's lymphocytes. The mean weight of the infants at birth was 2,975 +/- 540 g, including one infant who was small for dates. Physical development parameters for the first year were all within normal range. Immunologic studies were performed at ages 0, 1, 3, 6, 9, and 12 months. The studies included the following: (1) serum levels of immunoglobulins and complement components; (2) the number of peripheral blood lymphocytes (PBL) and their subpopulations; and (3) proliferative responses by PBL against unrelated lymphocytes and some mitogens (pokeweed, phytohemagglutinin, and concanavalin A). All were normal when compared with studies of infants of nonimmunized mothers. These observations suggested that subcutaneous vaccination of women with their husband's lymphocytes did not result in any adverse effects on their infants' physical or immunologic development.


Is there still a role for double-contrast barium enema examination?
The role of double-contrast barium enema examination (DCBE) in screening for colorectal carcinoma has evolved considerably in recent years. This review will discuss the current indications for DCBE and contrast fluoroscopy of the colon and the anticipated future role of these studies.


Risk factors for development of nephropathy in patients with a diabetic Charcot foot.
Charcot foot is a rare complication to neuropathy and can cause severe foot deformities and ulcerations, which often require prolonged antibiotical treatment. The objective of this retrospective study was to investigate whether this treatment is associated to impaired renal function. In total, 163 patients were included, of whom 105 (64%) had received β-lactam antibiotics for a mean total duration of 13.0 months. There was a significant increase in the urine albumin/creatinine ratio in the group that received antibiotics (p = 0.017), and the use of antibiotics was associated to a subsequent diagnosis of nephropathy (p = 0.01). Patients treated with antibiotics had a 21.9% risk of developing subsequent nephropathy versus 5.2% for patients not treated with antibiotics. We suggest increased awareness on signs of nephropathy in patients with severe Charcot foot.


Atmospheric chemistry of hydrofluoroethers: Reaction of a series of hydrofluoroethers with OH radicals and Cl atoms, atmospheric lifetimes, and global warming potentials.
The kinetics of the OH radical and Cl atom reactions with nine fluorinated ethers have been studied by the relative rate method at 298 K and 1013 hPa using gas chromatography-mass spectroscopy (GC-MS) detection: k(OH + CH3CH2OCF3) = (1.55 +/- 0.25) x 10(-13), k(OH + CF3CH2OCH3) = (5.7 +/- 0.8) x 10(-13),k(OH + CF3CH2OCHF2) = (9.1 +/- 1.1) x 10(-15), k(OH + CF3CHFOCHF2) = (6.5 +/- 0.8) x 10(-15), k(OH + CHF2CHFOCF3) = (6.8 +/- 1.1) x 10(-15), k(OH + CF3CHFOCF3) < 1 x 10(-15), k(OH + CF3CHFCF2OCHF2) = (1.69 +/- 0.26) x 10(-14), k(OH + CF3CHFCF2OCH2CH3) = (1.47 +/- 0.13) x 10(-13), k(OH + CF3CF2CF2OCHFCF3) < 1 x 10(-15), k(Cl + CH3CH2OCF3) = (2.2 +/- 0.8) x 10(-12), k(Cl + CF3CH2OCH3) = (1.8 +/- 0.9) x 10(-11), k(Cl + CF3CH2OCHF2) = (1.5 +/- 0.4) x 10(-14), k(Cl + CF3CHFOCHF2) = (1.1 +/- 1.9) x 10(-15), k(Cl + CHF2CHFOCF3) = (1.2 +/- 2.0) x 10(-15), k(Cl + CF3CHFOCF3) < 3 x 10(-15), k(Cl + CF3CHFCF2OCHF2) < 6 x 10(-16), k(Cl + CF3CHFCF2OCH2CH3) = (3.1 +/- 1.1) x 10(-12), and k(Cl + CF3CF2CF2OCHFCF3) < 3 x 10(-15) cm3 molecule(-1) s(-1). The error limits include three standard deviations (3 sigma) from the statistical data analyses, as well as the errors in the rate coefficients of the reference compounds that are used. Infrared absorption cross sections and estimates of the trophospheric lifetimes and the global warming potentials of the fluorinated ethers are presented. The atmospheric degradation of the compounds is discussed.


Comparative molecular cytogenetic analysis of three Leuciscus species (Pisces, Cyprinidae) using chromosome banding and FISH with rDNA.
A comparative molecular cytogenetic analysis was performed on three species of the genus Leuciscus viz. ide L. idus, chub L. cephalus and dace L. leuciscus distributed in Poland, using C-, Ag- and chromomycin A(3) (CMA(3))-stainings and fluorescence in situ hybridization (FISH) with 5.8S + 28S rDNA as a probe. Although the three species examined shared 2n = 50 chromosomes and the largest acrocentric chromosome pair in the complement, they were characterized with karyotypic differences in terms of the number of uni- and biarmed chromosomes and the localization of nucleolar organizer regions (NORs) revealed by Ag-staining and FISH. L. idus and L. cephalus showed the rDNA sites on the long arms of one submetacentric (SM) chromosome pair and on the short arms of one subtelocentric (ST) chromosome pair, respectively. These NORs were CMA(3)-positive, GC-rich and C-positive heterochromatic sites in both species. Such chromosome banding features were also true for four NORs localizing on one of each SM and ST pair in L. leuciscus, but considerable numerical NOR polymorphism became apparent with Ag-staining and FISH due to a different combination of these NOR-bearing SMs and STs in this dace. The present results indicate that the molecular cytogenetic analysis applied herein may become useful to elucidate the karyotype evolution and phylogenetic relationships among the species in the genus Leuciscus and other related groups.


Formation of iron oxide nanoparticles for the photooxidation of water: Alteration of finite size effects from ferrihydrite to hematite.
Iron oxide nanoparticles represent a promising low-cost environmentally-friendly material for multiple applications. Especially hematite (α-Fe2O3) nanoparticles demonstrate great possibilities in energy storage and photoelectrochemistry. A hydrothermal one-pot synthesis can be used to synthesise hematite nanoparticles. Here, the particle formation, nucleation and growth of iron oxide nanoparticles using a FeCl3 precursor over time is monitored. The formation of 6-line ferrihydrite seeds of 2-8 nm which grow with reaction time and form clusters followed by a phase transition to ~15 nm hematite particles can be observed with ex situ X-ray diffraction (XRD), transmission electron microscopy (TEM), Raman and UV/Vis spectroscopy. These particles grow with reaction time leading to 40 nm particles after 6 hours. The changes in plasmon and electron transition patterns, observed upon particle transition and growth lead to the possibility of tuning the photoelectrochemical properties. Catalytic activity of the hematite nanoparticles can be proven with visible light irradiation and the use of silver nitrate as scavenger material. The generation of elementary silver is dependent on the particle size of iron oxide nanoparticles while only slight changes can be observed in the oxygen generation. Low-cost nanoscale hematite, offers a range of future applications for artificial photosynthesis.


Simultaneity constancy: detecting events with touch and vision.
What are the consequences of visual and tactile neural processing time differences when combining multisensory information about an event on the body's surface? Visual information about such events reaches the brain at a time that is independent of the location of the event. However, tactile information about such events takes different amounts of time to be processed depending on the distance between the stimulated surface and the brain. To investigate the consequences of these differences, we measured reaction times to touches and lights on different parts of the body and the perceived subjective simultaneity (PSS) for various combinations. The PSSs for pairs of stimuli were predicted by the differences in reaction times. When lights and touches were on different body parts (i.e. the hand and foot) a trend towards compensation for any processing time differences was found, such that simultaneity was veridically perceived. When stimuli were both on the foot, subjects perceived simultaneity when the light came on significantly earlier than the touch, despite similar processing times for these stimuli. When the stimuli were both on the hand, however, there was complete compensation for the significant processing time differences between the light and touch such that simultaneity was correctly perceived, a form of simultaneity constancy. To identify if there was a single simultaneity constancy mechanism or multiple parallel mechanisms, we altered the PSS of an auditory-visual stimulus pair and looked for effects on the PSS of a visual-touch pair. After repeated exposure to a light/sound pair with a fixed time lag between them, there was no effect on the PSS of a touch-light pair, suggesting multiple parallel simultaneity constancy mechanisms.


Critical differences between two classical surgical approaches for middle cerebral artery occlusion-induced stroke in mice.
Stroke is the third leading cause of death and the leading cause of long-term disability in North America. On average, someone in the US has a stroke every 45 s, and worldwide, stroke claims 15 million lives each year. Therefore, reliable stroke models are vital to the production of effective new therapies for the treatment of this devastating cerebral vascular accident. Middle cerebral artery occlusion (MCAo) is considered to be the most clinically relevant surgical model of ischemic stroke, in which a variety of methods may be employed to block the MCA (the most common being through insertion of a monofilament). In this study, we have compared two different approaches that are currently used arbitrarily in various laboratories worldwide: one involving insertion of a monofilament via the common carotid artery (Koizumi et al.) and one via the external carotid artery (Longa et al.). We assessed various parameters, including: mortality rates, neurological scores, inflammation levels, cellular trafficking (using intravital microscopy) and infarct volumes in mice after using each of the two approaches. We found that the Longa method produced a greater, and robust, inflammatory response, versus the Koizumi method. In conclusion, we suggest that the Longa method is superior for the study of both short and long-term outcomes of ischemic stroke. These results have considerable implications on stroke model selection for researchers.


Lysosomal enzymes in bovine mammary leukocytes during the nonlactating period.
Leukocytes from mammary secretions in dairy cows were collected during the nonlactating and postpartum periods. Differential cell counts, viability and activity of peroxidase, N-acetyl-beta-D-glucosaminidase (NAGase, beta-glucuronidase and alpha-mannosidase in cells were determined. Cell viability (trypan blue exclusion) was 75-80% during most of the nonlactating period, but declined to 45-50% by parturition. Polymorphonuclear neutrophils (PMN) predominated during the first week of involution, after which macrophages were the predominant cell type. Peroxidase activity in leukocytes from mammary secretions was high in early involution, probably reflecting the predominant peroxidase-containing PMN. Peroxidase activity declined through the remaining nonlactating and postpartum periods. The activity of NAGase was variable in early involution, then increased to a peak during the mid-nonlactating period, before declining prior to parturition. Activity of beta-glucuronidase generally was unchanged during the nonlactating period, although NAGase and beta-glucuronidase activities were significantly and positively correlated throughout the period studied. Activity of alpha-mannosidase changed in a manner similar to peroxidase activity.


Immunoelectronmicroscopic investigation of Hodgkin's disease with monoclonal antibodies against histiocytes.
8 cases of Hodgkin's disease (HD nodular sclerosis (n = 3), HD mixed type (n = 2), and nodular paragranuloma (n = 3] were investigated with monoclonal antibodies against histiocytes (Ki-M1, Ki-M3, Ki-M4, Ki-M6, and Ki-M7). Reactivity of H- and SR-cells with the monoclonal antibodies Ki-M3 and Ki-M7 could be shown at the ultrastructural level in cases of HD of nodular sclerosis and mixed type. In nodular paragranuloma no positive H-, SR- nor L & H-cells could be demonstrated. The reaction site of the monoclonal antibodies in H- and SR-cells was comparable to those in histiocytes.


Allele frequency and genotype distribution of polymorphisms within disease-related genes is influenced by ethnic population sub-structuring in Sudan.
Four single nucleotide polymorphisms (SNPs) and a variable number of tandem repeats (VNTR) polymorphism located within disease associated/causing genes were typed in four populations of different tribal and ethnic affiliation from the Sudan. The genotype and allele frequencies were compared with those of other groups from published and unpublished data of world populations. The combined Sudanese sample conformed with Hardy-Weinberg equilibrium (HWE) expectation. However, population sub-structuring according to ethnic/linguistic group indicated at least two SNPs in departure from HWE. Differences in allele frequencies and genotype distribution between groups was also noted in three of the four SNPs. The other loci were distributed homogeneously within the populations studied with genotype frequencies in agreement with HWE expectation. These results highlight the importance of inter-population stratification for polymorphic markers, as well as the potential influence of evolutionary history and ethnic variation of loci, in the general distribution of SNPs and other polymorphisms.


Signal intensity loss of the intervertebral discs in the cervical spine of young patients on fluid sensitive sequences.
To evaluate the signal intensity (SI) of the intervertebral discs of the cervical spine on magnetic resonance (MR) fluid sensitive sequences, and correlate this to secondary signs of degeneration on MR and radiographs as well as to age. A total of 265 patients aged ≥16 with back pain (≥3-months, <2-year, onset <45-years) from the SPondyloArthritis Caught Early (SPACE) cohort were included. Sagittal 1.5 T MR images and lateral radiographs of the cervical spine were independently evaluated by two readers for: SI of the intervertebral discs using a grading system based of Pfirrmann (grade 1 normal/bright SI; 2 inhomogeneous/bright SI; 3 inhomogeneous/mildly decreased SI; 4 inhomogeneous/markedly decreased SI; 5 signal void), disc herniation and Modic changes (MRI) and disc space narrowing, osteophytes and sclerosis (radiograph). Readers were blinded for clinical information. Descriptive statistics were used for characteristics and prevalence of findings, and regression analysis was used for age and grades. Of 265 patients (36% male, mean age 30), 221 (83%) patients had 1 to 6 discs (median 4) with decreased SI. Of 1,590 discs, 737 (46%) were grade 1; 711 (45%) grade 2; 133 (8%) grade 3; 8 (1%) grade 4 and 1 (0%) grade 5. Secondary signs of degeneration were rare and seen predominantly in C5-C7 and appear to be related to signal loss grade 3 and 4. Low signal intensity of intervertebral discs in absence of secondary degenerative signs in the cervical spine on fluid sensitive MR images might be pre-existing and part of the natural course.


Effect of Hypericum humifusum aqueous and methanolic leaf extracts on biochemical and histological parameters in adult rats.
Hypericum genus is traditionally known for its medicinal use and its therapeutic and antioxidant effects. However, the toxic effect of this plant has not been much explored. Our study aimed at investigating the effect of Hypericum humifusum (Hh) leaf extracts on oxidative stress parameters in male rats. For it, we first focused on the phytochemical analysis of the aqueous and methanolic extracts of Hh leaves. Hence, Wistar rats were treated per gavage for 30 days and divided into Control (1 mL/rat, distilled water), A200 group (200 mg/kg body weight (bw) aqueous extract), A400 group (400 mg/kg bw aqueous extract), M10 group (10 mg/kg bw methanolic extract), M20 group (20 mg/kg bw methanolic extract). The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. Biochemical and histological investigations were performed in plasma and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels. At the same time, alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) were assayed in plasma samples. Histological study was also conducted in liver. We showed that Hh extracts reduced relative liver weight and increased ALT, AST, LDH activities in treated groups compared to control group. These results were associated with an increase of MDA levels and a decrease of antioxidant enzyme activities (CAT and SOD) in liver tissues of treated rats. Histology of liver demonstrated several alterations showing necrosis, altered hepatocytes and lymphocyte migration mainly in A200 group and dilated sinusoids, foamy appearance of hepatocytes and lymphocyte accumulation in the other treated groups. This original work indicated that chronic consumption of Hh leaf extracts has no antioxidant effect but instead it induces oxidative stress and enhances markers of cell damage which was confirmed by histological study of liver rats.


Logistic regression analysis of risk factors for prolonged pulmonary recovery in children from aspirated foreign body.
Foreign body aspiration is a life-threatening emergency for children. Fried chicken is commonly available all over the world, but no cases have previously been reported addressing this food as a tracheobronchial foreign body. We report an extremely rare case of tracheobronchial aspiration of fried chicken complicated by severe bronchitis and postoperative atelectasis. To clarify predisposing factors related to bronchopulmonary complications, we also reviewed paediatric cases of tracheobronchial foreign bodies treated in our department over the past 14 years. We retrospectively reviewed a total of 77 cases of tracheobronchial foreign bodies from 1988 to 2011. The main outcome measure was duration of hospitalisation, reflecting postoperative therapy. Logistic regression analyses were conducted to determine risk factors for longer hospitalisation. Age, sex, and interval between the aspiration episode and bronchoscopy were not significantly associated with longer hospitalisation. Regarding kinds of foreign bodies, higher rates of longer hospitalisation were noted for patients who had aspirated peanut or animal material, as compared to patients who had aspirated non-organic material (odds ratio, 5.80; 95% confidence interval, 1.12-30.43). In terms of predicting the risk of pulmonary complications, the type of foreign body aspirated offers a more meaningful factor than the interval between aspiration and operation. Specifically, peanuts or animal material containing oils appear to be associated with a more prolonged pulmonary recovery even after retrieval of the foreign body.


The role of gene-ambient air pollution interactions in paediatric asthma.
Globally, asthma prevention and treatment remain a challenge. Ambient air pollution (AAP) is an environmental risk factor of special interest in asthma research. AAP is poorly defined and has been subdivided either by the origin of the air pollution or by the specific bioactive compounds. The link between AAP exposure and asthma exacerbations is well established and has been extensively reviewed. In this narrative review, we discuss the specific genetic variants that have been associated with increased AAP sensitivity and impact in paediatric asthma. We highlight the relative importance of variants associated with genes with a role in oxidant defences and the nuclear factor-κB pathway supporting a potential central role for these pathways in AAP sensitivity.


Neural stem cell therapy for neurovascular injury in Alzheimer's disease.
Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration leading to severe cognitive decline and eventual death. AD pathophysiology is complex, but neurotoxic accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau are believed to be main drivers of neurodegeneration in AD. The formation and deposition of Aβ plaques occurs in the brain parenchyma as well as in the cerebral vasculature. Thus, proper blood-brain barrier (BBB) and cerebrovascular functioning are crucial for clearance of Aβ from the brain, and neurovascular dysfunction may be a critical component of AD development. Further, neuroinflammation and dysfunction of angiogenesis, neurogenesis, and neurorestorative capabilities play a role in AD pathophysiology. Currently, there is no effective treatment to prevent or restore loss of brain tissue and cognitive decline in patients with AD. Based on multifactorial and complex pathophysiological cascades in multiple Alzheimer's disease stages, effective AD therapies need to focus on targeting early AD pathology and preserving cerebrovascular function. Neural stem cells (NSCs) participate extensively in mammalian brain homeostasis and repair and exhibit pleiotropic intrinsic properties that likely make them attractive candidates for the treatment of AD. In the review, we summarize the current advances in knowledge regarding neurovascular aspects of AD-related neurodegeneration and discuss multiple actions of NSCs from preclinical studies of AD to evaluate their potential for future clinical treatment of AD.


Single-crossover dynamics: finite versus infinite populations.
Populations evolving under the joint influence of recombination and resampling (traditionally known as genetic drift) are investigated. First, we summarize and adapt a deterministic approach, as valid for infinite populations, which assumes continuous time and single crossover events. The corresponding nonlinear system of differential equations permits a closed solution, both in terms of the type frequencies and via linkage disequilibria of all orders. To include stochastic effects, we then consider the corresponding finite-population model, the Moran model with single crossovers, and examine it both analytically and by means of simulations. Particular emphasis is on the connection with the deterministic solution. If there is only recombination and every pair of recombined offspring replaces their pair of parents (i.e., there is no resampling), then the expected type frequencies in the finite population, of arbitrary size, equal the type frequencies in the infinite population. If resampling is included, the stochastic process converges, in the infinite-population limit, to the deterministic dynamics, which turns out to be a good approximation already for populations of moderate size.


Ifosfamide-induced neurotoxicity: associated symptoms and nursing implications.
To review current understanding of the neurotoxicity associated with ifosfamide administration. Published studies of ifosfamide-induced neurotoxicity, published literature on other causes of neurotoxicity associated with cancer, and a case study. Ifosfamide-induced neurotoxicity has not been well-described in the nursing literature. To correctly identify ifosfamide-induced neurotoxicity, nurses need to assess the patient's history and neurologic, affective, and cognitive status and implement appropriate nursing interventions. Research aimed at accurate identification of ifosfamide-induced neurotoxicity and the most effective nursing interventions is needed. Judicious nursing assessment will facilitate differentiation of ifosfamide-induced neurotoxicity from other neurotoxicities associated with cancer and its treatment.


HLA typing and karyotyping of limited numbers of lymphocytes is facilitated by in vitro expansion with TCGF.
It is often difficult to obtain sufficient quantities of leukocytes from bone marrow (BM) transplant recipients for post-transplant immunological monitoring and evaluation of engraftment. We have developed a cell culture expansion technique that allows HLA-A,B, and DR typing as well as karyotyping on limited numbers (less than 10(7)) of lymphocytes. Lymphocytes from healthy control donors were allo-activated in vitro and further expanded by culturing in T-cell growth factor (TCGF). After 14 days of culture, these cells were sent for blind HLA-A,B and DR typing and for karyotyping. Surface marker studies showed that 90% of the T-cells expanded in growth factor are OK-la positive. HLA typing with these DR-bearing in vitro expanded T-cells showed excellent correlation with HLA typing on fresh unexpanded lymphocytes. Karyotyping of expanded T-cells showed normal male or female cells as expected. This technique may be especially valuable when testing pediatric or adult patients with very low lymphocyte counts.


Drug-protein conjugates--XVI. Studies of sorbinil metabolism: formation of 2-hydroxysorbinil and unstable protein conjugates.
The metabolism of sorbinil [+)6-fluoro-spiro (chroman-4, 4'-imidazolidine)-2',5' dione), an aldose reductase inhibitor associated with immunological adverse reactions, was studied in vivo and in vitro with particular reference to the formation of protein conjugates of 2-hydroxysorbinil and their further metabolism. [8-3H]Sorbinil was rapidly and extensively metabolized in the rat. 2-Hydroxysorbinil (2HSB) and a phenolic primary alcohol (2,4-imidazolidinedione 5-(2-hydroxyethyl)-5-(5-fluoro-2-hydroxyphenyl); IHFH) were its principal urinary metabolites; over 0-24 hr, they represented 17.0 +/- 0.7% (mean +/- SD, N = 4) and 7.1 +/- 0.7% of the dose, respectively. [3H]2HSB isolated from urine and re-administered was converted to IHFH. Chronic dosing with sorbinil (150 mg/kg x 5) induced 2-hydroxylation of the drug, the 0-24 hr urinary excretion of 2HSB increasing from 17.0 +/- 0.7% to 24.7 +/- 3.4% of the dose (P less than 0.05 by Students' paired t-test). The biotransformation of 2HSB to IHFH was rationalized in terms of an open-chain aldehyde intermediate. Since aldehydes form both stable and unstable protein adducts, 2HSB was potentially a pro-reactive metabolite and initiator of the hypersensitivity reaction associated with sorbinil. However, [3H]2HSB was neither metabolized by human liver microsomes nor underwent irreversible binding to the microsomal protein. Nevertheless, the mild reductant sodium cyanoborohydride, although without effect on microsomal binding of [3H]2HSB, enhanced binding to human serum albumin. Formation of unstable Schiff base adducts was indicated.


[Tensile strength of partially cut lateral knee ligaments following, or without plaster immobilization].
The tension strength of partially cut medial collateral ligaments of rabbits was higher after functional treatment than after casting. Therefore we conclude, that functional therapy after surgical treatment recommeneded by Burri et al. (3) has a beneficial effect on tension strength of human collateral ligaments.


New distribution records for Canadian Aleocharinae (Coleoptera, Staphylinidae), and new synonymies for Trichiusa.
Fifty-four new Canadian provincial records of aleocharine beetles (Staphylinidae), including three new Canadian records and one new North American record, are presented. Of these, 33 are new provincial records for Saskatchewan, 14 for Alberta, two for British Columbia, three for Manitoba, two for the Northwest Territories and one for the Yukon Territory. The following are new Canadian records: Trichiusapilosa Casey [formerly reported from Nova Scotia and Ontario as Trichiusapostica Casey], Acrotonarecondita (Erichson) and the adventive Palaearctic Athetanigra (Kraatz), which is also a new North American record. Bionomics information and new locality records are provided. The following new synonyms of Trichiusapilosa Casey are established: Trichiusaatra Casey, Trichiusamonticola Casey, Trichiusaparviceps Casey, and Trichiusapostica Casey. The numbers of Aleocharinae remaining to be discovered in Canadian provinces and territories are discussed.


Endoscopic Sealing With a Polyglycolic Acid Sheet for Restoration of Vocal Fold Mucosa in Dogs.
Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet. Animal experiment. Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA-bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high-speed camera, and histological analysis was performed. The re-epithelialization process was delayed in the PGA and PGA-bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA-bFGF groups compared with the control group. The PGA-bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA-bFGF and control groups. The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects. NA Laryngoscope, 130:E436-E443, 2020.


Relationship between nuclear chromatin decondensation (NCD) in vitro and other sperm parameters and their predictive value on fertilization rate in IVF program.
The purpose of this study was to determine the in-vitro induced nuclear chromatin decondensation (NCD) of human spermatozoa and its value in combination with routine semen analysis in predicting the outcome of in-vitro fertilization (IVF). The ejaculate of 52 couples, undergoing IVF, was incubated with lithium diidosalicylic acid (LIS) and dithiothreitol (DTT) (G.1) or with heparin and sodium dodecyl sulphate (SDS) (G.2) to induce chromatin decondensation (NCD). Smears were made at 30, 60, and 120 min after incubation. NCD was evaluated by morphometrical detection of the surface area of the spermatozoa using a semiautomatic image analysis system (IBAS). In both groups, the sperm heads showed a significant enlargement after 30, 60, and 120 min incubation in comparison to the initial size. However, no correlation was found between NCD at various periods of time and the fertilization rates. The mean area of the sperm heads in the native sample in the G.1 was 9.45+/- 1.33 microm(2) and 9.02+/- 1.15 microm(2) in the G.2. This area increased after incubation for 30, 60, and 120 min to 10.92 +/- 1.48, 12.26+/- 2.16, 13.54+/- 3.14, and 15.35+/- 7.78 microm(2) in the first group (G.1) and to 10.29 +/- 1.15, 11.23 +/- 1.85, 11.46 +/- 1.97, and 11.27 +/- 2.82 microm(2) in the second group, respectively. NCD in vitro after incubation with LIS + DTT or heparin + SDS could not be recommended as a predictive parameter for IVF outcome.


Chromosomal aberrations in heavy smokers.
Lymphocyte chromosomes from 20 heavy smokers were analyzed from 48-h whole blood cultures for the frequency of dicentric chromosomes, ring chromosomes, and chromatid translocations. Compared to controls, these exchange type aberrations occurred more frequently in the smokers.


A colloidal assembly approach to synthesize magnetic porous composite nanoclusters for efficient protein adsorption.
A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation.


Nitrogen and carbon flows between the caecum, blood and rumen in sheep given chopped lucerne (Medicago sativa) hay.
1. Experiments involving 15N and 14C tracers were made in sheep consuming 800 g air-dry chopped lucerne (Medicago sativa) hay/d and providing 20.4 g N/d to study N and C flows within the caecal digesta and between the caecum, blood and rumen. 2. Continuous infusions of 15N tracers were made into the caecal ammonia, blood urea and rumen NH3 pools. The concentration and enrichment of caecal digesta NH3-N, caecal microbial N, caecal digesta non-urea, non-ammonia-N (NU-NAN), faecal NU-NAN, blood urea-N, rumen digesta NH3-N and rumen bacterial N were estimated at intervals during the infusions. A three-pool open-compartment model was solved to estimate N flows between the caecal digesta NH3-N, blood urea-N and rumen digesta NH3-N pools. 3. The rate of irreversible loss from the caecal digesta NH3-N pool was 2.17 (SE 0.623) g N/d. On average 0.9 (SE 0.56) g N/d of caecal digesta NH3-N was derived from blood urea and 0.1 (SE 0.08) g caecal digesta NH3-N/d was apparently derived from the fermentation of undigested rumen microbes in the caecum. The amount of NH3-N produced by proteolysis and deamination of dietary and endogenous N was 1.1 (SE 0.13) g/d. 4. There was net incorporation of 0.56 (SE 0.306) g caecal digesta NH3-N/d into caecal microbes. The microbial N synthesized de novo in the caecum was not determined, but 2.9 (SE 0.52) g microbial N/d of both rumen and caecal origin flowed out of the caecum and constituted 0.48 of the NU-NAN flow. The majority (mean 0.83 (SE 0.044] of this microbial N was excreted in faeces. 5. On average 1.8 (SE 0.80) g caecal digesta NH3-N/d were absorbed. Of this NH3-N, 0.92 (SE 0.054) was converted to blood urea, contributing 0.10 (SE 0.031) of blood urea-N. Only 0.012 (SE 0.0041) of rumen digesta NH3-N and 0.005 (SE 0.0009) of rumen bacterial N were derived from caecal digesta NH3-N. 6. Infusions of 14C tracers were made into the caecal digesta bicarbonate, blood bicarbonate, rumen digesta bicarbonate and blood urea pools, and samples were obtained at intervals to determine the specific radioactivity of each pool. A four-pool open-compartment model was solved to estimate C flows between these pools. 7. The rate of irreversible loss of blood urea estimated with [14C]urea (17.1 (SE 1.18) g N/d) was greater (P less than 0.01) than that estimated with [15N]urea (14.0 (SE 0.87) g N/d).(ABSTRACT TRUNCATED AT 400 WORDS)


Longitudinal study on diffusion tensor imaging and diffusion tensor tractography following spinal cord contusion injury in rats.
Diffusion tensor imaging (DTI) as a potential technology has been used in spinal cord injury (SCI) studies, but the longitudinal evaluation of DTI parameters after SCI, and the correlation between DTI parameters and locomotor outcomes need to be defined. Adult Wistar rats (n = 6) underwent traumatic thoracic cord contusion by an NYU impactor. DTI and Basso-Beattie-Bresnahan datasets were collected pre-SCI and 1, 3, 7, 14, and 84 days post-SCI. Diffusion tensor tractography (DTT) of the spinal cord was also generated. Fractional anisotropy (FA) and connection rate of fibers at the injury epicenter and at 5 mm rostral/caudal to the epicenter were calculated. The variations of these parameters after SCI were observed by one-way analysis of variance and the correlations between these parameters and motor function were explored by Pearson's correlation. FA at the epicenter decreased most remarkably on day 1 post-SCI (from 0.780 ± 0.012 to 0.330 ± 0.015), and continued to decrease slightly by day 3 post-SCI (0.313 ± 0.015), while other parameters decreased significantly over the first 3 days after SCI. DTT showed residual fibers concentrated on ventral and ventrolateral sides of the cord. Moreover, FA at the epicenter exhibited the strongest correlation (r = 0.887, p = 0.000) with the locomotion performance. FA was sensitive to degeneration in white matter and DTT could directly reflect the distribution of the residual white matter. Moreover, days 1 to 3 post-SCI may be the optimal time window for SCI examination and therapy.


An antifeedant in balsam poplar inhibits browsing by snowshoe hares.
The 'plant defense guild' hypothesis for the evolution of plant secondary chemicals predicts that plant species defend themselves against generalist herbivores such as the snowshoe hare (Lepus americanus) in the Canadian boreal forest by evolving unique antifeedant chemicals. Plant species may coevolve in an ecosystem by presenting an array of chemicals to herbivores. We report further evidence for this idea from the presence of 2,4,6-trihydroxydihydrochalcone in the CH2Cl2 extracts of Populus balsamifera juvenile twigs. These extracts, added to rabbit chow, were offered to hares in choice tests. The bioassay established that the chemical acted as an antifeedant for hares.


Modern treatment of pulmonary embolism.
Pulmonary embolism is diagnosed over 100,000 times yearly in the United States and is the recognized primary cause of death in at least 10,000 cases. Thrombolytic therapy has been successful in reducing clot burden substantially; however, clinical data are lacking to indicate that thrombolytic therapy improves mortality rates in patients with pulmonary emboli or that the pharmacologic removal of clot will improve future quality of life. The use of thrombolytic agents has been limited by the potential for producing hemorrhagic complications. This paper discusses the pharmacology of numerous thrombolytic agents and their clinical use in research studies intended to determine the safest and most efficacious regimens. Recombinant t-PA infusions appear quite safe and produce very rapid lyses of pulmonary emboli. Innovative administration regimens of urokinase also appear promising. The availability of extremely safe and efficacious treatment regimens should allow for large epidemiologic studies to be conducted to determine whether thrombolytic therapy will improve the morbidity and mortality of pulmonary embolism.


Purification and characterization of the Ca2+/calmodulin-dependent protein kinase II from chicken forebrain.
CaM kinase II is known to be enriched in mammalian and avian brains. To determine the holoenzymic composition and functional characteristics of this kinase, a new approach for isolation was applied to isolate it from the chicken forebrain. Forebrains of hatched 45-d chicken were dissected, homogenized, and centrifuged. The supernatant was loaded onto a CaM-agarose affinity column and the calmodulin-binding proteins were eluted with EGTA. Selected eluates were loaded onto the antibody-agarose affinity column, which was prepared with monoclonal antibody (MAb) (6G9) to the CaM kinase II alpha subunit. Samples were subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and either silver-stained or blotted onto a nitrocellulose membrane. The protein composition and the immunoreactivity of the antibody-agarose affinity eluate fractions were analyzed with a densitometric scanner. Silver staining of gels showed that the beta subunit doublet, the beta' subunit, and a putative substrate were coeluted with the alpha subunit from the antibody affinity column although only the alpha subunit bound the 6G9 antibody. Scintillation counting showed that the autophosphorylation of the kinase was significantly reduced in the eluate from the antibody affinity column. Whereas silver staining indicated an increase in the relative amount of alpha subunit had occurred during purification, phosphorylation assays indicated an increase in the relative amount of the alpha subunit after the last purification step. A possible reason for this is discussed. The presence of beta/beta' subunits in the antibody-agarose affinity eluate indicated the existence of an alpha beta/beta' heteropolymer. The phosphorylation assay was not a good indication of the amount of purification because of the loss of enzyme activity following purification. In contrast, the immunoassay indicated a 97-fold purification from the cytosolic fraction was achieved using the method. In conclusion, the data indicate the existence of the CaM kinase II alpha beta/beta' heteropolymer in the chicken forebrain.


Evidences of Reduced Antioxidant Activity in Patients With Chronic Migraine and Medication-Overuse Headache.
Migraine is a complex multifactorial, neurobiological disorder, whose pathogenesis is not fully understood, nor are the mechanisms associated with migraine transformation from episodic to chronic pattern. A possible role of impaired oxidative mitochondrial metabolism in migraine pathogenesis has been hypothesized, and increased levels of peripheral markers of oxidative stress have been reported in migraine patients, although the literature data are limited and heterogeneous. The aim of this cross-sectional study was to determine plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power and total plasmatic thiol groups, all plasmatic markers related to oxidative stress, in a sample of chronic migraine patients and medication-overuse headache, compared to a control group of healthy subjects. Thirty-three patients with a diagnosis of both chronic migraine and medication-overuse headache (International Classification of Headache Disorders,3rd edition, beta version) and 33 healthy, headache-free subjects were enrolled. Patients with comorbid/coexisting conditions were excluded, as well as patients in treatment with migraine preventive drugs. Plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power, and total thiol groups were determined in migraine patients and controls; moreover, oxidative stress biomarkers were compared in migraine patients with triptan compared to non-steroidal anti-inflammatory drug overuse. The statistical analysis showed significantly lower levels of ferric-reducing antioxidant power and total plasmatic thiol groups, both expression of antioxidant power, in patients with chronic migraine and medication-overuse headache compared to controls (respectively, ferric antioxidant power median [interquartile range] 0.53 [0.22] vs 0.82 [0.11] mmol/L, P < .001; total thiol groups 0.25 [0.08] vs 0.51 [0.11] μmol/L, P < .001). Moreover, no statistically significant differences in oxidative stress biomarkers were detected between patients with triptan and nonsteroidal anti-inflammatory drug overuse. The data from the present study suggest that antioxidant capacity is lower in chronic migraine patients and medication-overuse headache compared to healthy headache-free subjects, with no differences between patients with triptan or nonsteroidal anti-inflammatory drug overuse. Further investigation is certainly necessary in order to define the causal or consequential role of an imbalance between pro-oxidants and antioxidant defenses in migraine pathogenesis and "chronification" and the possible therapeutic implications in clinical practice.


Exploring the Predictive Value of Gambling Motives, Cognitive Distortions, and Materialism on Problem Gambling Severity in Adolescents and Young Adults.
Gambling motives and cognitive distortions are thought to be associated because both coping and financial motives to gamble appear to be predictors of gambling related cognitive distortions. Therefore, there is an argument to be made that gambling motives, cognitive distortions, and materialism share common attributes and might be related to problem gambling severity. The present paper aims to examine the relationship between these three variables, both in a clinical and community setting, to see if they can predict gambling severity. A sample of 250 participants from the general population and 31 participants from the clinical population was recruited. The results showed that the clinical sample scored higher on gambling severity, cognitive distortions, materialism, and gambling motives. It also showed that low scores in enhancement motives and higher scores in social motives and gambling related cognitions predicted gambling severity in older gamblers, whereas for younger patients, gambling severity was best predicted by higher scores in materialism and coping motives, and lower scores for enhancement and social motives. In the community sample, gambling severity correlated with gambling related cognitive distortions and with gambling motives (except for social and coping motives within the women subsample). These results testify to the importance of materialism, cognitive distortions, and gambling motives as risk factors for problem gambling both in community and clinical samples.


Enhancement of apoptosis via an extrinsic factor, TNF-alpha, in cells infected with cytopathic bovine viral diarrhea virus.
Isolates of bovine viral diarrhea virus (BVDV) are divided into cytopathic (cp) and noncytopathic (ncp) biotypes according to their effect on cultured cells. Calves persistently infected with ncp BVDV are known to develop lethal mucosal disease (MD) after superinfection by cp BVDV. Although the UV-irradiated supernatant of cp BVDV-infected cells has been reported to have no capacity to induce cell death, we found that it could enhance cell death through apoptosis. Up-regulation of tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) mRNAs was detected specifically in cp BVDV-infected primary cell cultures. Suppression of TNF-alpha via antisense oligonucleotide transfection or incubation with a polyclonal antibody against TNF-alpha resulted in attenuation of apoptosis induced by cp BVDV, suggesting that TNF-alpha participates in apoptosis execution. Although TNF-alpha is one of the iNOS-inducible factors, the iNOS up-regulation was not regulated by TNF-alpha. And iNOS was revealed to serve as anti-apoptotic factor, contrary to our expectation. In addition, the expression level of both TNF-alpha and iNOS mRNAs in the ncp BVDV-infected cells was kept lower than that in the mock-infected cells, suggesting that ncp BVDV reduced or interfered with the factor triggering the expression of both mRNAs. These characteristic mRNA transcriptions would help to explain why BVDV acts differently in cells as well as in vivo, depending on its biotype. To elucidate viral factors inducing TNF-alpha and iNOS may be critical to understand the mechanism of MD development, which closely correlates with cp BVDV-induced apoptosis.


RNA virus expression during and after methylnitrosourea-induced T-cell leukemogenesis in mice.
The expression of RNA tumor virus was studied in BDF 1 mice after leukemogenic treatment with a single dose of methylnitrosourea (MNU) and in leukemic thymuses by a cell ELISA using antibodies against the viral glycoprotein gp 70 and by co-culture for the detection of eco- and xenotropic virus. The majority of the thymomas were positive for gp 70; ecotropic, but not xenotropic infectious virus could be detected in some of them. Early after MNU application the thymus and the bone marrow were positive for gp 70 in some animals. Later, after a phase with positive results with spleen cells, the bone marrow and the spleen were negative again. Only the thymus of some mice were positive during the last weeks before the first leukemias appeared.


A Novel Technique for Cervical Microscopic Foraminotomy Utilizing Spinous Process Splitting: Microscopic Mini-Open Foraminotomy.
In this study, we present "microscopic mini-open foraminotomy (MicroMOF)" as a new, less invasive method for posterior cervical foraminotomy. Using surgical microscope guidance, the spinous process is hemi-split, and the posterior muscle is detached from the laminar subperiosteal surface. Bony resection is then performed obliquely from medial posterior to lateral anterior under lateral-tilted surgical field exposure. MicroMOF has been performed successfully for cervical radiculopathy and cervical spondylotic amyotrophy, which achieved postoperative symptom improvement with few complications. The novel MicroMOF foraminotomy technique has been found to protect the nerve root and vertebral artery and help preserve muscle and cervical facet joint bone.


Age-dependent gene induction in quail oviduct. IX. Age-dependent alterations of DNA-bound amino acids.
DNA-amino acids (and DNA-protein) complexes were isolated from oviducts of immature, mature and senescent quails by a procedure which does not involve proteolytic enzymes. The content of DNA-amino acids in the complexes, isolated from animals belonging to three different age classes is almost identical and it amounts to about 10 micrograms/mg DNA. However, the fraction of DNA-amino acids which is resistant to pronase is twice as high in lysates from senescent quails as in those from immature and mature animals. The amount of DNA-bound amino acids is strongly dependent on hormone-induced physiological effects in immature quails. If immature animals were treated with estrogen hormone, which causes in induction both of DNA and RNA synthesis, the level of DNA-bound amino acids increases by 220%. This material has been found to be pronase sensitive which might indicate that the amino acids are present as peptides. Treatment of estrogen-stimulated animals with progesterone or inhibitors of DNA and RNA synthesis antagonizes the estrogen-envoked formation of DNA-associated amino acids. From the data we propose that the amount of proteins and/or amino acids, bound to DNA,is not only age-related but also correlated with the physiological state of DNA in immature and mature animals.


Lupeol: A Triterpenoid Isolated from the Stem Bark of Hymenocardia Acida (tul.) Exhibits a van der Waal Antagonism on the Alpha Subunit of Gastric H+K+Atpase - A Promising Antiulcer Principle.
Hymenocardia acida (HA) is one of the numerous medicinal plants in Nigeria with ethnomedicinal history of usage in the treatment of ulcer. The study aimed at isolating antiulcer principle(s) from the stem bark of HA as well as the mechanism of action determination. Antiulcer screenings of the crude extract, aqueous fraction, and bulked VLC fractions were performed using in vivo and in vitro models. Docking was carried out by using PyRx. Crude extract (HA; 1 mg/mL) and the aqueous fraction of H. acida (HAA; 1 mg/mL) showed an acid neutralizing capacity (MEq) of 0.3948 and 0.4035, respectively which is significantly different from 0.431 MEq showed by negative control (distilled water) at p<0.05. BVLC 3 (1 mg/mL) showed a significant value of 0.4049 MEq. However, HA showed a dose-dependent decrease in activity across doses examined, with 100 mg/kg showing an ulcer index of 10.00±2.89 (61.50%) and cimetidine (positive control; 100 mg/kg), also showed the highest ulcer index of 3.67±0.88 (85.9%), which is significantly different from ulcer index of 26.00±6.35 (0.00%) p<0.05 observed in the negative control (5% dimethylsulphoxide). The highest ulcer index of 8.00±1.32 (65.10%) was noted in BVLC 3. Bioactive BVLC 3, resulted in an isolated compound (BF3B2A). The compound was suggested to be lupeol, with a docking score of -7.7. It showed a van der Waal interaction with some key amino acid residues in the vonoprazan binding site. The experimental studies justify the ethnomedicinal claim of usage among locals.


Leiomyomatous hamartoma: report of two cases and review of the literature.
Two cases of leiomyomatous hamartoma (LH) in patients of Latin ancestry are reported here. The first lesion was detected on the incisive papilla of a 19-year-old woman; this is an unusual age because these lesions are commonly observed during the first years of life. The second lesion found on the middle-dorsum of the tongue was observed in a 5-month-old boy. The diagnosis was based on the histopathological appearance and confirmed by immunohistochemistry with positivity for smooth muscle actin, muscle-specific actin, S-100 protein and desmin. To date, only 16 cases have been reported in the English-language literature. Controversial epidemiological data, histogenesis, clinical/histopathological features, and differential diagnosis are discussed herein.


Multichannel strain gauge telemetry for orthopaedic implants.
In vivo measurements of the loads and deformations occurring in orthopaedic implants will allow future improvements to be made. This paper describes an extremely small telemetry for long term measurements with three strain gauges and methods for an absolutely safe implant design. Developed for measuring the load at hip prostheses, the telemetry can also be used for other implants. Its size makes feasible instrumentation of devices with only slight mechanical modifications. In addition to the description of our own measuring system, the paper gives a survey on the problems of telemetrized implants, on methods for measuring spatial loads, and on the investigations of other authors. Future publications will present in vivo measurements with this telemetry, among others on hip endoprostheses.


Three case reports of behavioral disinhibition with clonazepam.
Recent reports have supported the innovative use of clonazepam in the treatment of various psychiatric conditions. This report alerts clinicians that, although helpful in some patients, clonazepam can cause behavioral disinhibition and worsening of symptoms in other patients.


How single-trial electrical neuroimaging contributes to multisensory research.
This study details a method to statistically determine, on a millisecond scale and for individual subjects, those brain areas whose activity differs between experimental conditions, using single-trial scalp-recorded EEG data. To do this, we non-invasively estimated local field potentials (LFPs) using the ELECTRA distributed inverse solution and applied non-parametric statistical tests at each brain voxel and for each time point. This yields a spatio-temporal activation pattern of differential brain responses. The method is illustrated here in the analysis of auditory-somatosensory (AS) multisensory interactions in four subjects. Differential multisensory responses were temporally and spatially consistent across individuals, with onset at approximately 50 ms and superposition within areas of the posterior superior temporal cortex that have traditionally been considered auditory in their function. The close agreement of these results with previous investigations of AS multisensory interactions suggests that the present approach constitutes a reliable method for studying multisensory processing with the temporal and spatial resolution required to elucidate several existing questions in this field. In particular, the present analyses permit a more direct comparison between human and animal studies of multisensory interactions and can be extended to examine correlation between electrophysiological phenomena and behavior.


[Subtrochanteric fractures].
Subtrochanteric fractures represent a distinct entity. They are different from proximal femoral fractures as well as femoral shaft fractures. Nowadays, these fractures are mainly found in the geriatric population. Fractures in younger patients are indicative of high-energy trauma. Comorbidities are important in the geriatric population whereas accompanying injuries are most important in younger patients. Early surgical stabilization of subtrochanteric fractures is the treatment of choice, which under certain circumstances should also be carried out within the framework of damage control orthopedics. Long cephalomedullary nails represent the standard procedure. In geriatric patients the primary aim is weight bearing stability. The risk of complications with subtrochanteric fractures in the literature is relatively high. Classical compression plates play a role in the management of complications.


Characterization of bioactives and in vitro biological activity from Protaetia brevitarsis larval extracts obtained by different pretreatment extractions.
Intestinal contents affect the characterization of edible insect bioactive compounds. Two empty intestine methods, namely, traditional static method (TSM) or salt immersion stress method (SISM), associated with extraction solvents water (W), 50 % water-ethanol (W:E) or 100 % ethanol (E), were used to obtain six Protaetia brevitarsis larval extracts. The total flavonoid content (TFC) in the W:E extracts was significantly higher than that in the W and E extracts, with TSM-W:E the highest (p < 0.05). The relative contents of 132 bioactive compounds, especially p-hydroxyphenylacetic acid, citric acid, and dehydroepiandrosterone, were different between TSM-W and SISM-W. TSM-W:E had significantly higher 2,2-diphenyl-1-picrylhydroxy· (DPPḢ) scavenging and pancreatic lipase (PL) inhibitory activity than SISM-W:E (p < 0.05). DPPḢ scavenging and PL inhibitory activities were highly correlated with TFC and carbohydrates, respectively. Thus, bioactive compounds in P. brevitarsis extracts can be obtained selectively using pretreatment methods, which might be beneficial for high-value utilization of P. brevitarsis.


A 1.5V 120nW CMOS programmable monolithic reference generator for wireless implantable system.
We implement and characterize a 1.5 V 120 nW CMOS programmable monolithic reference generator for wireless implantable system. The proposed generator is optimized to be tolerable for power supply variation in a small area with programmability to generate various reference voltages and currents. The measured power line sensitivity are 0.02 / 1.1%/V for voltage and current reference, respectively. This reference generator can operate for input voltage ranging from 1.5 V to 3.5 V and implemented in an area of 0.011 mm(2), which is the smallest monolithic reference generator in 0.25 μm technology to the best of our knowledge. The output can vary from 20 nA to 33 nA for current reference and from 0.71 V to 1.03 V for voltage reference.


[The regulation of stat3 signal transduction pathway to G1 to S phase of laryngocarcinoma cell].
To show that Stat3 played a key role in the G1 to S phase transition in laryngocarcinoma cells. Human laryngocarcinoma cell lines Hep-2 were transfected with Stat3 antisense oligonucleotide mediated by liposome, MTT assay was used to measure the proliferation, flow cytometry was applied to analyze the cell cycle, and the expressions of Stat3, phosphorylation specific Stat3 (tyrosine705), CyclinD1, Cyclin E, CDK2, CDK4, CDK6, p21 and p27 were detected by western blot. Hep-2 laryngocarcinoma cell lines expressed constitutively activated Stat3. Antisense oligonucleotide which directed blocked up the translation site resulted in growth inhibition, downregulation of Stat3, p-Stat3, Cyclins and CDKs, and upregulation of p21 and p27. Our findings suggested that Stat3 played an important role in the G1 to S phase transition in laryngocarcinoma cells, Stat3 orchestrated cell cycle by regulating the balance between CDK/Cyclin complex and CKI.


Knockout of SLy1 decreases double-negative thymocyte proliferation and protects mice from p53-induced tumor formation.
The lymphocyte-specific adapter protein SLy1 has previously been identified as indispensable for thymocyte development and T-cell proliferation and, recently, as a cause of X-linked combined immunodeficiency in humans that recapitulates many of the abnormalities reported in SLy1KO and SLy1d/d mice. As SLy1KO NK cells show increased levels of p53, we focused our research on the interdependency of SLy1 and p53 for thymocyte development. Using RT-PCR and immunoblot analysis, we observed increased levels of p53 as well as DNA damage response proteins in SLy1KO thymocytes. To test for rescue from SLy1-induced deficiencies in thymocyte development like reduced thymocyte numbers and reduced DN to DP progression, we generated a mouse model with T cell-specific p53-deficiency on an SLy1KO background and analyzed lymphocyte populations in these mice and respective controls. Astonishingly, SLy1KO -typical deficiencies were retained, showing that SLy1 is mechanistically independent of p53. Studies of apoptosis and proliferation in SLy1KO thymocytes revealed decreased proliferation in the DN3 subpopulation as a possible reason for the decreased thymocyte number. In mice with p53-deficient T cells, we observed tumor formation leading to reduced survival, preferentially in SLy1WT mice. Thus, we suggest that a SLy1-deficiency reduces proliferation, resulting in less hematologic tumors initiated by the p53-deficiency.


Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines.
Epidemiologic studies demonstrate significant environmental impact of maternal viral infection and obstetric complications on the risk of schizophrenia and indicate their detrimental influences on brain development in this disorder. Based on these findings, animal models for schizophrenia have been established using double stranded RNA, bacterial lipopolysaccharides, hippocampal lesion, or prenatal/perinatal ischemia. Key molecules regulating such immune/inflammatory reactions are cytokines, which are also involved in brain development, regulating dopaminergic and GABAergic differentiation, and synaptic maturation. Specific members of the cytokine family, such as interleukin-1, epidermal growth factor, and neuregulin-1, are induced after infection and brain injury; therefore, certain cytokines are postulated to have a central role in the neurodevelopmental defects of schizophrenia. Recently, to test this hypothesis, a variety of cytokines were administered to rodent pups. Cytokines administered in the periphery penetrated the immature blood-brain barrier and perturbed phenotypic neural development. Among the many cytokines examined, epidermal growth factor (or potentially other ErbB1 ligands) and interleukin-1 specifically induced the most severe and persistent behavioral and cognitive abnormalities, most of which were ameliorated by antipsychotics. These animal experiments illustrate that, during early development, these cytokine activities in the periphery perturbs normal brain development and impairs later psychobehavioral and/or cognitive traits. The neurodevelopmental and behavioral consequences of prenatal/perinatal cytokine activity are compared with those of other schizophrenia models and cytokine interactions with genes are also discussed in this review.


Trend 2010-2018 in the clinical use of GLP-1 receptor agonists for the treatment of type 2 diabetes in routine clinical practice: an observational study from Northeast Italy.
Several GLP-1 receptor agonists (GLP-1RA) have become available for the treatment of type 2 diabetes (T2D), and evidence on their beneficial effects has evolved. We evaluated how the clinical phenotype of patients initiating GLP-1RA changed from 2010 to 2018. This was a retrospective study conducted at six diabetes outpatient clinics in Northeast Italy. We collected data of T2D patients who initiated new GLP-1RA between 2010 and 2018. We recorded baseline characteristics, including demographics, anthropometrics, cardiovascular risk factors, glucose control, lipid profile, liver enzymes, renal function and concomitant medications. We recorded updated HbA1c and body weight at follow-up. There were 83,116 T2D patients from a general population of ~ 1,380,000 inhabitants. Among 6167 cases of GLP-1RA initiation, 5408 were analyzed after excluding intra-class switchers. Prescription of GLP-1RA increased exponentially, and the change in the type of GLP-1RA reflected waves of their entering the market. From 2010 to 2018, there were significant increases in baseline age, diabetes duration and prevalence of male sex, of cardiovascular disease and of insulin users. Blood pressure and cholesterol levels decreased concomitantly with increasing use of medications for the control of cardiovascular risk. Baseline average HbA1c (8.3% [67 mmol/mol]) and BMI (34 kg/m2) and their improvement after GLP-1RA initiation did not change over time. Despite the early positioning of GLP-1RA in T2D treatment algorithms, GLP-1RA have been prescribed in patients with progressively more advanced disease stage and especially in the presence of cardiovascular disease. Optimization of GLP-1RA use in routine clinical practice is still needed.


Xylo-oligosaccharides, fermentable sugars, and bioenergy production from sugarcane straw using steam explosion pretreatment at pilot-scale.
This study investigated the production of xylo-oligosaccharides (XOS) from sugarcane straw (SCS) using steam explosion (SE) pretreatment at pilot-scale, as well as co-production of fermentable sugars and lignin-rich residues for bioethanol and bioenergy, respectively. SE conditions 200 °C; 15 bar; 10 min led to 1) soluble XOS yields of up to 35 % (w/w) of initial xylan with ∼50 % of the recovered XOS corresponding to xylobiose and xylotriose, considered the most valuable sugars for prebiotic applications; 2) fermentable glucose yields from the enzymatic hydrolysis of SE-pretreated SCS of up to ∼78 %; 3) increase in the energy content of saccharified SCS residues (16 %) compared to the untreated material. From an integrated biorefinery perspective, it demonstrated the potential use of SCS for the production of value-added XOS ingredients as well as liquid and solid biofuel products.


The management of anorectal malformation with congenital vestibular fistula: a single-stage modified anterior sagittal anorectoplasty.
This study aimed to evaluate the mid-term outcomes of single-stage modified anterior sagittal anorectoplasty (ASARP) for anorectal malformation with vestibular fistula. Twenty-six patients with congenital imperforate anus and vestibular fistula underwent single-stage modified sphincter-saving ASARP between January 2008 and December 2012. The ages of the patients at the time of operation ranged from 1 month to 5.1 years. Standard ASARP procedure was modified to avoid the incision of the external sphincter complex. Instead a potential tunnel was created through the center of external sphincter complex under the endoscopic guidance. The patients were evaluated for fecal continence and complications. Modified ASARP was successfully performed in all patients. The mean operation time was 52.2 ± 3.5 min (range 47-61 min). The operative blood loss was minimal. There was no operative complication. Wound infection occurred in 3 patients (3/26, 11.5%). All patients were followed up for 4.2 ± 1.5 years (range 2-6 years). No patient developed fecal incontinence. Three patients (3/26, 11.5%) had soiling once or twice per week. Four patients (4/26, 15.4%) had constipation amenable to diet management. Mucosal prolapse occurred in 1 patient (1/26, 3.8%). There was no recurrence of fistula, anal stenosis or anterior displacement of the neorectum. Mid-term results show that single-stage modified ASARP is an effective and safe option for patients with anorectal malformation and congenital vestibular fistula.


B-mode ultrasound based CAD for liver cancers via multi-view privileged information learning.
B-mode ultrasound-based computer-aided diagnosis model can help sonologists improve the diagnostic performance for liver cancers, but it generally suffers from the bottleneck due to the limited structure and internal echogenicity information in B-mode ultrasound images. Contrast-enhanced ultrasound images provide additional diagnostic information on dynamic blood perfusion of liver lesions for B-mode ultrasound images with improved diagnostic accuracy. Since transfer learning has indicated its effectiveness in promoting the performance of target computer-aided diagnosis model by transferring knowledge from related imaging modalities, a multi-view privileged information learning framework is proposed to improve the diagnostic accuracy of the single-modal B-mode ultrasound-based diagnosis for liver cancers. This framework can make full use of the shared label information between the paired B-mode ultrasound images and contrast-enhanced ultrasound images to guide knowledge transfer It consists of a novel supervised dual-view deep Boltzmann machine and a new deep multi-view SVM algorithm. The former is developed to implement knowledge transfer from the multi-phase contrast-enhanced ultrasound images to the B-mode ultrasound-based diagnosis model via a feature-level learning using privileged information paradigm, which is totally different from the existing learning using privileged information paradigm that performs knowledge transfer in the classifier. The latter further fuses and enhances feature representation learned from three pre-trained supervised dual-view deep Boltzmann machine networks for the classification task. An experiment is conducted on a bimodal ultrasound liver cancer dataset. The experimental results show that the proposed framework outperforms all the compared algorithms with the best classification accuracy of 88.91 ± 1.52%, sensitivity of 88.31 ± 2.02%, and specificity of 89.50 ± 3.12%. It suggests the effectiveness of our proposed MPIL framework for the BUS-based CAD of liver cancers.


Sperm Genomic Integrity by TUNEL Varies throughout the Male Genital Tract.
We assessed sperm chromatin fragmentation at different levels of the male genital tract. Ejaculated specimens from consenting male partners were screened for sperm chromatin fragmentation by TUNEL (terminal deoxynucleotidyl deoxyuridine triphosphate nick end labeling). Men with intracytoplasmic sperm injection failure and high ejaculated sperm chromatin fragmentation underwent surgery to retrieve spermatozoa from different levels of the male genital tract, which were then reassessed for sperm chromatin fragmentation. Approximately 500 or more spermatozoa were assessed per patient with a 15% threshold. Intracytoplasmic sperm injection results of cycles using spermatozoa from different levels of the male genital tract were compared. Topographical assessment of the male genital tract showed a mean ± SD of 20.4% ± 10% sperm chromatin fragmentation in the vas deferens, 15.8% ± 8% in the epididymis and 11.4% ± 6% in the testis. All values were lower than in ejaculated controls (mean 32.9% ± 20%, p <0.05). A total of 25 couples who underwent intracytoplasmic sperm injection with surgically retrieved spermatozoa had lower sperm chromatin fragmentation (p <0.001), and higher implantation, clinical pregnancy and delivery rates (p <0.01). A total of 45 couples with a history of intracytoplasmic sperm injection failure with ejaculate performed elsewhere were treated solely with surgically retrieved spermatozoa at our center. Compared to historical cycles, surgically retrieved spermatozoa had a lower fertilization rate (65%, p <0.05) but enhanced rates of implantation (19.1%), clinical pregnancy (40.0%) and delivery (34.3%) (each p <0.01). To our knowledge we report for the first time that sperm chromatin fragmentation increases progressively from the testicle to the epididymis and the vas deferens, and is highest in the ejaculate. Men with high ejaculated sperm chromatin fragmentation can benefit from using surgically retrieved sperm for in vitro fertilization and/or intracytoplasmic sperm injection.


The impact of Ramadan fasting on the metabolic syndrome severity in relation to ethnicity and sex: Results of a systematic review and meta-analysis.
The primary goal of this meta-analysis was to examine the changes in various components of metabolic syndrome (MetS) in healthy adults who observed Ramadan fasting (RF) before Ramadan (T1) and at the end of RF (T2). A secondary goal was to assess the impact of RF on MetS severity in various ethnic and sex groups using the MetS z-score. Using PRISMA2020, seven databases were searched for relevant studies published between January 1950 and March 2022. Data extraction involved high-density lipoprotein cholesterol (HDL), triglycerides (TG), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) for T1 and T2, respectively. The MetS z-score was computed according to international diabetes federation criteria. At T1, the pooled estimates of HDL, TG, FBG, WC, SBP, DBP, and MAP were 1.20 [1.13; 1.27] mmol/L, 1.32 [1.23; 1.42] mmol/L, 4.98 [4.82; 5.15] mmol/L, 87.21 [84.21; 90.21] Cm, 114.22 [101.45; 126.99] mmHg, 76.80 [70.12; 83.47] mmHg, and 89.27 [80.56; 97.98] mmHg, respectively. At T2, the pooled estimates of HDL, TG, FBG, WC, SBP, DBP, and MAP were 1.24 [1.18; 1.31] mmol/L, 1.24 [1.14; 1.34] mmol/L, 4.77 [4.55; 4.99] mmol/L, 85.73 [82.83; 88.64] Cm, 109.48 [97.20; 121.75] mmHg, 74.43 [68.01; 80.85] mmHg, and 86.11 [77.74; 94.48] mmHg, respectively. The MetS z-score showed improvement at T2 for all ethnic groups and both sexes by -0.22 [-0.24; -0.01]. The current meta-analysis suggests that the RF positively impact the MetS components and the overall MetS z-score. ID CRD42022329297 OPEN SCIENCE FRAMEWORK IDENTIFIER: DOI 10.17605/OSF.IO/U9H7T.


D-dimer testing in the diagnosis of cerebral vein thrombosis: a systematic review and a meta-analysis of the literature.
Quantitative measurement of circulating D-dimer, a product of fibrin degradation, has been shown to be a very useful diagnostic tool in the management of patients with suspected deep vein thrombosis and/or pulmonary embolism. Whether D-dimer can play a similar role in the diagnostic approach to patients with suspected cerebral vein thrombosis (CVT) remains controversial. Studies evaluating the diagnostic accuracy of the D-dimer test in the diagnosis of CVT were systematically searched for in the MEDLINE and EMBASE databases (up to July 2011). Weighted mean sensitivity and specificity with 95% confidence intervals (CIs) were calculated with a bivariate random-effects regression approach. Fourteen studies, for a total of 1134 patients, were included. D-dimer accuracy was good, with a resulting weighted mean sensitivity of 93.9% (95% CI 87.5-97.1) and weighted mean specificity of 89.7% (95% CI 86.5-92.2), calculated with a bivariate approach. Potential risk factors for false-negative D-dimer results included isolated headache, longer duration of symptoms, and limited sinus involvement. Our findings suggest that D-dimer may be a useful diagnostic tool in the management of patients with suspected CVT. Future prospective studies are warranted to confirm our preliminary findings.


The role of parents in behavioral treatment for adolescent obesity: design and rationale for the TEENS+ randomized clinical trial.
There is an urgent need for innovative approaches to adolescent obesity treatment, particularly among individuals from racially and ethnically marginalized backgrounds, who face increased risk of obesity and its associated morbidity and mortality. There is a particular dearth of research on the long-term efficacy of adolescent obesity treatments. Further, research and clinical practice guidelines consistently recommend parents' inclusion in their adolescents' obesity treatment, yet the most effective strategy to engage parents in adolescent obesity treatment remains unclear. Towards that end, this investigation will conduct a fully-powered, randomized clinical trial to examine the efficacy of two distinct approaches to involving parents in their adolescents' obesity treatment. Participants will be 210 12-16 year old adolescents (body mass index [BMI]≥85th percentile) and parents (BMI≥25 kg/m2) with overweight or obesity. Dyads will be randomized to one of two 4-month treatments: 1) TEENS+Parents as Coaches (PAC), engaging parents as helpers in their child's weight management via parent skills training based on authoritative parenting, or 2) TEENS+Parent Weight Loss (PWL), engaging parents in their own behavioral weight management. All adolescents will participate in the TEENS+ protocol, which includes nutrition education with dietary goals, supervised physical activity, and behavioral support, and integrates motivational interviewing to enhance treatment engagement. Assessments of anthropometrics, dietary intake, physical activity, parenting and home environment variables will be completed at 0, 2, 4, 8, and 12 months with the primary endpoint at 12-month follow-up. Results of this investigation have the potential to significantly advance science in this area and ultimately inform clinical practice guidelines related to the role of parents in adolescent obesity treatment. Clinicaltrials.gov NCT03851796. Registered: February 22, 2019.


Relationship between age-associated endocrine deficiencies and muscle function in elderly women: a cross-sectional study.
Muscle receptors and selected anabolic effects have been identified for both insulin-like growth factor I (IGF-I) and 1,25-dihydroxyvitamin D (1,25(OH)2D3). The aim of the present study was to test the hypothesis that the decreasing concentrations of these endocrine factors might be involved in the decline in muscle function that characterizes normal human ageing. Cross-sectional study. A community-based sample of 245 healthy elderly women aged 70-90 years. Exclusion criteria were diseases or medications known to affect muscle function or the somatotrophic axis. Knee extension strength was evaluated using an isokinetic dynamometer. A standardized questionnaire was used to assess habitual physical activity. IGF-I and 1,25(OH)2D3 were measured by radioimmunoassay. Vitamin D binding protein (DBP) was measured by single radial immunodiffusion and the free 1,25(OH)2D3 concentration calculated as the molar ratio of total 1,25(OH)2D3 to DBP. The differences in isometric and isokinetic strength over the age range were equivalent to losses of 0.9-2.4% per year. However, no relationship was found between the somatotrophic axis or vitamin D status and knee extension strength, despite markedly decreasing concentrations of circulating IGF-I and free 1,25(OH)2D3 with age. Levels of circulating IGF-I and free 1,25(OH)2D3 appear not to be involved in the loss of muscle function that characterizes normal human ageing.


[Compounding techniques of bioactive ceramic and polymer biomaterials].
Some techniques of compounding bioactive ceramics and polymer biomaterials with mechanical and biological properties and the clinical applications of the composites produced are presented.


Diagnostic and therapeutic approaches for endometriosis: a patent landscape.
The aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field. Patent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords "Endometriosis OR Adenomyosis" AND "Diagnostic OR Therapeutics" were used along with wildcard search queries in the "Title", "Abstract" and "Descriptions" fields. A patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories. Efforts are being made to improve current diagnostic instruments. Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years.


Epigallocatechin-3-gallate Enhances Cognitive and Memory Performance and Protects Against Brain Injury in Methionine-induced Hyperhomocysteinemia Through Interdependent Molecular Pathways.
Brain injury and cognitive impairment are major health issues associated with neurodegenerative diseases in young and aged persons worldwide. Epigallocatechin-3-gallate (EGCG) was studied for its ability to protect against methionine (Met)-induced brain damage and cognitive dysfunction. Male mice were given Met-supplemented in drinking water to produce hyperhomocysteinemia (HHcy)-induced animals. EGCG was administered daily concurrently with Met by gavage. EGCG attenuated the rise in homocysteine levels in the plasma and the formation of amyloid-β and tau protein in the brain. Cognitive and memory impairment in HHcy-induced mice were significantly improved by EGCG administration. These results were associated with improvement in glutamate and gamma-aminobutyric acid levels in the brain. EGCG maintained the levels of glutathione and the activity of antioxidant enzymes in the brain. As a result of the reduction of oxidative stress, EGCG protected against DNA damage in Met-treated mice. Moreover, maintaining the redox balance significantly ameliorated neuroinflammation evidenced by the normalization of IL-1β, IL-6, tumor necrosis factor α, C-reactive protein, and IL-13 in the same animals. The decreases in both oxidative stress and inflammatory cytokines were significantly associated with upregulation of the antiapoptotic Bcl-2 protein and downregulation of the proapoptotic protein Bax, caspases 3 and 9, and p53 compared with Met-treated animals, indicating a diminution of neuronal apoptosis. These effects reflect and explain the improvement in histopathological alterations in the hippocampus of Met-treated mice. In conclusion, the beneficial effects of EGCG may be due to interconnecting pathways, including modulation of redox balance, amelioration of inflammation, and regulation of antiapoptotic proteins.


Lessons from America? Commercialization and growth of private medicine in Britain.
This article examines the transition of the private medical sector in Britain from a mere appendage to the National Health Service to a significant business sector involving multinational enterprise. The author argues that private medicine continues to be in a state of flux because its degree of independence is limited by its links to the dominant public sector, particularly with regard to staffing, and is still vulnerable to attacks from the opposition parties. Private medicine, despite rapid growth in the late 1970s, is beset by mounting costs and intense competition.


Structure and immunological activity of an arabinan-rich acidic polysaccharide from Atractylodes lancea (Thunb.) DC.
An arabinan-rich acidic polysaccharide, named ALP4-2 ([α]20 D = +197.8 (c 1.0 mg/mL, H2O); and Mw = 5.59 × 103 g/mol), was obtained from Atractylodes lancea (Thunb.) DC. ALP4-2 is mainly comprised of Ara along with a small amount of GalA, Gal, Rha, Glc and Xyl. The structure was decorated by glycosidic linkages of α-Araf-(1→, →3)-α-Araf-(1→, →5)-α-Araf-(1→, →3,5)-α-Araf-(1→, →2,4)-α-Rhap-(1→, α-GalAp-(1→, →4)-α-GalAp-6-OMe-(1→, →4)-α-GalAp-6-OMe and β-Galp-(1→ with a ratio of 6:1:7:5:5:1:7:1:4. The structure, configuration and microstructure of ALP4-2 was proposed by comprehensive considerations of results from SEC-MALLS-RID, SEC-HRMS, GC-MS, and 1D/2D NMR spectroscopy. Except for a high methyl ester in full pectin regions, an abundant arabinan moiety is observed in ALP4-2 with highly complex and branched characteristics. The immunoactivity displayed that ALP4-2 can significantly promote phagocytosis of macrophage without cytotoxicity, and stimulate nitric oxide and cytokines (TNF-α, IL-6 and IL-10) release on RAW 264.7.


Progress and remaining challenges for cancer control in the Gulf Cooperation Council.
Cancer is a growing global health-care problem, especially in under-resourced countries. Cancer prevalence in Gulf Cooperation Council (GCC) countries is projected to increase, potentially leading to a major burden on the economy. Policy makers in GCC countries have invested in the development of National Cancer Control Strategies to address the current and future burden of cancer through different initiatives and policies for prevention, early detection, and management of cancer. These strategies include capacity building, health education, and global partnerships to strengthen health-care systems. The aim of this Review is to highlight the status of cancer control programmes in GCC countries, describe what has been achieved to date, and identify the gaps, with recommendations on how to lower the burden of cancer in the Gulf region in the future. TRANSLATION: For the Arabic translation of the abstract see Supplementary Materials section.


Studies on the mechanism of the NADPH-catalyzed peroxidation of endogenous microsomal lipid.
The importance of metal chelation in the mechanism of microsomal lipid peroxidation has been studied using both phosphate- and sulfhydryl-containing compounds. The optimal concentration for maximum stimulation by each of these compounds has been determined, and the decrease in stimulation observe at concentrations above the maxima has been related to the ability of these compounds to form stable chelation complexes with non-heme iron. Of the compounds tested, only ADP and ATP facilitated the cooperative binding of NADPH to the membrane and thus suggested the possibility of three binding sites for NADPH. Neither of the other two phosphate-chelating agents (Pi or PPi) and neither of the two thiols (cysteine or dithiothreitol)facilitated cooperative binding of NADPH. These data suggested that the adenine ring of ADP or ATP is directly involved in the cooperativity of NADPH binding. They also emphasized that the binding of the chelation complex to the protein is an important parameter in the mechanism of the NADPH-catalyzed peroxidation of endogenous microsomal lipids. Furthermore, stimulation of the rat of lipid peroxidation by sulhydryl-containing compounds, by freezing thawing the microsomal protein, and by treatment of the protein with detergent may be due to a decrease in this cooperative binding effect. Since cysteine and deoxycholate as well as freezing and thawing alter membrane structure, the stimulation of lipid peroxidation seems to involve some alteration to the structure of the microsomal membrane prior to the onset of enzymatic lipid peroxidation.


Psychosocial factors associated with symptoms of depression, anxiety and stress among single mothers with young children: A population-based study.
Abundant evidence highlights single parenthood as a common risk factor for depression, anxiety and stress but few studies have comprehensively examined psychosocial factors (adversities), particularly during early parenting. We investigated symptom prevalence and potential risk factors among mothers with very young children. Data stem from the 2015 National Psychosocial Burdens Prevalence Study (KiD 0-3). Mothers with children up to 3 years of age (n = 6925) were recruited from random probability-sampled paediatric clinics (n = 271) across Germany and reported on depression or anxiety, general and parenting stress using the Patient Health Questionnaire (PHQ-4), Perceived Stress Scale (PSS-4) and Parenting Stress Index (PSI). Multivariable logistic regression models determined risk factors and quantified potential mediation of psychosocial factors for all 3 outcomes. Approximately 30% of single mothers (n = 517) reported depressive or anxiety symptoms and 37% general stress, twice as high compared to partnered mothers (n = 6408; p < 0.0001). Parenting stress was also elevated (p < 0.0001). Adjusted regression models confirm that single mothers are twice as likely to report symptoms of depression or anxiety (OR 1.9, CI95% 1.4-2.5). Risk factors for stress correspond to those for depression and anxiety. Inadequate social support and history of partner or childhood maltreatment were also consistent risk factors across all outcomes. The study design and self-reported symptoms are limitations to consider. Single mothers with young children are more predisposed to mental health disorders than partnered mothers, especially when facing financial, social or distal adversities. Appropriate social support programs and screening measures are necessary to reduce further disparities.


3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis.
Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide. Cetuximab, in combination with chemotherapy, is effective for treating patients with wild-type KRAS/BRAF metastatic CRC (mCRC). However, intrinsic or acquired drug resistance often limits the use of cetuximab. In this study, we investigated the potential of co-treatment with 3-Bromopyruvate (3-BP) and cetuximab to overcome cetuximab resistance in CRC, both in vitro and in vivo. Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines with intrinsic cetuximab resistance (DLD-1 (KRASG13D/-) and HT29 (BRAFV600E)) and in a cetuximab-resistant cell line derived from Caco-2 with acquired resistance (Caco-2-CR). Further analysis revealed that co-treatment induced ferroptosis, autophagy, and apoptosis. Mechanistically, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1 (KRASG13D/-), HT29 (BRAFV600E), and Caco-2-CR cells. In conclusion, our findings suggest that co-treatment with 3-BP and cetuximab could be a promising strategy to overcome cetuximab resistance in human CRC.


The small GTPase Rap1 is an immediate downstream target for Hoxb4 transcriptional regulation.
The Hox genes are a family of homeodomain-containing transcription factors which determine anteroposterior identity early on in development. Although a lot is now known about their regulation and function, very little is known of their effector (downstream target) genes. Here we show that the small GTPase Rap1 is a direct, negatively regulated target of Hoxb4 and is excluded from Hoxb4 expressing cells.