Best practice guide for the treatment of nightmare disorder in adults.
Prazosin is recommended for treatment of Posttraumatic Stress Disorder (PTSD)-associated nightmares. Level A. Image Rehearsal Therapy (IRT) is recommended for treatment of nightmare disorder. Level A. Systematic Desensitization and Progressive Deep Muscle Relaxation training are suggested for treatment of idiopathic nightmares. Level B. Venlafaxine is not suggested for treatment of PTSD-associated nightmares. Level B. Clonidine may be considered for treatment of PTSD-associated nightmares. Level C. The following medications may be considered for treatment of PTSD-associated nightmares, but the data are low grade and sparse: trazodone, atypical antipsychotic medications, topiramate, low dose cortisol, fluvoxamine, triazolam and nitrazepam, phenelzine, gabapentin, cyproheptadine, and tricyclic antidepressants. Nefazodone is not recommended as first line therapy for nightmare disorder because of the increased risk of hepatotoxicity. Level C. The following behavioral therapies may be considered for treatment of PTSD-associated nightmares based on low-grade evidence: Exposure, Relaxation, and Rescripting Therapy (ERRT); Sleep Dynamic Therapy; Hypnosis; Eye-Movement Desensitization and Reprocessing (EMDR); and the Testimony Method. Level C. The following behavioral therapies may be considered for treatment of nightmare disorder based on low-grade evidence: Lucid Dreaming Therapy and Self-Exposure Therapy. Level C No recommendation is made regarding clonazepam and individual psychotherapy because of sparse data.


Identifying Variability in Patient Characteristics and Prevalence of Emergency Department Utilization for Mental Health Diagnoses in Rural and Urban Communities.
In order to redirect at-risk patients to more appropriate, cost-effective behavioral health care, research must identify the prevalence, and common characteristics, of patients presenting to the emergency department (ED) for mental disorders. Are large, small, and/or isolated rural patients presenting to the ED for mental disorders in greater proportion than urban ED patients? Analyses included data from the Health Care Cost and Utilization Project State Emergency Department Databases (2013) provided by 7 states, covering all Census regions. Variables included patient demographics, ZIP code, and primary and secondary ED diagnoses. ZIP codes were linked to the Rural-Urban Commuting Areas, aggregating into 4 categories. Prevalence rates were compared within and between groups (P < .05). Nearly 1 in 20 ED visits carried a primary/secondary diagnosis of mental disorder. Large, small, and isolated rural patients were not more likely than urban patients to present to the ED for mental disorders. Large, small, and isolated rural residents diagnosed with a primary/secondary mental disorder in the ED were more likely than urban to be female, 65 years of age or older, covered by Medicaid or Medicare, and dual eligible. The top 3 diagnoses for mental disorders in the ED were anxiety-state, unspecified; depressive disorder; and suicidal ideation. EDs treating large, small, or isolated rural patients with mental disorders are more likely to treat populations identified in the literature at greater risk of preventable visits, readmitting, and more costly care. Recommendations are made for policy, community interventions, workforce, and training.


Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9.
Halofuginone (HF) is extracted from Dichroa febrifuga, a plant used in traditional medicine. We report that the HF extract inhibits the growth of breast cancer cells and induces the generation of reactive oxygen species (ROS) and apoptosis, an important feature of potential anticancer agents. In addition, HF significantly reduces the migration and invasion of MCF-7 and MDA-MB-231 human breast cancer cells after 12-O-tetraecanoylphorbol-13-acetate (TPA) stimulation. As matrix metalloproteinase-9 plays a critical role in tumor metastasis, we analyzed its expression with the HF extract treatment. Western blot analysis and gelatin zymography showed that HF suppresses MMP-9 expression and activity concentration-dependently. HF also decreases the nuclear protein levels of nuclear factor kappa B (NF-κB) and c-fos (AP-1), critical transcription factors regulating MMP-9 expression through binding the MMP-9 promoter region. Luciferase assays showed that HF decreases TPA-induced MMP-9 promoter binding activities of NF-κB and AP-1. Taken together, these are the first results indicating that halofuginone may represent a promising new agent for breast cancer chemotherapy.


Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system.
Three of at least 8 Fanconi anemia (FA) genes have been cloned (FANCA, FANCC, FANCG), but their functions remain unknown. Using the yeast 2-hybrid system and full-length cDNA, the authors found a strong interaction between FANCA and FANCG proteins. They also obtained evidence for a weak interaction between FANCA and FANCC. Neither FANCA nor FANCC was found to interact with itself. These results support the notion of a functional association between the FA gene products. (Blood. 2000;95:719-720)


A new scheme for electronegativity equalization as a source of electronic descriptors: application to chemical reactivity.
Recently, we have proposed a new unconventional scheme of electronegativity equalization. We assume that atomic electronegativities are equalized in a molecule in the same manner as electrical potentials in the nodes of a closed electrical network, with the molecule being represented by a molecular graph (MG). Computational procedure includes several operations over the matrices associated with MG. The only parameter used is the atomic electronegativity (EN). The method is very fast and easy-to-implement. With the help of the method one can generate a family of electronic descriptors (equalized or "effective" ENs and atomic charges) which are applicable to the treatment of some types of chemical reactivity. Quite good correlations of the descriptors obtained are observed for such thermodynamic and kinetic data as proton affinity and Taft's inductive sigma* constants. The EN equalization scheme suggested can be used as an independent tool for molecular electrostatics modeling, or can be implemented into an integrated QSAR software.


TESTIS SPARING SURGERY FOR ADULT MATURE TERATOMA OF THE TESTIS; REPORT OF A CASE.
A 25-year-old man presented complaining of a painful, left scrotal swelling. He first noticed a mass in his left scrotum during childhood, but, in the absence of clinical symptoms, did not seek medical attention. We detected a left testicular tumor which was elastic, firm and smooth. Serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) were all within normal range. Magnetic resonance imaging (MRI) and ultrasound revealed a solid tumor with cysts accompanied by intracystic hemorrhage and calcified walls. From the above findings, the tumor was suspected to be benign and, we therefore planned testis-sparing surgery. We performed tumor enucleation under cold ischemia. Since an intraoperative frozen section revealed the tumor to be benign, we preserved the remaining testis as planned. The final pathologic diagnosis was a mature teratoma without a malignant germ cell component. Evidence of recurrence has not been observed five years after the operation. In conclusion, when a mature teratoma that has been present since prepuberty is suspected in an adult, testis-sparing surgery should be considered.


Efficacy of Non-ablative Laser Therapy for Lichen Sclerosus: A Randomized Controlled Trial.
The aim of this randomized controlled trial was to evaluate the safety and efficacy of neodymium: yttrium aluminum garnet laser treatment of lichen sclerosus (LS) by comparing it with topical corticosteroid treatment. A total of 40 female patients with vulvar LS were randomized 1:1 into a study (laser) group and a control (topical corticosteroids) group. The laser group received three laser treatments. Blinded evaluators evaluated biopsies and graded improvement on clinical photographs at baseline and at 3 months. Patients graded the intensity of symptoms on a 0 to 10 visual analogue scale at baseline and 1-, 3-, and 6-month follow-up. Patients also rated the tolerability of laser treatments, and side effects were monitored. (Canadian Task Force classification I) RESULTS: Laser treatment discomfort was on average 1.5 of 10 on the visual analogue scale. At 1- and 3-month follow-up, patients in the laser group had significantly greater improvement in LS symptoms (burning, itching, pain, and dyspareunia), better patient satisfaction, and greater reduction of sclerosis than patients in the topical corticosteroid group. At 6-month follow-up, the improvement of symptoms in the laser group was still significant. The correct order of photographs (before and after treatment) was assigned significantly more often in the laser-treated patients compared with the control group. Laser therapy for LS caused minimal patient discomfort during the treatment, with no adverse effects, and demonstrated better efficacy than in the control group, with significant improvement lasting up to 6 months. Laser therapy is a promising option for patients not responding to topical corticosteroid therapy or patients wishing to reduce long-term corticosteroid maintenance use.


The direct approach to gravitation and electrostatics method for periodic systems.
The direct approach to gravitation and electrostatics (DAGE) algorithm is an accurate, efficient, and flexible method for calculating electrostatic potentials. In this paper, we show that the algorithm can be easily extended to consider systems with many different kinds of periodicities, such as crystal lattices, surfaces, or wires. The accuracy and performance are nearly the same for periodic and aperiodic systems. The electrostatic potential for semiperiodic systems, namely defects in crystal lattices, can be obtained by combining periodic and aperiodic calculations. The method has been applied to an ionic model system mimicking NaCl, and to a corresponding covalent model system.


Mesenchymal Stem Cells as a Biological Drug for Heart Disease: Where Are We With Cardiac Cell-Based Therapy?
Cell-based treatment represents a new generation in the evolution of biological therapeutics. A prototypic cell-based therapy, the mesenchymal stem cell, has successfully entered phase III pivotal trials for heart failure, signifying adequate enabling safety and efficacy data from phase I and II trials. Successful phase III trials can lead to approval of a new biological therapy for regenerative medicine.


Why ethnic minority groups are under-represented in clinical trials: a review of the literature.
Randomised controlled trials (RCTs) are considered to be the gold standard in evaluating medical interventions; however, people from ethnic minorities are frequently under-represented in such studies. The present paper addresses a previously neglected debate about the tensions which inform clinical trial participation amongst people from ethnic minorities, in particular, South Asians, the largest ethnic minority group in the UK. In a narrative review of the available literature, based mainly on US studies, the present authors aim to make sense of the issues around under-representation by providing a theoretical reconciliation. In addition, they identify a number of potential barriers to ethnic minority participation in clinical trials. In so doing, the authors recognise that the recent history of eugenic racism, and more general views on clinical trials as a form of experimentation, means that clinical trial participation among people from ethnic minorities becomes more problematic. Lack of participation and the importance of representational sampling are also considered, and the authors argue that health professionals need to be better informed about the issues. The paper concludes by offering a number of strategies for improving ethnic minority accrual rates in clinical trials, together with priorities for future research.


Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation.
The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional endocytic receptor that is expressed abundantly in neurons of the CNS. Both LRP and several of its ligands, including tissue plasminogen activator (tPA), apolipoprotein E/lipoproteins, alpha(2)-macroglobulin, and the beta-amyloid precursor protein, have been implicated in various neuronal functions and in the pathogenesis of Alzheimer's disease. It has been reported that induction of tPA expression may contribute to activity-dependent synaptic plasticity in the hippocampus and cerebellum. In addition, long-term potentiation (LTP) is significantly decreased in mice lacking tPA. Here we demonstrate that tPA receptor LRP is abundantly expressed in hippocampal neurons and participates in hippocampal LTP. Perfusion of hippocampal slices with receptor-associated protein (RAP), an antagonist for ligand interactions with LRP, significantly reduced late-phase LTP (L-LTP). In addition, RAP also blocked the enhancing effect of synaptic potentiation by exogenous tPA in hippocampal slices prepared from tPA knock-out mice. Metabolic labeling and ligand binding analyses showed that both tPA and LRP are synthesized by hippocampal neurons and that LRP is the major cell surface receptor that binds tPA. Finally, we found that tPA binding to LRP in hippocampal neurons enhances the activity of cyclic AMP-dependent protein kinase, a key molecule that is known to be involved in L-LTP. Taken together, our results demonstrate that interactions between tPA and cell surface LRP are important for hippocampal L-LTP.


Minor histocompatibility antigens.
The existence of transplantation antigens, in addition to those encoded by genes in the MHC, has been known for over half a century. The molecular identification of these additional minor histocompatibility (H) antigens lagged behind that of their MHC counterparts, largely because minor H antigens are recognised by T cells and not by antibodies. In the past year, however, new minor H antigens have been identified at both the genetic and protein level and include Uty, a second novel gene encoding a male-specific epitope in mice, a novel autosomal gene encoding each of the H-13 alleles of mice, and a second male-specific epitope encoded by the SMCY gene.


Lipid peroxidation induced by the Cu,Zn-superoxide dismutase and hydrogen peroxide system.
Cu,Zn-superoxide dismutase (SOD) can catalyze hydroxyl radical generation using H2O2 as a substrate. Lipid peroxidation induced by the Cu,Zn-SOD and H2O2 system was investigated. When linoleic acids micelles or phosphatidylcholine liposomes were incubated with Cu,Zn-SOD and H2O2, lipid peroxidation was gradually increased in a time-dependent manner. The extent of lipid peroxidation was proportional to Cu,Zn-SOD and H2O2 concentrations. Hydroxyl radical scavengers and copper chelator inhibited lipid peroxidation induced by the Cu,Zn-SOD and H2O2 system. These results suggest that lipid peroxidation is mediated by the Cu,Zn-SOD and H2O2 system via the generation of hydroxyl radicals by a combination of the peroxidative reaction of Cu,Zn-SOD and the Fenton-like reaction of free copper released from oxidatively damaged SOD.


Age-related changes in cortical blood flow activation during perception and memory.
Although many cognitive functions are affected by age, some are relatively maintained. There also are numerous age-related changes in brain structure, but not much is known about how these changes impact upon the alterations seen in cognition. In order to understand the basis for the reductions and sparings of cognitive function in the aged, experiments were carried out to compare regional cerebral blood flow (rCBF) and performance in young and old subjects on visual perceptual and memory tasks. In the first experiment, which examined the perception of faces and spatial locations, old subjects were as accurate as young subjects, and both groups had rCBF activation in fusiform gyrus during face matching and in superior parietal cortex during location matching. However, old subjects had less activation of prestriate cortex and more activation of frontal and lateral temporal cortex than did young subjects. The second experiment tested recognition memory for faces, a task on which old subjects were impaired. Young subjects had rCBF activation in left prefrontal and inferior temporal cortex and in right hippocampus during encoding of the faces, and in right prefrontal and parietal cortex during recognition. Old subjects showed no significant activation of the areas involved in encoding, but did have increased rCBF in right prefrontal cortex during recognition. These results suggest that the aging brain can demonstrate alterations of the functional systems involved in some cognitive processes, such as perception, that may serve as a compensatory mechanism to maintain performance. Failure to show such compensation, coupled with dysfunction of the areas primarily involved in processing may lead to more marked deficits in performance.


Polyoxometalate-Surfactant Hybrids Directed Assembly of Ni3S2 into Hollow Microsphere as Pt-Comparable Electrocatalyst for Hydrogen Evolution Reaction in Alkaline Medium.
A large surface area of catalytic sites and low electric resistance are desirable properties for electrocatalysts that lower the overpotential required for electrochemical reactions, such as the hydrogen evolution reaction (HER), in this study. In the presence of polyoxometalate (POM) and triblock copolymer pluronic (P123) as a hybrid soft template, the hydrothermal sulfurization of nickel foam leads to the formation of a hollow microsphere, assembled from the Ni3S2 motif. Sonication for preparing POM+P123 hybrids, while adjusting the POM content, is an effective strategy for synthesizing a Pt-like electrocatalyst with excellent hydrogen evolution efficiency. The reason is that both sonication and optimal POM content can simultaneously enhance the electroactive surface area and electron transfer of the Ni3S2 electrocatalyst. Adopting the optimal conditions, the three-dimensional porous network, composed of Ni3S2 hollow microspheres on the nickel foam, shows that the HER in an alkaline medium requires only 77 mV overpotential for a current density of 10 mA cm-2, with a robust long-term stability during a 25 h test. The performance at a large current density outperforms the current benchmark electrocatalyst (Pt) for HER.


Innovating a Nonconventional Yeast Platform for Producing Shikimate as the Building Block of High-Value Aromatics.
The shikimate pathway serves an essential role in many organisms. Not only are the three aromatic amino acids synthesized through this pathway, but many secondary metabolites also derive from it. Decades of effort have been invested into engineering Saccharomyces cerevisiae to produce shikimate and its derivatives. In addition to the ability to express cytochrome P450, S. cerevisiae is generally recognized as safe for producing compounds with nutraceutical and pharmaceutical applications. However, the intrinsically complicated regulations involved in central metabolism and the low precursor availability in S. cerevisiae has limited production levels. Here we report the development of a new platform based on Scheffersomyces stipitis, whose superior xylose utilization efficiency makes it particularly suited to produce the shikimate group of compounds. Shikimate was produced at 3.11 g/L, representing the highest level among shikimate pathway products in yeasts. Our work represents a new exploration toward expanding the current collection of microbial factories.


Clues to immune tolerance: the monogenic autoimmune syndromes.
Autoimmune disease affects a significant proportion of the population. The etiology of most autoimmune diseases is largely unknown, but it is thought to be multifactorial with both environmental and genetic influences. Rare monogenic autoimmune diseases, however, offer an invaluable window into potential disease mechanisms. In this review, we will discuss the autoimmune polyglandular syndrome (APS1), the immunedysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), and autoimmune lymphoproliferative syndrome (ALPS). Significantly, the information gained from the study of these diseases has provided new insights into more common autoimmune disease and have yielded new diagnostics and therapeutic opportunities.


Molecular characterization of Dipetalonema yatesi from the black-faced spider monkey (Ateles chamek) with phylogenetic inference of relationships among Dipetalonema of Neotropical primates.
Species of the genus Dipetalonema are parasitic nematodes of the family Onchocercidae (Nematoda; Filarioidea) which infect the peritoneal cavity of Neotropical primates. Of these, six species have been taxonomically described, two of these have been reported infecting the black-faced spider monkey (Ateles chamek): Dipetalonema gracile and Dipetalonema yatesi. Description of Dipetalonema species have been based on morphological characteristics, and their phylogenetic relationships remain unresolved. A few molecular studies have been carried out in Dipetalonema spp. infecting Neotropical primates. Seven filarioid nematodes (6 females and one male) recovered from one A. chamek in the Peruvian Amazon rainforest were morphologically identified as D. yatesi and molecularly characterized. A multi-locus genetic analysis of nuclear ribosomal region (18S) and mitochondrial (cox1, 12S, and nad5) gene sequences supported D. yatesi as a distinct lineage and yielded a highly resolved phylogenetic lineage tree for this filarioid genus of Neotropical primates. Our results highlighted that Dipetalonema species are divided in two well-supported clades, one containing D. yatesi and D. caudispina, and the second containing D. robini, D. gracile, and D. graciliformis. Due to sequence ambiguities from GenBank entries, relationships among isolates of D. gracile and D. graciliformis cannot be fully resolved, which requires further investigation. However, this suggests that these could represent a species complex. Our study confirms that D. yatesi is a valid species and constitutes the first molecular phylogenetic analysis of this parasite in black-faced spider monkeys.


Mechanical interdependence of version and vergence eye movements.
In this paper, the authors investigate whether the idea of independent control of version and vergence eye movements is compatible with the mechanics of the eye plant. By computing the change in the axes of action of the eye muscles as a function of ocular vergence, they prove that, regardless of the muscle pulley locations, the required muscle activity for vertical version depends on the initial vergence angle. The binocular extension of Listing's law ('L2') describes how the torsional orientation of the eye depends on both gaze direction and ocular convergence. The authors show that for each vergence angle there is a range of possible muscle pulley locations that would cause independent control of version and vergence to result in L2. They also show that this mechanical explanation of L2 requires that the muscle pulleys move as a function of vergence.


Effectiveness of Telementoring in Improving Provider Knowledge, Attitudes, and Perceived Competence in Managing Chronic Pain: A Mixed Methods Study.
Telementoring is an evidence-based approach to meet the educational needs of primary care providers (PCPs) and to improve the quality of chronic pain care. This mixed methods study evaluated the effectiveness of pain management telementoring in improving provider knowledge, attitudes, and perceived competence. The study was conducted at Madigan Army Medical Center. Using a non-randomized quasi-experimental approach, 25 providers were assigned to intervention arm and control arm (14 intervention and 13 control). Providers in the intervention group attended telementoring sessions. Videoconference technology was used to deliver weekly 90-minute TelePain sessions to the PCPs in the intervention group. The first 25-30 minutes of each session consisted of a didactic presentation led by a panel of interdisciplinary pain management clinicians. During the remaining 60 minutes, all PCPs in the intervention group presented clinical histories and asked specific management questions regarding patients of their choosing. An interdisciplinary panel of pain management clinicians provided telementoring consultations. The panel included experts from pain medicine, primary care, psychology or psychiatry, chiropractic, clinical pharmacy, and nursing. Changes in provider knowledge, attitudes, and perceived competence were evaluated using the Knowledge and Attitudes Survey Regarding Pain, KnowPain-12, and the Perceived Competence Scale (n = 23; 12 intervention and 11 control). Qualitative interviews were conducted among a subset of providers (n = 12; 8 intervention and 4 control), and provider narratives were analyzed using content analysis. Increased provider knowledge (Z = 2.0, P = .046 [KnowPain-12]) and perceived competence (Z = 2.1, P = .033) were observed among intervention group providers. Provider narratives supported more implementation of non-pharmacological pain management strategies, use of strategies to engage patients in reducing reliance on opioids, and perception of TelePain as a helpful resource especially in the context of inadequate preparation in chronic pain management during professional training. Telementoring may hold significant potential to support providers in their efforts to decrease use of prescription opioids. Overall, this study provides further support for the value of telementoring in improving comprehensive chronic pain management in military settings.


Significance of Gram's stain smear, potassium hydroxide mount, culture, and microscopic pathology in the diagnosis of acrodermatitis continua of Hallopeau.
A 21-year-old housewife presented to the authors' clinic in 2009 with recurrent papulovesicular and pustular eruptions on the index an ring fingers of the left hand accompanied by throbbing pain that had been active for the past 10 years. The condition did not respond to topical and/or systemic treatment. There was neither a personal/family history of psoriasis nor any other systemic disease. The sk surface of the patient's left hand was marked by the presence of multiple pustules located over an erythematous background, affecting th ring and adjoining middle fingers, with crusting prominent in places along the tips (Figure 1). Gram-stained smears prepared from th purulent specimen revealed Gram-positive cocci in clusters. Potassium hydroxide (KOH) examination of the pustules did not show a fungal elements. In vitro culture of the same specimen yielded growth of Staphylococcus aureus, which was found to be sensitive to almo all conventional antibiotics on aerobic culture. Sections prepared from the skin of the tip of the patient's finger showed marked epithelial hyperplasia with uniform elongation of rete ridges and supra-papillary thinning of the epidermis. There was hyperkeratosis with foci of mounds of parakeratosis. Spongiosis with neutrophilic infiltration and microabscess formation were prominent. The dermis showed perivascular lymphohistiocytic infiltrate (Figure 2A and 2B). No organism was identified on special stains. Results from hemography and liver and renal function tests were within normal limits. The diagnosis of acrodermatitis continua of Hallopeau (ACH) was made, in keeping with the findings. The patient received ceftriaxone 1.0 g and tazobactam 125 mg by slow intravenous infusion for 3 consecutive days, following which there was complete regression of the lesions. After cessation of therapy, there was complete recurrence.


[Effects of L-carnitine and bisoprolol on endoplasmic reticulum stress-mediated myocardial injury after cardiopulmonary resuscitation in rats].
To explore the effects of L-carnitine and bisoprolol on endoplasmic reticulum stress-mediated myocardial injury after cardiopulmonary resuscitation in rats. A total of 75 Sprague-Dawley rats were randomly divided into 5 groups of sham operation (sham); cardiopulmonary resuscitation (CR), L-carnitine (L), bisoprolol treatment (B) and L-carnitine and bisoprolol treatment (LB). Myocardial pathological changes were detected by hematoxylin and eosin, myocardial apoptosis by terminal deoxynucleotidyl transferase mediated dUTP nick and the expressions of key factors in endoplasmic reticulum (ER) by Western blot. Compared with sham group, apoptosis and pathological lesions significantly increased in other groups (P < 0.05). And the levels of GRP78, CHOP and Caspase-12 were significantly higher (P < 0.05). The expression of ER factor protein and the degrees of myocardial injury in LB and B groups decreased compared with CR group. And LB group was the most obvious. Combined use of levocarnitine and bisoprolol exerts protective effects on cardiopulmonary resuscitation in rats. And the mechanism may be related to an inhibition of ER stress.


Lung Diffusion Capacity can Predict Maximal Exercise in Apparently Healthy Heavy Smokers.
Chronic exposure to tobacco smoking may damage lung and heart function. The aim of this study was to assess maximal exercise capacity and its relationship with lung function in apparently healthy smokers. We recruited 15 heavy smokers (age 47 years ± 7, BMI 25 kg/m(2) ± 3, pack/years 32 ± 9) without any cardiovascular or pulmonary signs and symptoms. Fifteen healthy non smoking subjects were enrolled as a control group. All subjects underwent pulmonary function tests, electrocardiograms at rest and graded cycle exercise tests. In smokers and controls, resting lung and cardiac function parameters were in the normal range, apart from diffusing lung capacity (TLCO) values which were significantly lower in smokers (p < 0.05). As compared to controls, smokers presented lower maximal exercise capacity with lower values at peak of exercise of oxygen uptake (peak VO2), workload, oxygen uptake/watt ratio and oxygen pulse (p < 0.05) and higher dyspnoea perception (p < 0.05). Moreover, peak VO2, maximal workload and oxygen pulse at peak exercise were related to and predicted by TLCO (p < 0. 05). Our study confirms that maximal exercise capacity is reduced in apparently healthy heavy smokers, and shows that TLCO explains some of the variance in maximal exercise. Key pointsChronic exposure to tobacco smoking may damage lung and heart function.Smokers present lower diffusion capacity and maximal exercise capacity.In smokers maximal exercise capacity can be predicted by resting diffusion lung capacity.


Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of Swine Mandibular Critical Size Defects: In Vivo Study.
Reconstruction of jaw bone defects present a significant problem because of specific aesthetic and functional requirements. Although widely used, the transplantation of standard autograft and allograft materials is still associated with significant constraints. Composite scaffolds, combining advantages of biodegradable polymers with bioceramics, have potential to overcome limitations of standard grafts. Polyethyleneimine could be an interesting novel biocompatible polymer for scaffold construction due to its biocompatibility and chemical structure. To date, there have been no in vivo studies assessing biological properties of hydroxyapatite bioceramics scaffold modified with polyethyleneimine. The aim of this study was to evaluate in vivo effects of composite scaffolds of hydroxyapatite ceramics and poly(lactide-co-glycolide) and novel polyethyleneimine on bone repair in swine's mandibular defects, and to compare them to conventional bone allograft (BioOss). Scaffolds were prepared using the method of polymer foam template in three steps. Pigs, 3 months old, were used and defects were made in the canine, premolar, and molar area of their mandibles. Four months following the surgical procedure, the bone was analyzed using radiological, histological, and gene expression techniques. Hydroxyapatite ceramics/polyethyleneimine composite scaffold demonstrated improved biological behavior compared to conventional allograft in treatment of swine's mandibular defects, in terms of bone density and bone tissue histological characteristics.


U.S. immigration and ethnicity in the 21st century.
The authors attempt to predict future U.S. immigration trends in light of changing policies. "Changes in policy and the presence of illegal entrants complicates measuring and projecting immigration flows. Acknowledging the risks, this article sketches the possible long-term impact of the immigration trends we observe today, if they were to continue for the next 50 years. This study uses a modified cohort-component approach for population projections by race/ethnicity and immigrant generation."


[The intensive therapy of brain edema by using clofelin and a hypertonic solution of sodium chloride in neurosurgical patients].
Efficacy was studied of combined use of clophelinum and hypertonic solution of sodium chloride during intensive therapy of brain edema in 32 patients with brain tumors. The above preparations provided efficient dehydration therapy that entailed regression of prior neurological deficit in the postoperative period, with blood plasma osmolarity values remaining in the normal range.


Reported history of child sexual abuse in schizophrenia: associations with heightened symptom levels and poorer participation over four months in vocational rehabilitation.
Cross-section research suggests reported childhood abuse in schizophrenia spectrum disorders is linked with graver symptom levels and social dysfunction. To examine this prospectively, we compared biweekly ratings of positive and emotional discomfort symptoms and weekly accounts of hours worked over 4 months of rehabilitation of 12 participants with schizophrenia or schizoaffective disorder and childhood sexual abuse history and 31 with schizophrenia or schizoaffective disorder and no childhood sexual abuse history. Repeated-measures ANOVA revealed the abuse group had consistently higher levels of both symptom components and poorer participation in vocational rehabilitation. A time by group effect was observed for hours of work, with the abuse group working increasingly fewer hours over time. Participants reporting abuse also were more likely to perform poorly on a test of executive function and to have particularly higher levels of hallucinations and anxiety over time. Clinical and theoretical implications are discussed.


Granular clinical history and outcome in 51 patients with primary and secondary malignant meningioma.
WHO grade III meningiomas, also known as malignant meningiomas (MMs), are rare, and the heterogenous clinical course in patients with MM is not well described. To characterize the clinical course of patients with MM, granular clinical data were gathered from 51 patients treated at the Department of Neurosurgery and Radiation Oncology, Rigshospitalet, in Copenhagen, Denmark, between 2000 and 2020. The authors investigated outcome and timing in terms of 1) tumor progression and grade transformation in patients previously diagnosed with WHO grade I or II meningiomas (patients with a secondary MM [sMM]); 2) performance status and complications following surgery; and 3) transition to noncurative treatment and ultimately death. Complications, time between recurrences, and outcome (modified Rankin Scale [mRS] score) for every surgery were analyzed, both malignant and premalignant. Of the 51 patients, 24 (47%) had an sMM. The time to WHO grade III transformation in the sMM group varied widely (median 5.5 years, range 0.5-22 years), but after transformation to a WHO grade III tumor, patients with an sMM and those with a primary MM (pMM) did not differ significantly in overall survival and cumulative risk of progression. Median overall survival for all 51 patients was 4.2 years (95% CI 2.6-7.2 years). Time from the decision to shift from curative to noncurative treatment until death was 3.8 months and the 30-day mortality rate following surgery was 11.8%. From a cumulative number of 151 surgeries, 10 surgeries were followed by improvement on the mRS, mRS score was unchanged in 70, and it worsened in 71. The MM was the underlying cause of death in 30 of 31 patients who had died at the end of follow-up. Together, these findings clearly show a significant morbidity and mortality from the disease itself and from the treatment. These findings warrant studies of prognostic factors for earlier support and adjuvant measures in MM and identify a need for better palliative strategies in this patient group.


Older patients' aversion to antidepressants. A qualitative study.
Depression is common among older patients yet is often inadequately treated. Patient beliefs about antidepressants are known to affect treatment initiation and adherence, but are often not expressed in clinical settings. To explore attitudes toward antidepressants in a sample of depressed, community-dwelling elders who were offered treatment. DESIGN. Cross-sectional, qualitative study utilizing semi-structured interviews. Primary care patients age 60 years and over with depression, from academic and community primary care practices of the University of Pennsylvania Health System and the Philadelphia Department of Veterans Affairs. Patients participated in either the Prevention of Suicide in Primary Care Elderly: Collaborative Trial or the Primary Care Research in Substance Abuse and Mental Health for the Elderly Trial. Sixty-eight patients were interviewed and responses from 42 participants with negative attitudes toward medication for depression were analyzed. Interviews were audiotaped, transcribed, and entered into a qualitative software program for coding and analysis. A multidisciplinary team of investigators coded the transcripts and identified key features of narratives expressing aversion to antidepressants. Four themes characterized resistance to antidepressants: (1) fear of dependence; (2) resistance to viewing depressive symptoms as a medical illness; (3) concern that antidepressants will prevent natural sadness; (4) prior negative experiences with medications for depression. Many elders resisted the use of antidepressants. Patients expressed concerns that seem to reflect their concept of depression as well as their specific concerns regarding antidepressants. These findings may enhance patient-provider communication about depression treatment in elders.


Effect of Psychological Nursing Intervention on Abnormal-Induced Labor of Fetus during Puerperium: Study on the Effects of Anxiety, Depression, and Life Events.
To study the effects of psychological nursing intervention on anxiety, depression, and life events in puerperal women with fetal abnormalities. From January 2020 to January 2022, eighty women with abnormal fetal induction and puerperium-treated were selected in our hospital as the subjects. The research group (n = 40) and control group (n = 40) were arbitrarily selected from 80 women with abnormal fetal induction and puerperium. The research group was given psychological nursing intervention based on routine nursing, and the control cases were given routine nursing. The scores of Generalized Anxiety Scale (GAD-7), Patient Health Questionnaire (PHQ-9), Event Impact Scale (IES-R), Life Events Scale (LES), and Newcastle Nursing Satisfaction Scale (NSNS) were studied before nursing and 4 weeks after discharge. Four weeks after discharge, the score of GAD-7 in the research group was lower, and the difference was statistically significant (P < 0.05). The score of PHQ-9 in the research group was lower, and the difference was statistically significant (P < 0.05). The IES-R score of the research group was lower, and the difference was statistically significant (P < 0.05). The LES score of the research group was lower, and the difference was statistically significant (P < 0.05). And the NSNS score of the research group was higher, and the difference was statistically significant (P < 0.05). The value of psychological care interventions in women with abnormally induced labor is more remarkable, contributing to the reduction of anxiety and depression and increasing the satisfaction of care for women with abnormally induced labor.


Restoration of miR-7 expression suppresses the growth of Lewis lung cancer cells by modulating epidermal growth factor receptor signaling.
microRNAs are an abundant class of short endogenous non-coding RNAs that function as important regulators of multiple target genes and participate in diverse biological roles in carcinogenesis. However, the role of miR-7 in lung cancer remains unclear and requires further elucidation. In the present study, we found a reduction of miR-7 expression in Lewis lung cancer (3LL) cells originating from mice by real-time RT-PCR. Restoration of miR-7 inhibited 3LL cell proliferation, induced cell apoptosis in vitro and reduced tumorigenicity in vivo. We further confirmed that miR-7 downregulated the expression of both epidermal growth factor receptor (EGFR) and murine leukemia viral oncogene homologue-1 (RAF-1) oncogenes by real-time PCR and western blot analysis. Furthermore, inhibition of EGFR showed similar effects to miR-7 enforcement in 3LL cells. Taken together, these findings revealed that miR-7 acts as an antitumor miRNA in 3LL by targeting and suppressing the expression of both EGFR and RAF-1 oncogenes. This study may provide a rationale for the use of miR-7 in lung cancer target therapy.


Carbohydrate-specific antibodies in normal human sera. I. Characterization of specificity for beta-D-glucose.
A glucose-dependent hemagglutinin, present in the serum of an apparently healthy donor, is shown to be a polyclonal IgM immunoglobulin with specificity for beta-D-glucopyranose configuration. The antibody did not agglutinate erythrocytes coated with hexoses differing from glucose at C2, C3, or C4 positions or lacking the primary alcohol group at C6 position. The hemagglutination reaction, quantitated in a continuous flow system, was inhibited by the addition of 6-deoxyglucose, 5-thioglucose, 2-deoxyglucose, 2-aminoglucose or 3-0 methylglucose. D-glucose, in beta- but not in alpha-configuration, attached by a glycosidic bond to another glucose or to an aglycone, was also inhibitory. A cross-reactivity was demonstrated between glucose and 6-deoxyglucose by antibody absorption and elution techniques. The donor's serum contained independent antibodies that reacted with erythrocytes coated with melibiose, gentiobiose, cellobiose, or N-acetylmannosamine. Further investigation revealed that antibodies are present in sera of all normal adults against erythrocytes coated with melibiose and N-acetylmannosamine and with high frequency against erythrocytes coated with gentiobiose, L-rhamnose, cellobiose, D-mannose, lactose, or D-galactose.


Oxygen effects on photosynthesis and C metabolism in desert plants.
The effect of 1% and 21% O(2) upon (14)CO(2) assimilation by desert plants exposed for 10 to 90 seconds has been studied. The plants studied can be divided into three groups with respect to O(2). The C(3) plants display the usual Warburg effect. No changes could be observed in the intensity of photosynthesis as a function of O(2) content in another group of plants (showing signs of Crassulacean acid metabolism). In still another group of plants (C(4) plants) the stimulating effect of O(2) on photosynthesis could be detected. In C(3) plants, O(2) inhibits the processing of carbon through the Calvin cycle intermediates. The involvement of carbon in the glycolate pathway fails to explain completely the inhibiting effect of O(2) on photosynthesis. It is assumed that O(2) inhibits the enzymes of the Calvin cycle. In C(4) plants O(2) stimulates the incorporation of (14)C into malate and aspartate. The incorporation of (14)C into the intermediates of the Calvin cycle in C(4) plants is inhibited much like that in typical C(3) plants.


Fracture risks in patients with atrial fibrillation treated with different oral anticoagulants: a meta-analysis and systematic review.
evidence on the difference in fracture risks for patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs) versus warfarin remains controversial. We aim to compare the fracture risks between the DOAC and warfarin prescriptions among the AF patients. we systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science up to 19 April 2021 for relevant studies. And the observational studies regarding the relationship between the DAOC versus warfarin prescriptions and fracture risks among the patients with AF were included in this meta-analysis. Two investigators independently screened the articles and extracted the relevant data. A random- or fixed-effect model was applied to calculate the pooled hazard ratio/relative ratios with 95% confidence intervals of fracture risks associated with the DOAC and warfarin prescriptions. Six studies comprising 351,208 patients and 9,424 fractures were included in this meta-analysis. Overall, the AF patients treated with DOACs tend to present a lower risk of any fracture compared with those treated with warfarin (relative ratio: 0.82, 95% confidence interval (CI): 0.74-0.91). Sub-analyses for each individual DOAC indicate that apixaban and rivaroxan are associated with lower risk of any fracture compared with warfarin (HR: 0.75, 95% CI: 0.60-0.92, and HR: 0.79, 95% CI: 0.71-0.88, respectively). this meta-analysis suggests that DOAC users have a lower risk of fractures than the warfarin users. The results of this study may provide optimal anticoagulation opportunities for AF patients with high fracture risk factors.


Self-reported cardiovascular conditions are associated with falls and syncope in community-dwelling older adults.
with increasing age, causes of syncope are more often of cardiac origin. Syncope in older persons is often mistaken for falls. Data regarding the association between specific cardiovascular conditions, falls and syncope are limited. cross-sectional analyses within a population sample aged 50+ (n = 8,173). Syncope and falls in the past year, cardiovascular conditions and co-variates were gathered through personal interviews. Associations between cardiovascular conditions and (recurrent) falls and syncope were studied through multivariable logistic regression. mean age was 64 years (range: 51-105); 54% was female. Four per cent reported syncope, 19% falls and 23% cardiovascular morbidity. Abnormal heart rhythm was associated with falls (odds ratio (OR) 1.3 [95% confidence interval (CI) 1.0-1.5]), syncope (OR 1.6 [1.2-2.3]) and recurrent syncope (OR 2.2 [1.3-3.6]). Heart murmur was associated with falls (OR 1.4 [1.1-1.8]), recurrent falls (OR 1.5 [1.0-2.0]) and syncope (OR 1.9 [1.3-2.7]). Angina was associated with recurrent falls (OR 1.4 [1.0-1.9]), syncope (OR 1.8 [1.2-2.6]) and recurrent syncope (OR 2.7 [1.6-4.6]). Heart failure was associated with recurrent falls (OR 1.9 [1.0-3.4]) and myocardial infarction with syncope (OR 1.5 [1.0-2.3]). self-reported cardiovascular conditions are associated with falls and syncope in a general population cohort. This warrants additional cardiovascular evaluation in older patients with unexplained falls and syncope.


Effects of plant growth substances on rooting of Hedychium spicatum under different temperature regimes.
Present study was carried out to develop a simple and efficient vegetative propagation protocol by applying various treatments to rhizome cuttings with different test solutions of auxins and phenolic compound. These were alpha-naphthalene acetic acid (NAA), Indole-3-butyric acid (IBA), Indole Acetic Acid (IAA), phloroglucinol and coumarin. The concentrations for each treatment were 10.0, 50.0 and 100.0 microM. After treatments the rhizome cuttings were planted in polybags containing forest soil and kept under different temperature regimes i.e., inside polyhose (at 20-25 degrees C), inside mist chamber (at 15-20 degrees C) and under nethouse (nursery condition, at 14-18 degrees C). The maximum rooting percentage (74.06%) was achieved at 20-25 degrees C (inside polyhouse) by applying 50.0 microM IBA. Inside poly house condition, the various developmental parameters showed better responses compare to other conditions. On the basis of present study emphasizes that the temperature play a crucial role in rooting and further growth of the plants in this species. By using this simple and significant conventional method of propagation we could be propagate this vulnerable medicinal and aromatic species at large scale for commercial purpose.


Apparatus for home monitoring of pregnant hypertensive patients.
A simple, convenient to use apparatus suitable for patient self-monitoring is described and illustrated with graphs of mean arterial pressure determinants which provide clinically useful hemodynamic details unobtainable with cuff blood pressure measurements. A bathroom scale and a forearm cuff blood pressure system completes the home monitoring apparatus.


HLA epitopes detected by serology.
There is evidence that many of the so-called multispecific cytotoxic antisera react to the amino acid-defined epitopes of the HLA-A and B loci molecules. This evidence is based on the finding that a group of sera produced allelic reactions which corresponded to amino acid substitutions. Antisera for 29 amino acid variants were identified at 67 variable residues on the A locus and for 17 of the 51 variable sites on the B locus. The results were validated by showing that the reactions produced by testing cells from 111 individuals on an epitope typing tray fit the Hardy Weinberg equilibrium. This means that the alleles defined by the antisera behaved as alleles in the random population. Tests of homozygous cells on the epitope typing trays produced completely mutually exclusive reaction patterns as expected on the basis of the amino acid substitutions. Two examples are cited in which immunization across a single HLA "antigen" difference existed between donor and recipient, resulting in a "multispecific" antiserum. The specificities contained in the serum exactly fit an amino acid difference between the donor and recipient.


Validity of screening for glaucomatous optic nerve damage using confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph II) in high-risk populations: a pilot study.
To evaluate whether confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph II [HRT II], Heidelberg Engineering, Heidelberg, Germany) is a valid tool for the detection of glaucomatous optic nerve damage. Observational, cross-sectional, nonconsecutive study in Montreal, Canada. Three hundred three nonconsecutive, high-risk persons were enrolled during a 6-month period. Participants underwent HRT II testing and a standard ophthalmologic examination, including gonioscopy, intraocular pressure measurement, and optic disc grading. Positive likelihood ratio (PLR) and negative likelihood ratio (NLR), sensitivities and specificities, positive predictive value (PPV) and negative predictive value (NPV), and kappa coefficients of agreement of Moorfields regression analysis (MRA), cup shape measure (CSM), height variation contour (HVC), and mean retinal nerve fiber layer thickness (MRNFL). Three hundred three participants were enrolled, and 291 were examined clinically; 21 (7.2%) were found to have glaucoma. Heidelberg Retina Tomograph II testing was performed successfully and was of acceptable quality in 531 of 601 eyes (88%). When MRA was compared with the clinically based diagnosis, the weighted kappa coefficient was kappa = 0.567 (95% confidence interval [CI], 0.42-0.71) for the right eye and kappa = 0.516 (95% CI, 0.37-0.66) for the left eye. Best kappa coefficient of agreement was seen when normals were grouped with suspects in both clinical and MRA diagnosis (kappa = 0.604; 95% CI, 0.409-0.799 in the right eye). Depending on the gold standard and test-positive definitions for glaucoma, specificity ranged from 87% to 97%, sensitivity from 25% to 100%, PPV from 28% to 68%, NPV from 84% to 100%, PLR from 5.0 to 19.2, and NLR from 1.3 to 6.2. When CSM, HVC, and MRNFLT were compared with clinical diagnosis, all outcome measures were found to have lower ranges: specificity from 46.9% to 83.7%, sensitivity from 36.5% to 76.9%, PPV from 6% to 36%, NPV from 80% to 99%, PLR from 0.8 to 4.0, NLR from 0.9 to 3.0. The results of this study suggest that a glaucoma screening program may be effective in detecting glaucoma when targeting high-risk populations. Heidelberg Retina Tomograph II testing may prove to be a useful tool in detecting glaucomatous optic nerve damage and could be used as part of a complete glaucoma screening protocol.


Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity.
Epigenetic silencing of tumor suppressor genes in human cancers is associated with aberrant methylation of promoter region CpG islands and local alterations in histone modifications. However, the mechanisms that drive these events remain unclear. Here, we establish an important role for histone H4 lysine 16 acetylation (H4K16Ac) and the histone acetyltransferase hMOF in the regulation of TMS1/ASC, a proapoptotic gene that undergoes epigenetic silencing in human cancers. In the unmethylated and active state, the TMS1 CpG island is spanned by positioned nucleosomes and marked by histone H3K4 methylation. H4K16Ac was uniquely localized to two sharp peaks that flanked the unmethylated CpG island and corresponded to strongly positioned nucleosomes. Aberrant methylation and silencing of TMS1 was accompanied by loss of the H4K16Ac peaks, loss of nucleosome positioning, hypomethylation of H3K4, and hypermethylation of H3K9. In addition, a single peak of histone H4 lysine 20 trimethylation was observed near the transcription start site. Down-regulation of hMOF or another component of the MSL complex resulted in a gene-specific decrease in H4K16Ac, loss of nucleosome positioning, and silencing of TMS1. Gene silencing induced by H4K16 deacetylation occurred independently of changes in histone methylation and DNA methylation and was reversed on hMOF reexpression. These results indicate that the selective marking of nucleosomes flanking the CpG island by hMOF is required to maintain TMS1 gene activity and suggest that the loss of H4K16Ac, mobilization of nucleosomes, and transcriptional down-regulation may be important events in the epigenetic silencing of certain tumor suppressor genes in cancer.


Coronary artery phenotypes in subjects with negative myocardial perfusion imaging and typical angina pectoris.
Limited data are available on coronary lesion morphology for patients with false-negative radionuclide findings together with typical angina symptoms. The study group consisted of 25 subjects with a negative pharmacological thallium (Tl)-201 single-photon emission computed tomography perfusion imaging study but typical angina symptoms and coronary artery disease (CAD) confirmed by coronary angiography. The control group included 690 subjects with a positive pharmacological Tl-201 single-photon emission computed tomography study and CAD. The study group showed a significantly older and higher female ratio than the control group. Significant differences were found between the 2 groups in the presence of current smoking status and hypertension. A noticeably higher percentage of positive metabolic syndrome ratio, number of metabolic syndrome components, high waist-to-hip ratio percentage and high waist circumference percentage in the study group. The study group was noticeably lower in mean numbers of culprit vessel involvement and mean lesion numbers than the control group. There were more individuals with type A classification and a lower proportion of complex stenoses--which contain type B2 and C lesions--in the study group than in the control group. The study group had significantly fewer calcified stenoses and complex morphology stenoses--the latter of which include lesion morphologies with chronic total occlusion, diffuse and calcification--than the control group. For the high probability of CAD lesions that requires interventional therapy, patients with negative myocardial scintigraphy but typical angina symptoms would be beneficial to intensive medical treatment and coronary study.


Martha Aeava v. Oa Heupu, 28 February 1986.
The Court held that a husband cannot be ordered to pay maintenance to his former wife under the Deserted Wives and Children Act of Papua New Guinea if their marriage was dissolved according to customary law. It ruled that the question of maintenance would have to be governed by customary law. It noted that, under customary law, it would be most unusual for a husband to have to pay maintenance and that a wife's relatives usually took on that obligation.


Assessment of novel tobacco heating product THP1.0. Part 6: A comparative in vitro study using contemporary screening approaches.
Cigarette smoking is a major risk factor for many adverse health conditions. Novel tobacco heating products (THPs) heat tobacco, reducing exposure to many of the harmful combustion toxicants in conventional cigarette emissions. In vitro studies have been employed to support the toxicological evaluation of chemicals and complex mixtures, including cigarette smoke. The use of automated robotics platforms for in vitro toxicological screening complements traditional testing approaches. Multiparametric toxicity and oxidative stress endpoints were used to assess in vitro biological responses elicited after exposure to total particulate matter (TPM) from two commercially available THPs, and the reference tobacco product 3R4F, in human bronchial epithelial cells. A luciferase-based reporter gene assay was used to assess antioxidant response element (ARE) transcriptional activation in stably transfected H292 cells after 6 and 24 h exposures. High-content screening was used to assess 10 endpoints normal human bronchial epithelial cells after 4 or 24 h exposures. 3R4F TPM stimulated significant increases in ARE activation (p < 0.005) and moderate activity in HCS cell-based assays compared to THP at comparable doses. THPs showed little or no activity in all assays. HCS techniques can extend safety assessments providing information quickly in the early stages of product innovation and development.


Essential Oils from Annonaceae Species from Brazil: A Systematic Review of Their Phytochemistry, and Biological Activities.
The present work involves a systematic review of the chemical composition and biological effects of essential oils from the Annonaceae species collected in Brazil from 2011 to 2021. Annonaceae is one of the most important botanical families in Brazil, as some species have economic value in the market as local and international fruit. In addition, the species have useful applications in several areas-for instance, as raw materials for use in cosmetics and perfumery and as medicinal plants. In folk medicine, species such as Annona glabra L. and Xylopia sericea A. St.-Hil. are used to treat diseases such as rheumatism and malaria. The species of Annonaceae are an important source of essential oils and are rich in compounds belonging to the classes of mono and sesquiterpenes; of these compounds, α-pinene, β-pinene, limonene, (E)-caryophyllene, bicyclogermacrene, caryophyllene oxide, germacrene D, spathulenol, and β-elemene are the most abundant. The antimicrobial, anti-inflammatory, antileishmania, antioxidant, antiproliferative, cytotoxic, larvicidal, trypanocidal, and antimalarial activities of essential oils from the Annonaceae species in Brazil have been described in previous research, with the most studies on this topic being related to their antiproliferative or cytotoxic activities. In some studies, it was observed that the biological activity reported for these essential oils was superior to that of drugs available on the market, as is the case of the essential oil of the species Guatteria punctata (Aubl.) R. A. Howard., which showed a trypanocidal effect that was 34 times stronger than that of the reference drug benznidazol.


Recruitment of Rad51 and Rad52 to short telomeres triggers a Mec1-mediated hypersensitivity to double-stranded DNA breaks in senescent budding yeast.
Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of telomerase. In both mammalian tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative recombination mechanism. Here we demonstrated that the budding yeast Saccharomyces cerevisiae type I survivors derived from telomerase-deficient cells were hypersensitive to DNA damaging agents. Assays to track telomere lengths and drug sensitivity of telomerase-deficient cells from spore colonies to survivors suggested a correlation between telomere shortening and bleomycin sensitivity. Our genetic studies demonstrated that this sensitivity depends on Mec1, which signals checkpoint activation, leading to prolonged cell-cycle arrest in senescent budding yeasts. Moreover, we also observed that when cells equipped with short telomeres, recruitments of homologous recombination proteins, Rad51 and Rad52, were reduced at an HO-endonuclease-catalyzed double-strand break (DSB), while their associations were increased at chromosome ends. These results suggested that the sensitive phenotype may be attributed to the sequestration of repair proteins to compromised telomeres, thus limiting the repair capacity at bona fide DSB sites.


POEMS syndrome complicated by follicular lymphoma.
A 59-year-old woman presented with ascites and intraperitoneal lymph node swelling. Pathological examination of the lymph node revealed follicular lymphoma. After a lymph node biopsy, she developed atypical genital bleeding, multiple endocrine disorders, polyneuropathy with a high plasma level of vascular endothelial growth factor (VEGF), and was diagnosed with POEMS syndrome. Following administration of methyl prednisolone, ascites immediately decreased and her performance status improved; however, about 18 months later, renal failure occurred, and she died despite increased steroid dosage. Lymph node swelling is often found in POEMS syndrome; however, its histological appearance is not well known, and it is very rare to be concomitant with malignant lymphoma. Therefore, it is important to perform a lymph node biopsy and investigate it in relation with VEGF.


Regulation of Mammalian Gene Expression by Glucose.
Recent data suggest that cells from species as diverse as yeast and mammals may use similar mechanisms to detect changes in nutrient concentration. Here we review recent advances in understanding how glucose regulates gene transcription in mammals.


[Metastatic brain tumors from gastrointestinal cancer: an analysis of patient background and treatment results].
Metastatic brain tumors have become a critical issue in clinical management for patients with cancer. We retrospectively analysed features of 105 patients with metastatic brain tumors from gastrointestinal cancer, who underwent treatment in our institute between September, 2002 and December, 2010. Treatment strategy was individualized according to the patient's systemic and neurologic conditions, size and location of the brain metastases, and expectant systemic treatment through our cancer board. Treatment outcome was significantly better in patients with RTOG RPA class 2 than in those with class 3(8.6 months vs 3.5 months: p<0.05). Metastatic brain tumors were diagnosed at 6.3/13.1/15.7 months after diagnosis of metastatic lung tumors from esophagus/stomach/colon cancers respectively. A third of the patients with metastatic brain tumor from rectal cancer presented without evident lung metastasis. In conclusion, patients with brain metastasis from gastrointestinal cancers can achieve improvement in survival with early diagnosis and multidisciplinary individualized treatments.


Horizontal cells of the normal and dystrophic rat retina: a wholemount study using immunolabelling for the 28-kDa calcium-binding protein.
Immunocytochemistry with a monoclonal antibody against the 28-kDa calcium-binding protein (28-kDa CaBP) was used to study horizontal cells in both congenic control (RCS-rdy+) and dystrophic (RCS) 3-month-old rat retina. We found that horizontal cells in the RCS-rdy+ rat retinas were distributed evenly from the centre to the peripheral retina with a mean density of 783 cells mm-2. Cell size ranged between 6.5-12.5 microns in diameter with a mean of 8.87 microns. Individual cell processes could not be followed readily, however they formed a narrow plexus within the outer plexiform layer with the primary dendrites extending radially from each cell soma in an organized manner. In the RCS rat, by contrast, the horizontal cell processes were more disorganized than in the congenic controls. The degree of disorganization varied across the retina. In the posterior pole, where all outer layers had been lost, many processes were grossly swollen along their length and at the tips. The cell somas were also distributed more widely in the depth of the retina. In the peripheral retina, where a debris layer was still present, the processes were less swollen but they extended abnormally widely in depth. Despite the disorganized structure the mean and range of cell size (9.23 microns, 5.5-15.5 microns), and cell density (796 cells mm-2) were similar to that of the control RCS-rdy+ animals. These findings indicate that in dystrophic retinas beyond a certain stage of degeneration the horizontal cells become abnormal in their structure but are present at a normal density and the somas are not grossly swollen or shrunken.(ABSTRACT TRUNCATED AT 250 WORDS)


Intranodal papillary epithelial proliferations: a local process with a spectrum of morphologies and frequent association with papillomas in the breast.
Lymph nodes, particularly those draining in major anatomic sites like axilla, pelvis, and neck are potential sites for the occasional presence of ectopic tissue, usually representative of the organ being drained. Owing to the uncertainty surrounding the processes causing such findings, and particularly in the setting of lymph node dissection and sampling for cancer staging, intranodal epithelial inclusions, rare as they may be, might be fertile soil for overdiagnosis of metastatic disease. Intranodal papillary inclusions are particularly problematic and challenging because of their complex architecture that may easily mimic a metastasis. From the files of the Breast Consultation Service, Department of Pathology at the Vanderbilt University Medical Center in Nashville, we identified 6 cases in which histopathologic examination of axillary lymph nodes revealed intranodal papillary inclusions (papillary epithelial proliferations). One case showed atypical ductal hyperplasia, 1 showed low-grade ductal carcinoma in situ, and 1 showed usual ductal hyperplasia. The corresponding breast lesions were papillomas in 5 of 6 cases, 2 of which displayed atypical ductal hyperplasia, whereas 3 showed low-grade ductal carcinoma in situ. One case showed intermediate-grade invasive ductal carcinoma, and the associated intranodal papilloma lacked atypia. Our findings suggest that intranodal papillary proliferations are often, although not exclusively, associated with papillary and noninvasive breast neoplasms, hence highlighting the origin of these intranodal lesions as independent de novo nodal processes rather than metastatic deposits.


[Surgical treatment of basaliomas with calculated safety margin and control of the histologic borders. Experiences with 355 tumors].
An integrated concept for the surgical treatment of basal cell carcinoma is presented, which is based on individually calculated safety margins and modified microscopically controlled surgery. The individual calculation of the safety margin assumes there is a relationship between the clinically visible tumor diameter and subclinical infiltration; the calculation of the safety margin therefore is based on the size of the clinically visible portion of the basal cell carcinoma. Detection of subclinical infiltration and exclusion of the possibility of subtotal excision are ensured by routine histological control of the margins of the excised specimen. The surgical treatment of basal cell carcinoma presented in this study is considerably less time-consuming than other forms of microscopically controlled surgery. No recurrences have been observed after radical excision of basal cell carcinomas with this method.


Surgical teaching quality makes a difference.
This study examined the influence of the quality of faculty members' teaching on student performance in a third-year surgery clerkship. Eighty-nine third-year students on a surgery clerkship completed preceptor evaluation forms. The faculty member's overall score was the mean of ratings from all the third-year students for whom that faculty member served as preceptor during the year. We examined associations between these ratings and student performance on the National Board of Medical Examiners (NBME) surgery subject examination and clerkship Objective Structured Clinical Examination (OSCE) by using an analysis of covariance that controlled for prior academic achievement [United States Medical Licensure Examination (USMLE) Part I]. The average mean teaching evaluation score was associated with the scores on the NBME surgery subject examination (P = 0.0005). Students with attendings who received poor teaching evaluations performed more poorly on OSCE data-gathering stations than did students with attendings rated as average or good. The study results indicate that the teaching quality of surgery faculty appears to have an impact on student performance.


A 3D ontogenetic atlas of Alligator mississippiensis cranial nerves and their significance for comparative neurology of reptiles.
Cranial nerves are key features of the nervous system and vertebrate body plan. However, little is known about the anatomical relationships and ontogeny of cranial nerves in crocodylians and other reptiles, hampering understanding of adaptations, evolution, and development of special senses, somatosensation, and motor control of cranial organs. Here we share three dimensional (3D) models an of the cranial nerves and cranial nerve targets of embryonic, juvenile, and adult American Alligators (Alligator mississippiensis) derived from iodine-contrast CT imaging, for the first time, exploring anatomical patterns of cranial nerves across ontogeny. These data reveal the tradeoffs of using contrast-enhanced CT data as well as patterns in growth and development of the alligator cranial nervous system. Though contrast-enhanced CT scanning allows for reconstruction of numerous tissue types in a nondestructive manner, it is still limited by size and resolution. The position of alligator cranial nerves varies little with respect to other cranial structures yet grow at different rates as the skull elongates. These data constrain timing of trigeminal and sympathetic ganglion fusion and reveal morphometric differences in nerve size and path during growth. As demonstrated by these data, alligator cranial nerve morphology is useful in understanding patterns of neurological diversity and distribution, evolution of sensory and muscular innervation, and developmental homology of cranial regions, which in turn, lead to inferences of physiology and behavior.


Supported Ionic Liquid Silica as Curing Agent for Epoxy Composites with Improved Mechanical and Thermal Properties.
The present study aims to improve the mechanical properties of epoxy composite by incorporating supported ionic liquid silica (IL-silica). The IL-silica not only showed improved interfacial interaction and reinforcement, but also served as cure agent of epoxy composites. The differential scanning calorimetry analysis revealed that epoxy composites could be successfully cured with IL-silica without any routine curing agents. IL-silica/epoxy composites presented higher mechanical and thermal properties compared with epoxy composite containing un-functionalized silica (u-silica). The dynamic mechanical analysis showed that the storage modulus of composites significantly increased with the addition of IL-silica in comparison to that with added u-silica, as well as the variation of Tg parameter. The incorporation of IL-silica simultaneously enhanced the tensile strength, toughness, and thermal stability of the epoxy composites. The considerable improvements in mechanical and thermal properties are ascribed to the improved dispersion of IL-silica and the enhanced interfacial interactions between epoxy matrix and IL-silica by strong covalent bonding, which results in an effective load transfer.


Biodiversity and spatial distribution of epiphytic ferns on Alsophila setosa Kaulf. (Cyatheaceae) caudices in Rio Grande do Sul, Brazil.
The extractive exploitation of the tree fern Alsophila setosa Kaulf. alters forest formations and diminishes the availability of micro-habitat for epiphytes. A survey of epiphytic fern communities on A. setosa at 16 study sites in different forest formations in the State of Rio Grande do Sul, Brazil, documented the occurrence of 31 species representing 16 genera and six families. The greatest richness of species occurred in Polypodiaceae (39%) and in the genus Asplenium L. (22%). Habitual holoepiphyte was the predominant ecological category, representing 61% of the species. Similarity analysis demonstrated heterogeneity in the composition of the epiphytic ferns at the study sites and indicated that the vegetation type is not the main factor for floristic difference. The lowest total specific richness (5) was recorded for the seasonal deciduous forest site. The majority of the sites presented similar averages of phorophyte height and epiphyte richness per caudex. In 25% of the sites the height of the host plants presented significant correlation with specific richness. Considering that the majority of the epiphytes are habitual and that some of them occur exclusively or preferentially on tree ferns, the maintenance of these host plants in the vegetation is essential for the conservation of epiphytic species.


Tumour necrosis factor-alpha induces neutrophil-mediated injury of cultured human endothelial cells.
We investigated the ability of TNF-alpha to mediate damage of endothelial cells in the presence of neutrophils, by measuring detachment of cultured human umbilical vein endothelial cells (HUVEC). Endothelial cell detachment was increased from 5% to about 75% by the presence of 1-10 ng/ml TNF-alpha during incubation with neutrophils, whereas negligible endothelial cell lysis was observed as measured by 51Cr release. TNF-alpha was compared with the cytokines IL-1 alpha and IFN-gamma and with PMA and LPS. Both TNF-alpha and PMA appeared to be strong triggers for neutrophil-induced endothelial cell detachment, whilst reduced injury was seen after addition of IL-1 alpha and LPS. IFN-gamma did not induce endothelial cell detachment, but potentiated the effect of both TNF-alpha and IL-1 alpha. TNF-alpha-induced endothelial cell detachment was neutrophil dependent, since pre-incubation of neutrophils, but not pre-incubation of endothelial cells with TNF-alpha, caused endothelial cell detachment. Thus, TNF-alpha-induced increase in neutrophil-adhesiveness of HUVEC was found not to be essential for endothelial damage. Pre-incubation of neutrophils in suspension with TNF-alpha induced rapid activation, followed by nearly complete deactivation of neutrophils, as measured by their capacity to induce detachment of endothelial cells after removal of TNF-alpha. These results indicate that local presence of TNF-alpha might be critical in tissue or organ damage during early, neutrophil-mediated inflammatory processes, independent of enhanced adhesiveness of endothelium for neutrophils.


Fiber composition of the superior laryngeal nerve in rats and guinea pigs.
The fiber composition of the superior laryngeal nerve (SLN) which is served as the laryngeal afferent pathway was clarified in rats and guinea pigs. The proportions of the number of myelinated and unmyelinated fibers in the SLN were almost the same in both rats and guinea pigs. The unmyelinated fibers show the peak distribution of axon diameter ranging from 0.79 to 1.00 micron in both species, whereas the peak distribution of myelinated fibers ranged from 2.51 to 3.16 microns in rats and from 3.98 to 5.01 microns in guinea pigs. The mean axon diameter of unmyelinated fibers was significantly larger in rats (mean: 1.12 microns) than in guinea pigs (0.96 micron), whereas that of myelinated fibers was significantly larger in guinea pigs (4.04 microns) than in rats (3.30 microns). Such findings would reflect the cardiopulmonary reflexes elicited from the larynx in these animal species.


Transition-Metal-Free Radical C(sp3)-C(sp2) and C(sp3)-C(sp3) Coupling Enabled by 2-Azaallyls as Super-Electron-Donors and Coupling-Partners.
The past decade has witnessed the rapid development of radical generation strategies and their applications in C-C bond-forming reactions. Most of these processes require initiators, transition metal catalysts, or organometallic reagents. Herein, we report the discovery of a simple organic system (2-azaallyl anions) that enables radical coupling reactions under transition-metal-free conditions. Deprotonation of N-benzyl ketimines generates semistabilized 2-azaallyl anions that behave as "super-electron-donors" (SEDs) and reduce aryl iodides and alkyl halides to aryl and alkyl radicals. The SET process converts the 2-azaallyl anions into persistent 2-azaallyl radicals, which capture the aryl and alkyl radicals to form C-C bonds. The radical coupling of aryl and alkyl radicals with 2-azaallyl radicals makes possible the synthesis of functionalized amine derivatives without the use of exogenous radical initiators or transition metal catalysts. Radical clock studies and 2-azaallyl anion coupling studies provide mechanistic insight for this unique reactivity.


Non-homologous sex chromosomes of birds and snakes share repetitive sequences.
Snake sex chromosomes provided Susumo Ohno with the material on which he based his theory of how sex chromosomes differentiate from autosomal pairs. Like birds, snakes have a ZZ male/ZW female sex chromosome system, in which the snake Z is a macrochromosome much the same size as the bird Z. However, the gene content shows clearly that the snake and bird Z chromosomes are completely non-homologous. The molecular aspect of W chromosome degeneration in snakes remains largely unexplored. We used comparative genomic hybridization to identify the female-specific region of the W chromosome in representative species of Australian snakes. Using this approach, we show that an increasingly complex suite of repeats accompanies the evolution of W chromosome heteromorphy. In particular, we found that while the python Liasis fuscus exhibits no sex-specific repeats and indeed, no cytologically recognizable sex-specific region, the colubrid Stegonotus cucullatus shows a large domain on the short arm of the W chromosome that consists of female-specific repeats, and the large W of Notechis scutatus is composed almost entirely of repetitive sequences, including Bkm and 18S rDNA-related elements. FISH mapping of both simple and complex probes shows patterns of repeat amplification concordant with the size of the female-specific region in each species examined. Mapping of intronic sequences of genes that are sex-linked in both birds (DMRT1) and snakes (CTNNB1) reveals massive amplification in discrete domains on the W chromosome of the elapid N. scutatus. Using chicken W chromosome paint, we demonstrate that repetitive sequences are shared between the sex chromosomes of birds and derived snakes. This could be explained by ancestral but as yet undetected shared synteny of bird and snake sex chromosomes or may indicate functional homology of the repeats and suggests that degeneration is a convergent property of sex chromosome evolution. We also establish that synteny of snake Z-linked genes has been conserved for at least 166 million years and that the snake Z consists of two conserved blocks derived from the same ancestral vertebrate chromosome.


Pathogenic variants screening in five non-obstructive azoospermia-associated genes.
Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility and a recent, genome-wide association study (GWAS) has identified four risk loci associated with NOA. However, a large portion of the heritability of NOA has not been well explained by GWAS. By hypothesizing that rare, low-frequency and common genetic variants might point toward a causal relation between candidate genes and NOA, we performed a two-stage study including deep exon sequencing in 96 NOA cases and 96 healthy controls and a replication study in a larger population containing 522 NOA cases and 484 healthy controls. In the solexa sequencing stage, a total of two rare mutations (chr20. 1902132 and chr20. 1902301 in SIRPA), four common mutations (rs1048055 and rs2281807 in SIRPG, rs11046992 and rs146039840 in SOX5) were identified by using next generation sequencing (NGS). In the validation stage, subjects in the NOA group had a significantly decreased frequency of the heterozygous GA genotype in SIRPA (4.23%, 22 out of 520) than that in the control group (8.60%, 41 out of 477) [odds ratios (OR) 0.47, 95% confidence intervals (CI) 0.28-0.80] (P = 6.00 × 10(-3)). The rs1048055 in SIRPG was associated with a significantly increased risk of spermatogenic impairment, compared with the CC genotype (OR 3.93, 95% CI 1.59-9.70) (P = 3.00 × 10(-3)). Our study provides evidence of independent NOA risk alleles driven by variants in the protein-coding sequence of two of the genes (SIRPA and SIRPG) discovered by GWAS. Further investigation in larger populations and functional characterizations are needed to validate our findings.


Pristomyrmex tsujii sp. n. and P. mandibularis Mann (Hymenoptera, Formicidae) from Fiji.
Pristomyrmex tsujii sp. n., an endemic species of the Fiji islands, is described from the worker, ergatoid queen, alate queen and male castes. The alate queen and male castes of Pristomyrmex mandibularis Mann are also described for the first time. The ergatoid queens for both species appear to be morphologically intermediate between the worker and alate queen castes. Pristomyrmex tsujii is readily distinguished from Pristomyrmex mandibularis by the lack of well-developed propodeal spines. Although both species occur across the Fijian archipelago, they are rarely encountered and workers are most often collected from sifted litter. The descriptions are illustrated with specimen photographs, line drawings and a distribution map.


Sexually transmitted diseases and human immunodeficiency virus-discordant partnerships among men who have sex with men.
Sexually active men who have sex with men (MSM) at 5 Seattle clinics were assessed for bacterial sexually transmitted diseases (STDs), human immunodeficiency virus (HIV)-discordant partnerships, sexual behavior, and drug use. Of the HIV-positive men, 45% reported having HIV-negative sex partners and 42% reported having sex partners with unknown serostatus during the past 2 months, whereas 14% and 57% of HIV-negative men reported having HIV-positive and unknown-serostatus sex partners, respectively. Correlates of sex partners with unknown serostatus were recruiting sex partners at bathhouses or parks. Gonorrhea, chlamydia, or syphilis was diagnosed in 12% of HIV-positive and 13% of HIV-negative MSM, and the rates did not differ between men with HIV-concordant and HIV-discordant partnerships. High prevalences of bacterial STDs and HIV-discordant partnerships emphasize the need for interventions to foster serostatus discussion, condom use, fewer anonymous partners, and STD screening.


Factors Influencing Surgical Outcomes for Intradural Spinal Tumours: A Single-Centre Retrospective Cohort Study.
Introduction Intradural spinal tumours are relatively uncommon tumours of the central nervous system. In this study, we sought to assess our current practice and determine the factors which affect the surgical outcomes of intradural spinal tumour resection. Methods All consecutive patients who underwent surgical resection of intradural spinal tumours from December 2011 to November 2018 were retrospectively reviewed. The Modified McCormick Scale (MMS) was used to grade patients' neurological status both pre-operatively and at the latest follow-up. The associations between changes in MMS and variables such as patient demographics, tumour location, number and experience of consultants involved in the procedure, use of intraoperative neuro-monitoring, bony spinal exposure and dural closure methods were assessed. A multivariable binary logistic regression model was performed to identify independent predictors of improvements in MMS. All analyses were performed using IBM SPSS 22 (IBM Corp. Armonk, NY), with p<0.05 deemed to be indicative of statistical significance throughout. Results A total of 145 patients met the inclusion criteria, with a median age of 56.5 years; of whom 119 had extramedullary tumours and 26 had intramedullary tumours. Methods of dural closure were variable, and there was an increasing trend over time towards using the laminoplasty approach for bony exposure. Neither the experience of consultants (p=0.991) nor the number of consultants involved (p=0.084) was found to be significantly associated with the change in MMS, with the strongest predictor being the baseline MMS (p<0.001). Patients who had adjuvant therapy were also significantly more likely to have a poorer neurological outcome (p=0.001). Conclusion A good neurological baseline is a significant positive predictor of an improved functional outcome. The number and seniority of consultant surgeons involved in intradural spinal tumour resections did not significantly alter the postoperative outcomes of patients in our single-unit retrospective study.


Carcinoma of the gallbladder.
A retrospective study of 100 proved cases of primary carcinoma of the gallbladder admitted to the University Surgical Unit, University of Hong Kong, over a 20-year period was undertaken. The female to male ratio was 1.4 to 1. The peak incidence was in the seventh decade for the females and the sixth decade for the males. Preoperative diagnosis was made in 10 patients. "Curative" cholecystectomy was performed in 20 patients with a 5-year survival rate of 10 per cent. Palliative procedures were performed in 44 patients with a median survival of 8 weeks, which was not significantly different from that in the 30 patients who were not operated upon or had laparotomy and biopsy only. Radical resection was carried out in 6 patients, all of whom died in hospital. Gallstones were found in only 26 patients. The gallbladders of 3 patients had associated benign tumours, one of which had malignant transformation at multiple sites. One patient had chronic typhoid infection. The incidence of clonorchis infestation and primary pyogenic cholangitis in these 100 patients was not different from that of our general hospital population.


Health-related quality of life among patients with major depression.
The study compared health-related quality of life in 165 patients with major depression and 165 randomly selected and with age- and gender-matched controls from a population sample. Health-related quality of life was measured with the self-report questionnaire (RAND-36), which consists of eight dimensions. Overall, perceived quality of life was broadly reduced among depressive outpatients, and as compared with the control group, significant impairment was observed for all eight dimensions of health-related quality of life. Accompanying somatic diseases causing disability had no additional impact on the reduction of quality of life in depressive patients. Depression per se impairs an individual's functioning ability in a number of ways. It has a significant effect not only on mental well-being but also on perceived physical functioning and bodily pain, and even on general health perceptions. Major depression seems to explain the broad decline in the quality of life among depressive patients.


Axial Micromotion Locking Plate Construct Can Promote Faster and Stronger Bone Healing in an Ovine Osteotomy Model.
Fixing bone fractures with controlled axial interfragmentary micromotion improves bone healing; however, the optimal type of implant construct for this purpose is still lacking. The present study describes a novel axial micromotion locking plate (AMLP) construct that allows axial interfragmentary micromotion of 0.3 or 0.6 mm. We investigated whether the AMLP constructs enhance bone healing compared to an ordinary locking plate (LP) using an ovine osteotomy model. The stiffness of the constructs was tested under axial loading. We created a 3-mm osteotomy in the left hind leg tibia of sheep that was then stabilized with a 0.3- or 0.6-mm AMLP or LP construct (n = 6/group). Bone healing was monitored weekly by X-ray radiography starting from week 3 after surgery. At week 9, the specimens were collected and evaluated by computed tomography and torsional testing. We found that the AMLPs had a lower stiffness than the LP; in particular, the stiffness of the 0.6-mm AMLP construct was 86 and 41% lower than that of the LP construct for axial loads <200 and >200 N, respectively. In the in vivo experiments, tibial osteotomies treated with the 0.6-mm AMLP construct showed the earliest maximum callus formation (week 5) and the highest volume of bone callus (9.395 ± 1.561 cm3 at week 9). Specimens from this group also withstood a 27% greater torque until failure than those from the LP group (P = 0.0386), with 53% more energy required to induce failure (P = 0.0474). These results demonstrate that AMLP constructs promote faster and stronger bone healing than an overly rigid LP construct. Moreover, better bone healing was achieved with an axial micromotion of 0.6 mm as compared to 0.3 mm.


Ethylene Promotes the Capability To Malonylate 1-Aminocyclopropane-1-carboxylic Acid and d-Amino Acids in Preclimacteric Tomato Fruits.
When whole unripe green tomato fruits (Lycopersicon esculentum Mill, cv T(3)) were treated with ethylene (10 microliters per liter) for 18 hours, the fruit's ability to convert 1-aminocyclopropane-1-carboxylic acid (ACC) to N-malonyl-ACC (MACC) increased markedly and such an effect was also observed in fruits of mutant nor, which cannot ripen normally. The promotion of the capability to malonylate ACC by ethylene increased with the increasing ethylene concentration from 0.1 to 100 microliters per liter and with increasing duration of ethylene treatment up to 8 hours; a longer duration of ethylene treatment did not further increase the malonylation capability. When ethylene was withdrawn, the promotion disappeared within 72 hours. Norbornadiene, a competitive inhibitor of ethylene action, effectively eliminated the promotive effect of ethylene. Ethylene treatment also promoted the fruits' capability to conjugate d-amino acids and alpha-amino-isobutyric acid. Since the increase in the tissue's capability to malonylate ACC was accompanied by an increase in the extractable activity of ACC and d-amino acid malonyltransferase, ethylene is thought to promote the development of ACC/d-amino acid malonyltransferase in unripe tomato fruits.


[Evaluation of tumor marker CA15-3 in breast cancer].
CA15-3, a new tumor marker for breast cancer, was determined in various malignant diseases including breast cancer and various benign diseases, and its clinical significance and usefulness were studied. In 18 normal individuals, the value of CA15-3 was 8.9 +/- 3.3 U/ml (mean +/- SD). In primary breast cancer, the positivity was 20% for Stage I, 0% for Stages II and III and 100% for Stage IV. Of 17 cases of recurrent breast cancer, 13 (77%) were shown to be positive. The therapeutic effect and the value of CA15-3 were well correlated with each other. As for other malignant tumors, positive cases were observed in 50% of recurrent cancer of the stomach and in 14% of malignant tumors of the biliary system. All of these cases were terminal-stage cancers. The CEA value determined simultaneously showed a good correlation, r = 0.87 (p less than 0.01) with CA15-3 in malignant tumors other than breast cancer. In breast cancer, however, the correlation between the two was low, r = 0.18. These results suggest that CA15-3 is not necessarily useful in the diagnosis of primary breast cancer, but is useful as an indicator of the effect of therapy for recurrent breast cancer and for the prediction of recurrence.


Glycosylated haemoglobin levels in children with protein-energy malnutrition.
Fasting blood glucose, serum protein and glycosylated haemoglobin level (HbA1c) were determined in 50 children (aged 1-5 years) suffering from protein-energy malnutrition and in 25 healthy and nutritionally normal children of the same age group. It was observed that HbA1c correlated well with the blood glucose values of the children. It was also observed that they had significantly higher values of HbA1c than the controls, indicating the existence in them of glucose intolerance. Long-term monitoring of the glycaemic status is therefore suggested as a means of assessing any relationship between glycosylated haemoglobin and impaired pancreatic function in such patients.


Psychological impact of islet cell antibody screening.
The purpose of this study was to evaluate the psychological impact of autoantibody screening and its results on at-risk individuals and family members. Individuals who were antibody positive (AP) were identified through a large-scale screening program conducted at our institute. The sample consisted of nine families in whom 10 AP youngsters (7 M, 3 F) were identified, ranging in age from 6-18 years (mean 11.8, median 10 yr). Seventeen parents and eight diabetic youngsters (mean age 15.2, median 16 yr) participated in the study. Reaction to autoantibody positivity was assessed with the Impact of Event scale (IES). The IES was answered twice: within a week from the disclosure of the AP status, and 3 months later. Parents scored higher than their diabetic children and AP children on both measures of the IES, Intrusion and Avoidance. Three months later both scores were significantly reduced in both the parents and the AP children; however, parents still scored significantly higher on both scores than the AP children. The results suggest that learning one's AP status induces significant anxiety, especially in parents of AP youngsters. Although this initial anxiety dissipates over time it still remains quite high after 3 months. The results highlight the importance of psychosocial counseling for all members of diabetes mellitus screening and prevention trials.


Characterisation of cytokine mRNA expression in tumour-infiltrating mononuclear cells and tumour cells freshly isolated from human colorectal carcinomas.
The in situ function of tumour-infiltrating leukocytes (TIL) in human colorectal adenocarcinoma (CRC) is unclear. Local cytokine expression probably regulates the anti-tumour immune response and tumour immune surveillance. We examined the distribution of mRNA for IFN-gamma, TNF-alpha, IL-10 and IL-4 in TIL, and tumour cells freshly isolated from 21 surgically removed primary CRC, using a semiquantitative RT-PCR. Lamina propria-infiltrating leukocytes (LPL) and epithelial cells from normal colon mucosa of 10 CRC patients served as negative controls. Median levels of IFN-gamma and TNF-alpha mRNA were higher in TIL than LPL (p = 0.0002 and 0.0001). IL-10 mRNA was generally observed in TIL and LPL, but no or very small amounts of IL-4 transcripts were detected in TIL and LPL. TNF-alpha and IL-10 mRNA were more abundant in colorectal tumour cells than in the normal epithelial cells (p = 0.0136 and 0.0036). The number of IFN-gamma transcripts in TIL correlated negatively (p = 0.039) and the number of TNF-alpha transcripts in tumour cells correlated positively with the Dukes' stages (p = 0.0147). Our results suggest that TIL are characterized by a type 1 (Th1/Tc1-like) pattern of cytokine expression and function as T cells (and macrophages) in the local, cell-mediated anti-tumour immune response in early stages of CRC. Changes in IFN-gamma and TNF-alpha mRNA in TIL and tumour cells could be related to tumour progress (e.g. by T cell anergy) or forming of metastases, respectively.


Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors.
The purpose of this study was to assess the long-term outcomes of patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) without Five-Factor Score (FFS)-defined poor-prognosis factors (FFS=0) and enrolled in a prospective clinical trial. Patients were followed (2005-2012) under routine clinical care in an extended study and data were recorded prospectively. Long-term survival, disease-free survival (DFS), relapses, therapeutic responses and sequelae were analyzed. Mean±SD follow-up was 98.2±41.9months. After having initially received glucocorticoids (GC) alone, according to the study protocol, 82% (97/118) patients achieved remission but 18% (21/118) required ≥1 immunosuppressant(s) (IS) before 19/21 achieved remission. Two patients died before entering remission. After remission, 53% (61/116) patients relapsed 25.6±27.9months after starting treatment. The 5- and 8-year overall survival rates were 93% and 86%, respectively, with no difference between PAN and MPA, and between relapsers and nonrelapsers. DFS was shorter for MPA than PAN patients (P=0.02). Throughout follow-up, 47% of patients required ≥1 IS. At the last follow-up visit, 44% were still taking GC and 15% IS. The mean vasculitis damage index score was 1.9±1.9; the most frequent sequelae were peripheral neuropathy, hypertension and osteoporosis. For PAN or MPA patients without poor-prognosis factors at diagnosis and treated initially with GC alone, long-term survival was excellent. However, relapses remained frequent, requiring IS introduction for nearly half of the patients. To lower the frequencies of relapses and sequelae remains a challenge for FFS=0 PAN and MPA patients.