DMRT1 is a testis-determining gene in rabbits and is also essential for female fertility.
DMRT1 is the testis-determining factor in several species of vertebrates, but its involvement in mammalian testes differentiation, where SRY is the testis-determining gene, remains ambiguous. So far, DMRT1 loss-of-function has been described in two mammalian species and induces different phenotypes: Disorders of Sex Development (46, XY DSD) in men and male infertility in mice. We thus abolished DMRT1 expression by CRISPR/Cas9 in a third species of mammal, the rabbit. First, we observed that gonads from XY DMRT1-/- rabbit fetuses differentiated like ovaries, highlighting that DMRT1 is involved in testis determination. In addition to SRY, DMRT1 is required in the supporting cells to increase the expression of the SOX9 gene, which heads the testicular genetic cascade. Second, we highlighted another function of DMRT1 in the germline since XX and XY DMRT1-/- ovaries did not undergo meiosis and folliculogenesis. XX DMRT1-/- adult females were sterile, showing that DMRT1 is also crucial for female fertility. To conclude, these phenotypes indicate an evolutionary continuum between non-mammalian vertebrates such as birds and non-rodent mammals. Furthermore, our data support the potential involvement of DMRT1 mutations in different human pathologies, such as 46, XY DSD as well as male and female infertility.


Blepharochalasis with multiple system involvement.
A rare case of bilateral blepharochalasis of the upper eyelids is presented in a 10-year-old boy with several systemic abnormalities--unilateral agenesis of the left kidney, multiple skeletal anomalies of the vertebral column, and congenital heart disease with a left to right shunt. Such widespread congenital defects in association with blepharochalasis have not been described before. Blepharochalasis may represent a part of a more generalised disorder.


Dietary intake of trace elements and minerals among adults in underprivileged communities of rural Rajasthan, India.
In developing countries, data on dietary intake of trace elements, and even major elements, is limited. The dietary intake of 1277 adults of underprivileged communities of rural Rajasthan was studied. Intake was assessed by the 24-h dietary recall method from which the average daily intake of macronutrients, some major elements, and trace elements was computed. The zinc intake was 69.7 and 49.7% of the recommended daily allowance in males and non-pregnant non-lactating females, respectively. The intakes of manganese and molybdenum were adequate when compared with the suggested daily intakes. Element intake during the physiological stress conditions of pregnancy and lactation was 42.4 and 53.0% for zinc, 36.5 and 29.8% for copper, and 21.0 and 23.1% for calcium, respectively. The intake of iron was less than 20 mg/day for all female subjects studied. No significant difference was observed in the trace element intake of subjects with different grades of malnutrition. Assessment of dietary intake may provide a useful indication of the possible status of major and trace elements among adult subjects.


Relationship between atrophy of the amygdala and ictal fear in temporal lobe epilepsy.
Viscerosensory and affective manifestations are often elicited by temporal lobe seizure discharges. They have been reproduced by amygdaloid stimulation in awake patients during stereotaxic exploration or neurosurgical procedures. They are not exclusively reproduced by stimulation of the amygdala, though most commonly they are evoked from it. Ictal fear is frequently, but not invariably, associated with a rising epigastric sensation, palpitations, mydriasis and pallor. We studied 50 patients (mean age 33 years) with intractable temporal lobe epilepsy (TLE): MRI volumetric measurements of amygdala and hippocampus were performed using a protocol previously described by our group (Watson et al., Neurology 1992; 42: 1743-50). All patients had extensive EEG investigation and at least two seizures recorded by video-EEG monitoring. Seventeen patients (34%) had a clear history of fear accompanied by a rising epigastric sensation as the initial manifestation of their habitual attacks. The amygdala volumes in this group were significantly (P = 0.001) smaller (mean 2131.6 mm3) compared with the volumes of the 33 patients without these symptoms (mean 2561.5 mm3). Both patient groups had smaller mean amygdala volumes compared with normal controls (mean 2828.2 mm3). Postoperative pathology correlated well with volumetric atrophy. In addition, we found that patients with more pronounced amygdaloid atrophy more commonly had prolonged febrile convulsions in early childhood and also more frequently secondarily generalized seizures. Results support the finding that ictal fear is related to pathology of the amygdala and that it, like the hippocampus, is an important substrate of TLE.


Dual-Switching Electrochromism and Electrofluorochromism Derived from Diphenylamine-Based Polyamides with Spirobifluorene/Pyrene as Bridged Fluorescence Units.
Electrochromic (EC)/electrofluorochromic (EFC) bifunctional materials are receiving great attention because of their promising applications in optoelectronic devices. However, the development of ideal EC/EFC bifunctional materials is still a great challenge because of the poor integration of EC/EFC performances (optical contrast, response speed, and switching stability). Herein, we reported two novel diphenylamine-based mixed valence (MV) polyamides (S-HPA and P-HPA) with spirobifluorene (2,7-positions) and pyrene (1,6-positions) as bridged fluorescence units, respectively, showing impressive cyclability and fluorescence contrast with rapid switching. Through the formation of an effective electronic coupling between the two nitrogen centers using spirobifluorene/pyrene bridges, we demonstrated that different bridges have significant effects on the thermal and electrooptical characteristics of polyamides. In addition to lower fluorescence quantum yield and glass transition temperature, the S-HPA exhibited superior cyclability (contrast change <3.4%/14% over 500/300 cycles for EC/EFC switching), higher color/fluorescence contrast (64%/304%), and faster switching time (<2.6 s), mainly owing to the shorter conjugated length and more twisted configuration of the spirobifluorene bridge. The design principle of MV polymers with fluorophore bridges proposed here will be a promising way to realize high-performance EC/EFC devices and will also provide new insights into their future development and applications.


The complete mitochondrial genome of Pollicipes mitella (Crustacea, Maxillopoda, Cirripedia): non-monophylies of maxillopoda and crustacea.
The whole mitochondrial genome (14,915 nt) of Pollicipes mitella (Crustacea, Maxillopoda, Cirripedia, Thoracica) was sequenced and characterized. It is the shortest of the 31 completely sequenced crustacean mitochondrial genomes, with the exception of a copepod Tigriopus japonicus (14,628 nt). It consists of the usual 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 relatively short non-coding region (294 nt). The thoracican cirripeds apart from Megabalanus volcano have the same arrangement of protein-coding genes as Limulus polypemus, but there are frequent tRNA gene translocations (at least 8). Some interesting translocation features that may be specific to the thoracican cirriped lineage are as follows: 1) trnK-trnQ lies between the control region and trnI, 2) trnA-trnE lies between trnN and trnS1, 3) trnP lies between ND4L and trnT, and 4) trnY-trnC lies between trnS2 and ND1. In P. mitella there are two trnL genes (L1 and L2) in the typical crustacean positions (ND1-L1-LrRNA and CO1-L2-CO2). The present result is compared and discussed with the other three cirriped mitochondrial genomes from one pedunculate (Pollicipes polymerus) and two sessiles (Tetraclita japonica and M. volcano) published so far. Mitochondrial protein phylogenies reconstructed by the BI and ML algorithms show that the thoracican Cirripedia is monophyletic (BPP 100/BP 100) and associated with Remipedia (BPP 98/BP 35). In addition, Oligostraca, including Ostracoda, Branchiura, and Pentastomida, is a monophyletic group (BPP 99/BP 68), and is basal to all the other examined arthropods. Remipedia + Cirripedia appears as an independent lineage within Arthropoda, apart from Thoracopoda (Malacostraca, Branchiopda, and Cephalocarida). The Thoracopoda is paraphyletic to Hexapoda. The present result suggests that the monophylies of Crustacea and Maxillopoda should be reconsidered.


Identification of human papilloma virus DNA sequence in the hyperplastic epithelium of an oral denture fibroma.
The human papilloma virus (HPV) associated with hyperplastic epithelium in an oral denture fibroma was examined by southern blot hybridization. Extracted DNA was hybridized with full length linear HPV type 2a, 6b, 11, 16, 18, 31 and 33 DNAs as a mixed probe only under low stringent conditions. The hybridized bands digested with Bam HI and Eco RI were approximately 8.8 kbp and 15 kbp, respectively. Thus the lesional HPV DNA was different from HPV types used as probes and was probably integrated into host cell chromosomal DNA judging by the off-size high molecular weight bands. Considering the contaminating mesenchymal region and uninfected epithelial cells as well as the evidently limited homology with probe HPV DNAs, the virus copy number in infected cells was poorly defined. In situ antigen staining signals were widely detected in the hyperplastic epithelial layer.


[Assessment of the cardiotoxicity of recombinant human endostatin using myocardial biochemical markers in cancer patients].
To evaluate the value of the myocardial biochemical markers including creatine kinase MB isoenzyme (CK-MB), cardiac isoform of Tropnin-T (cTnT) and N-termimal pro-brain natriuretic peptide (NT-proBNP) and electrocardiogram (ECG) in monitoring the cardiotoxicity of recombinant human endostatin (rh-endostatin) in cancer patients. Forty cancer patients were divided into two groups and received rh-endostatin in addition to chemotherapy (group A, n=24) or chemotherapy only (Group B, n=24). Serum CK-MB, cTnT levels and plasma NT-proBNP levels were measured and the ECG was recorded in all the patients before and after each of the two therapy cycles. In group A, serum CK-MB, cTnT and plasma NT-proBNP levels were significantly increased after the treatment in comparison with the baseline levels (P<0.05), but such increment was not observed in group B (P>0.05). With comparable baseline levels of CK-MB, cTnT and NT-proBNP before the treatment (P>0.05), patients in group A showed significantly higher levels of the indices than those in group B after each therapy cycle (P<0.05). Increased ECG abnormality were observed after rh-endostatin treatment in Group A (P<0.05) at a rate significantly higher than that of Group B after the second treatment cycle (P<0.05). Rh-endostatin has definite cardiotoxicity, and detection of the myocardial biochemical markers of CK-MB, cTnT and NT-proBNP may help predict the occurrence of cardiotoxicity.


Medicare program; requirements for the Medicare incentive reward program and provider enrollment. Final rule.
This final rule implements various provider enrollment requirements. These include: Expanding the instances in which a felony conviction can serve as a basis for denial or revocation of a provider or supplier's enrollment; if certain criteria are met, enabling us to deny enrollment if the enrolling provider, supplier, or owner thereof had an ownership relationship with a previously enrolled provider or supplier that had a Medicare debt; enabling us to revoke Medicare billing privileges if we determine that the provider or supplier has a pattern or practice of submitting claims that fail to meet Medicare requirements; and limiting the ability of ambulance suppliers to "backbill" for services performed prior to enrollment.


[Interdisciplinary pain assessment in the hospital setting : Merely a door-opener to multimodal pain therapy?]
Chronic pain is characterized by a complex interaction of somatic, mental and social factors. Assessing these factors in patients with chronic pain is vital during the diagnostic work-up and when making a structured treatment plan. Interdisciplinary pain assessment (ISA) is the most promising method to deal with these challenges. This article presents our experience in performing pain assessments in the hospital setting and also illustrates the characteristic features of chronic pain patients undergoing such assessments. This study reviews and evaluates patient data from 2704 ISAs performed at the Interdisciplinary Pain Centre of the Zentralklinik Bad Berka, Germany, between 2008 and 2015. The majority of our ISA patients are severely handicapped and show distinct signs of chronic disease. A large proportion of patients is either unable to work or receiving benefits (invalidity pension or retirement pension). In addition, patients reported long disease durations and high emotional distress. Treatment recommendations were based on the patients' individual clinical presentations and examination results. More than half of the patients required multimodal pain management, while adjustments or therapeutic withdrawal of pain medications, in particular of opioids, were indicated in many patients. Our study shows that ISA enables fast, high-quality diagnostic assessments of chronic pain while taking the biopsychosocial model of pain in particular into account. In addition, ISA is not biased with regard to outcome results and recommends the further treatment that appears best for the individual patient. ISA leads not only to inpatient treatment, but also to treatment in other therapeutic settings and, as such, is not merely a door-opener to multimodal pain therapy.


A hydrophobicity-dependent motif responsible for surface expression of cardiac potassium channel.
The long-QT syndrome (LQTS) is an inherited cardiac disorder associated with syncope and a high risk of sudden death. The molecular basis of type-1 LQTS (LQT1) is a missense or nonsense mutation in KCNQ channels that reduces slowly activating delayed rectifier potassium channel (I(Ks)) resulting in a prolonged action potential. Noticeably, the S2-S3 linker is a highly congregating region of LQT1 mutations. To further explore the mechanism, a KCNQ mutant (L191P) identified in one Chinese pedigree with LQT1 was chosen for this purpose. As Leu-191 is located in the middle of a well-known endoplasmic reticulum (ER) localization signal (RXR) in the intracellular S2-S3 linker, we examined the kinetics and the surface expression of both the KCNQ1 and L191 mutants. Our results showed that the mutation did not affect the channel kinetics, whereas the surface expression increased with increasing hydrophobicity of the middle residue 'X' of the RXR motif. Based on an analysis of fractional fluorescence data using a binomial model, we also found that the percentage of KCNQ1/L191P heteromeric channels expressed at the cell surface were 22.0%, 40.5%, 27.9%, 8.6% and 1.0% of heteromeric channels with 0, 1, 2, 3 and 4 subunits of L191P, respectively, in a transfected ratio of KCNQ1: L191P=1:1. These experiments demonstrated that coexpression of L191P resulted in a trafficking factor alpha<1, causing a trafficking deficiency of heteromeric channels that underlay the dominant-negative effect. This study suggests several trafficking signals coexisting in this region, and expands our understanding of possible dominant-negative mechanisms underlying LQTS.


A Biomechanical Comparison of Proportional Electromyography Control to Biological Torque Control Using a Powered Hip Exoskeleton.
Despite a large increase in robotic exoskeleton research, there are few studies that have examined human performance with different control strategies on the same exoskeleton device. Direct comparison studies are needed to determine how users respond to different types of control. The purpose of this study was to compare user performance using a robotic hip exoskeleton with two different controllers: a controller that targeted a biological hip torque profile and a proportional myoelectric controller. We tested both control approaches on 10 able-bodied subjects using a pneumatically powered hip exoskeleton. The state machine controller targeted a biological hip torque profile. The myoelectric controller used electromyography (EMG) of lower limb muscles to produce a proportional control signal for the hip exoskeleton. Each subject performed two 30-min exoskeleton walking trials (1.0 m/s) using each controller and a 10-min trial with the exoskeleton unpowered. During each trial, we measured subjects' metabolic cost of walking, lower limb EMG profiles, and joint kinematics and kinetics (torques and powers) using a force treadmill and motion capture. Compared to unassisted walking in the exoskeleton, myoelectric control significantly reduced metabolic cost by 13% (p = 0.005) and biological hip torque control reduced metabolic cost by 7% (p = 0.261). Subjects reduced muscle activity relative to the unpowered condition for a greater number of lower limb muscles using myoelectric control compared to the biological hip torque control. More subjects subjectively preferred the myoelectric controller to the biological hip torque control. Myoelectric control had more advantages (metabolic cost and muscle activity reduction) compared to a controller that targeted a biological torque profile for walking with a robotic hip exoskeleton. However, these results were obtained with a single exoskeleton device with specific control configurations while level walking at a single speed. Further testing on different exoskeleton hardware and with more varied experimental protocols, such as testing over multiple types of terrain, is needed to fully elucidate the potential benefits of myoelectric control for exoskeleton technology.


C1QBP negatively regulates the activation of oncoprotein YBX1 in the renal cell carcinoma as revealed by interactomics analysis.
The Y-box-binding protein 1 (YBX1) plays a critical role in tumorigenesis by promoting cell proliferation, overriding cell-cycle check points, and enhancing genomic instability. In this study, the interactome of YBX1 in renal cell carcinoma (RCC) was analyzed by coimmunoprecipitation and mass spectrometry to better understand its function and regulatory mechanism. A total of 129 proteins were identified as potential YBX1 binding partners. The interaction between the complement component 1, q subcomponent binding protein (C1QBP), and YBX1 was further confirmed by immunoprecipitation and Western blotting. Knockdown of C1QBP enhanced the phosphorylation of YBX1and its nuclear translocation, indicating that C1QBP negatively regulated YBX1 activation. The clinical significance of these two proteins was analyzed in the tissues from 52 RCC patients by immunohistochemistry. Expression of YBX1 was markedly elevated in the carcinoma tissues, and its nuclear expression was associated with histological T stage and metastasis. Meanwhile, the level of C1QBP in the carcinoma tissues was significantly lower than that in the adjacent healthy tissues, which was negatively correlated with the nuclear localization of YBX1 in the RCC tissues (P = 0.011). These data suggest that C1QBP is a novel regulator of YBX1, and the expression of C1QBP and the nuclear expression of YBX1 could both be used as independent prognostic makers for cancer progression in the RCC patients. The proteomics data have been deposited to the ProteomeXchange with identifier PXD001493.


Talar morphology of azibiids, strepsirhine-related primates from the Eocene of Algeria: phylogenetic affinities and locomotor adaptation.
The HGL-50 locality, situated on the Glib Zegdou outlier in the Gour Lazib of Algeria (Hammada du Dra), is famous for having yielded several dental remains of primates dating from the late Early to the early Middle Eocene. These primates include Algeripithecus minutus, Azibius trerki and a new species of cf. Azibius (not described yet). Algeripithecus was widely acknowledged to be one of the oldest known anthropoids from Africa. However, very recent discoveries strongly suggest that Algeripithecus is closely related to Azibius and that both taxa are phylogenetically remote from the clade Anthropoidea. Algeripithecus and Azibius make up the family Azibiidae and appear as stem strepsirhines. Here we describe and analyse two ankle bones (tali) found in HGL-50. UM/HGL50-466 is a small left talus, which is appropriate in size to belong to A. trerki, while UM/HGL50-467 is a right talus, which is significantly larger and appropriate in size to belong to the new large species of cf. Azibius. Both tali exhibit a suite of features that resemble conditions primarily found in extinct and extant strepsirhine and adapiform primates; conditions that are consistent with the strepsirhine-like dentition characterizing azibiids. Functionally, these two tali indicate that Azibius species were engaged in a form of active arboreal quadrupedalism with some ability to climb and leap. Azibiids were rather small-bodied primates, approximating the size of some modern dwarf lemurs (Cheirogaleidae) and sportive lemurs (Lepilemuridae) from Madagascar. Given their small body-size and their talar morphology, living cheirogaleid lemurs, which are agile arboreal quadrupeds (with climbing, springing and branch running activities), might appear as good analogues for azibiids in terms of locomotor behaviour.


Risk factors for severe pneumonia in children in south Kerala: a hospital-based case-control study.
A case-control study was undertaken in 400 children under 5 years of age in South Kerala, India, to identify the risk factors for severe pneumonia. Cases were in-patients with severe pneumonia as ascertained by WHO criteria, while controls were out-patients with non-severe acute respiratory infections. Only four from many probable risk factors emerged as being significant, viz. young age, immunization, delayed weaning, and sharing of bedroom. The significant factors on univariate analysis were parental education, environmental pollution, discontinuation of breastfeeding in young infants, malnutrition, hypovitaminosis A, low birth weight, previous history of severe ARI, unresponsiveness to earlier treatment, and use of non-allopathic medicine. Correction of these factors can probably reduce mortality due to ARI.


Unusual cause of recalcitrant epistaxis.
Nosebleeds are among the most familiar presentations to the emergency department as well as otorhinolaryngologic outpatient services. Bleeding from nasal septal branches of the anterior ethmoid artery (AEA) is common and can be effectively controlled endoscopically. However, the bleeding from a pseudoaneurysm involving the nasal septal branches of AEA is extremely rare and can be troublesome to control using endoscopic methods. We report an adult patient presenting with profuse nasal bleeding postroad traffic accident due to the formation of AEA septal branch pseudoaneurysm. The patient required repeated nasal packing, and the diagnosis was revealed using digital subtraction angiography. Since profuse active bleeding precluded endoscopic visualisation, an external approach had to be adopted to ligate the AEA to control the bleeding. We discuss the management options and nuances for this rare cause of the troublesome nasal bleeding.


Injury patients' perceptions of drink-driving: A qualitative assessment of drink-driving behavior in Moshi, Tanzania.
Globally, about 2.3 billion people are current alcohol drinkers, and 283 million have an alcohol use disorder. Alcohol use while driving is a major contributor to road traffic injuries (RTI). We need to understand the culture and perception of drink-driving in this setting to understand why people continue to drink drive and allow policymakers to develop more effective ways to address drink-driving behavior. This study aims to qualitatively determine what injury patients, their families, and community advisory board members in Tanzania believe about drink-driving to help inform policies to address this problem. The semi-structured focus group was designed based on the grounded theory and assessed using thematic analysis. Focus groups participants were a convenience sample of injury patients, their families, and community advisory board (CAB) members. Analysis was iterative throughout the study. All transcripts were coded using a thematic narrative approach. Representative quotes for each theme were then selected based on comparative analysis of coding with input from research team members. A total of ten focus groups were conducted (4 patient, 4 family, and 2 CAB) with a total of 104 participants (37 females and 67 males). The normalization of drinking among drivers has allowed this behavior to become ingrained in the culture. Participants expressed notions that passengers are responsible for their own safety, rather than drivers being responsible for their passengers. Most participants believe it is a citizen's duty to inform the police of suspected drink-driving, however there were differing opinions about how effective informed police officers can be in practice. Focus group discussions between all three population types highlighted major themes of 'drinking is ingrained in boda boda driver culture', 'individuals have a personal responsibility to address drink-driving', and a 'police enforcement on drink-driving is necessary'. Normalization of drink-driving in commercial driver culture creates a dangerous environment for passengers which can be mitigated by education and health promotion. As most passengers already take personal responsibility for their own road traffic safety, they may be likely to make use of safe ride options, if available. While legislation is in place against drink-driving, police officers need to be empowered with appropriate training and funding to enforce them.


NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration.
Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance. The mechanisms of NRIP-regulated muscle contraction depend on NRIP being downstream of Ca(2+) signaling, where it stimulates activation of both 'calcineurin-nuclear factor of activated T-cells, cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting in the induction of mitochondrial activity and the expression of genes encoding the slow class of myosin, and in the regulation of Ca(2+) homeostasis through the internal Ca(2+) stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout mice have a delayed regenerative capacity. The amount of NRIP can be enhanced after muscle injury and is responsible for muscle regeneration, which is associated with the increased expression of myogenin, desmin and embryonic myosin heavy chain during myogenesis, as well as for myotube formation. In conclusion, NRIP is a novel Z-disc protein that is important for skeletal muscle strength and regenerative capacity.


The need for pediatric studies of allergy and asthma medications.
For many years, clinicians have accepted the fact that most medications do not have dosing guidelines for children younger than 12 years of age. Recently, there has been a great effort to correct this deficiency. With the introduction of the 1997 Food and Drug Administration Modernization Act, a provision was established to grant additional market exclusivity to pharmaceutical firms that performed the required studies that would lead to improved labeling of medications for children. This effort has resulted in a significant advance for the management of asthma and allergic disorders in children. Several allergy and asthma medications are now approved for use in children as young as 1 year of age, with studies currently being conducted in younger age groups. In this review, we discuss the background for this effort and the continuing impact it will have on the future management of allergy and asthma in children.


Wide local excision for Merkel cell carcinoma of the lower extremity: A case report.
Primary Merkel cell carcinoma (MCC) is rare and wide local excision is the primary method of treatment. However, no consensus has been reached on the best surgical approach and research is currently limited. The choice of surgical method depends on the experience of the surgeon and the situation of the patient. In the present study, the clinical data of a single case of primary MCC that was treated with wide local excision in June 2019 were retrospectively analyzed and the associated literature was reviewed. The patient underwent complete resection of the tumor, which extended 2 cm from the outer edge of the nodule and reached the subcutaneous fat layer. The wound was closed with a tension-relieving suture. The stitches were removed 15 days following surgery and the wound had healed adequately. No recurrence occurred during 30 months of follow-up. However, further multi-center prospective randomized clinical trials are required for further investigation.


A 10 year survey of acaricide residues in beeswax analysed in Italy.
The aim of this work was to provide an overview of the prevalence and level of acaricides in beeswax used in Italy in the past 10 years by analysing 1319 beeswax samples processed by the certified laboratory of the Italian Bee Research Institute. The proportion of samples positive to at least one active ingredient decreased between 2005 and 2009 (from 69 to 32%) and then increased again between 2009 and 2014 (from 32 to 91%). This trend is in agreement with reports from beekeepers that the use of synthetic acaricides decreased in the second half of the past decade and increased after the beginning of the colony losses phenomenon. The active ingredient with the greatest overall proportion of positive samples was coumaphos (49%), followed by fluvalinate (38%) and chlorphenvinphos (25%). The indicator for amitraz, 2,4-dimethylphenylformamide (DMPF), was detected in a very small proportion of samples (6%), while residues of cymiazole were never found. In more than half of the analysed samples, residues of at least one active ingredient were detected. The mean levels of residues of all the considered active ingredients in the positive samples may represent a source of accumulation in beeswax and pose risks to honey bee health. © 2015 Society of Chemical Industry.


Histological changes during the development of the bovine nuchal ligament.
The histological changes occurring during the development of the bovine nuchal ligament have been observed in sections of formalin-fixed material from 21 animals ranging in age from 110 days of gestation to 10 yr. The elastic fibers which constitute the bulk of the adult ligament were initially few in number. During fetal development, the fibers showed a rapid increase both in number and in their stainability with the usual elastic stains. The average diameter of these elastic fibers increased only slowly until the last uterine month, at which time it began to increase very rapidly. This rapid rate of increase continued through the first 6 postnatal months, after which the rate of increase slowed markedly. However, the fiber diameter continued to rise steadily throughout the period of the study. During the fetal stage of development, the fibroblastic cells of the ligament exhibited unusual nuclear appearances which distinguish them from other fibroblasts. These consisted of marked clumping of the chromatin and an associated nuclear vacuolation or vesiculation. While these changes seem likely to be artefacts of fixation, their temporal correlation with elastin deposition and their demonstration in other tissue cells engaged in elastin production suggest that the factors responsible for these appearances may be related to elastin synthesis.


Visual outcomes in children with neurofibromatosis type 1 and orbitotemporal plexiform neurofibromas.
To describe the visual outcomes and volumetric magnetic resonance imaging (3D MRI) in children with neurofibromatosis type 1 (NF1) and orbitotemporal plexiform neurofibromas. Multicenter retrospective case series. Two institutions with dedicated NF1 clinical research programs queried their established clinical databases for children with orbitotemporal plexiform neurofibromas. Visual acuity, refractive error, ambylopia, and treatment history were abstracted. Extent of orbitotemporal plexiform neurofibroma involvement was assessed clinically and with 3D MRI analysis. Children with optic pathway gliomas or ocular causes of decreased visual acuity (ie, cataracts, glaucoma) other than strabismus or anisometropia were excluded. Twenty-one children met inclusion criteria (median age 8 years, range 0.33-23 years). Orbitotemporal plexiform neurofibroma location was classified as isolated eyelid (n = 6), eyelid and orbit (n = 7), orbit and temporal region (n = 7), or diffuse orbit (n = 1). Three subjects had bilateral orbital involvement. Amblyopia secondary to the orbitotemporal plexiform neurofibroma was present in 13 subjects (62%) and was caused by strabismus (n = 2, 10%), occlusion from ptosis (n = 9, 43%), or anisometropia (n = 9, 43%), or a combination of factors (n = 6, 29%). MRI-derived volumes were measured in 19 subjects (median 41.8 mL, range 2.7-754 mL). All subjects with amblyopia had orbitotemporal plexiform neurofibroma volumes greater than 10 mL. In our series, amblyopia occurs in more than half of NF1 children with orbitotemporal plexiform neurofibromas, most commonly because of ptosis and anisometropia. The 3D MRI analysis allowed for sensitive measurement of orbitotemporal plexiform neurofibroma size, and larger volumes were associated with development of amblyopia.


Autonomy and paternalism in geriatric medicine. The Jewish ethical approach to issues of feeding terminally ill patients, and to cardiopulmonary resuscitation.
Respecting and encouraging autonomy in the elderly is basic to the practice of geriatrics. In this paper, we examine the practice of cardiopulmonary resuscitation (CPR) and "artificial" feeding in a geriatric unit in a general hospital subscribing to jewish orthodox religious principles, in which the sanctity of life is a fundamental ethical guideline. The literature on the administration of food and water in terminal stages of illness, including dementia, still shows division of opinion on the morality of withdrawing nutrition. We uphold the principle that as long as feeding by naso-gastric (N-G) or percutaneous endoscopic gastrostomy (PEG) does not constitute undue danger or arouse serious opposition it should be given, without causing suffering to the patient. This is part of basic care, and the doctor has no mandate to withdraw this. The question of CPR still shows much discrepancy regarding elderly patients' wishes, and doctors' opinions about its worthwhileness, although up to 10 percent survive. Our geriatric patients rarely discuss the subject, but it is openly ventilated with families who ask about it, who are then involved in the decision-making, and the decision about CPR or "do-not-resuscitate" (DNR) is based on clinical and prognostic considerations.


Comparison of hygiene levels in metal-ceramic and stratified zirconia in prosthetic rehabilitation on teeth and implants: a retrospective clinical study of a three-year follow-up.
The aim of this retrospective clinical study was to evaluate and compare oral hygiene levels in patients subjected to fixed metal-ceramic or stratified zirconia prostheses, either on teeth or on dental implants. Twenty patients, including 10 with metal-ceramic prostheses and 10 with stratified zirconia, were engaged for the study. Considering the prosthesis positioning phase as zero time, all patients were examined twice a year for a follow-up period of 3 years. During each session, to assess oral cavity state of health, both the Plaque Index (IP) and the Bleeding Index (BOP) were recorded. All patients were instructed in home hygiene maintenance and subjected to professional oral hygiene sessions customized according to prothesis type (on natural teeth or dental implants) and materials (metal ceramic or stratified zirconia). Statistically significant evidence was found in IP values, with an increase in the initial stages in zirconia prostheses and in the final stages in metal-ceramic ones. BOP levels showed a reduction during the follow-up period, but no statistically significant differences were found between examined groups. An adequate patient education in hygiene maintenance associated with professional oral hygiene sessions with special tools could positively affect fixed prostheses' maintenance, both on natural teeth and on dental implants.


Clinical evaluation of a polyacid-modified resin composite (Dyract) in class III cavities: three-year results.
This study evaluated the three-year clinical performance of a polyacid-modified resin composite material, Dyract (DeTrey/Dentsply, Konstanz, Germany), in Class III cavities. Sixty-two Class III cavities in 30 patients were restored with Dyract. Restorations were clinically evaluated at baseline, one-, two- and three-year recalls according to the modified Ryge criteria by two experienced, calibrated examiners. After three years, the retention rate was 96.7%. At the one-year interval, one restoration had to be replaced due to sensitivity. At the two-year recall, one restoration, with a caries lesion adjacent to its margin, was clinically unacceptable and had to be replaced. Except for these two restorations, all other restorations were clinically acceptable in regard to color match, marginal discoloration, wear or loss of anatomical form, caries, marginal adaptation and surface texture after three years. At the end of three years, marginal discoloration was statistically significant (p=0.017) but did not require replacement of any of the restorations. Dyract exhibited significant marginal discoloration after three-year clinical performance in Class III cavities.


Successful use of tocilizumab in polymyalgic onset biopsy positive GCA with large vessel involvement.
A 63-year-old female presented with a 12-week history of worsening proximal pain and stiffness. She was diagnosed with polymyalgia rheumatica and started on corticosteroids. The authors were unable to wean-off her steroid treatment, despite trying various steroid sparing agents on different occasions with no benefit. In August 2010, she was diagnosed with giant cell arteritis with a temporal artery biopsy and ultrasound of the temporal and axillary arteries. An fluorine-18-deoxyglucose positron emission tomography CT showed increased uptake in the aorta and major vessels, in keeping with widespread large vessel involvement. Due to the disease severity, the failure of previous disease-modifying agents and the development of steroid related sideeffects, the authors decided to treat her with intravenous tocilizumab (TCZ;an interleukin 6 blocker). After her first infusion, the patient reported excellent response with normalisation of her inflammatory markers. Prednisolone reduced from 20 mg to 3.5 mg /day after five infusions of TCZ (8 mg/kg).


PREVALENCE OF HEPATITIS C IN DIABETIC PATIENTS: A PROSPECTIVE STUDY.
There is a strong evidence of the relationship between diabetes and hepatitis C however, there are certain gaps in the literature. Therefore, this study was carried out to determine the prevalence of hepatitis C in diabetic patients and risk factors associated with it, to evaluate the presence of possible relationship between hepatitis C and diabetes. Serological testing for anti HCV antibody was carried out on a sample of 100 diabetic patients visiting the diabetic clinic Nishtar Medical College and Hospital Multan. An anti HCV antibody test was carried out on HCV ELISA 3.0 (third generation) kit, locally purchased. Data about demographic information and history of risk factors for HCV was collected from diabetic patients using a structured questionnaire as an experimental tool, after taking informed consent. Data of about 100 non diabetic subjects (volunteer blood donors) was taken from the blood bank of that hospital. Prevalence rate of HCV infection among diabetic patients was recorded 19% and in the control group (non-diabetics) was 3%. Prevalence of HCV infection is higher in type 2 diabetic patients as compared to type 1 diabetic patients (84% vs. 16%). Diabetic patients between age group 46-55 years of age has high prevalence rates (47%) as compared to healthy individuals. Female diabetic patients have higher seropositivity (74%) as compared to male diabetic patients (26%). High prevalence of HCV infection has been reported among diabetic patients with duration of disease = 11 years (47%). Most of the patients were married (95%) and from urban locality (89%) and almost all were poor (99%). HCV positive diabetic patients have also history of blood transfusion (16%), hospital admissions (84%), major surgical procedure (63%), family history of hepatitis C (16%), razor sharing among males (16%) and comb sharing (79%). There was not any I/V drug addict (or history of I/V drug addiction), and tattooing, nose/ear piercing from contaminated needle and toothbrush sharing have not been seen among the participants of research.The results showed that in the present study the prevalence of HCV infection is six times higher in diabetic patients as compared to non-diabetic subjects (control group).


Rodent, large animal and non-human primate models of spinal cord injury.
In this narrative review we aimed to assess the usefulness of the different animal models in identifying injury mechanisms and developing therapies for humans suffering from spinal cord injury (SCI). Results obtained from rodent studies are useful but, due to the anatomical, molecular and functional differences, confirmation of these findings in large animals or non-human primates may lead to basic discoveries that cannot be made in rodent models and that are more useful for developing treatment strategies in humans. SCI in dogs can be considered as intermediate between rodent models and human clinical trials, but the primate models could help to develop appropriate methods that might be more relevant to humans. Ideally, an animal model should meet the requirements of availability and repeatability as well as reproduce the anatomical features and the clinical pathological changing process of SCI. An animal model that completely simulates SCI in humans does not exist. The different experimental models of SCI have advantages and disadvantages for investigating the different aspects of lesion development, recovery mechanisms and potential therapeutic interventions. The potential advantages of non-human primate models include genetic similarities, similar caliber/length of the spinal cord as well as biological and physiological responses to injury which are more similar to humans. Among the potential disadvantages, high operating costs, infrastructural requirements and ethical concerns should be considered. The translation from experimental repair strategies to clinical applications needs to be investigated in future carefully designed studies.


Sperm-associated antigens as targets for cancer immunotherapy: expression pattern and humoral immune response in cancer patients.
The identification of novel cancer-related and immunogenic proteins is still a challenge to be faced to improve antigen-specific tumor immunotherapy. The category of so-called cancer-testis (CT) antigens is one of the most perspective groups of proteins for anticancer immune response activation as normally they are expressed in immunoprivileged tissues and are immunogenic if aberrantly generated in tumors. The heterogeneous group of proteins called sperm-associated antigens (SPAG) might encompass novel CT antigens owing to their common expression in male germ cells, their ability to elicit immune response underlying infertility, and lately proposed oncogenic properties. We carried out a comprehensive analysis of the expression pattern in various normal and cancerous tissues and assessed the frequency of spontaneous humoral immune response against members of the SPAG group in cancer patients using phage-displayed antigen microarrays. Our results show that out of 15 analyzed SPAG genes only SPAG1, SPAG6, SPAG8, SPAG15, and SPAG17 are predominantly expressed in testis, whereas the others are ubiquitously expressed with only a testis-associated alternative splice variant of SPAG16. mRNA expression of SPAG1, SPAG6, and alternative splice variants of SPAG8, SPAG16, and SPAG17 was elevated in various tumors with frequencies ranging from approximately 10% to 70%. The upregulation of SPAG6 in lung and breast cancer was confirmed by immunohistochemical analysis of tumor and normal tissue microarrays. Cancer-associated spontaneous humoral immune response was detected against SPAG1, SPAG6, SPAG8, and a novel testis-specific splice variant of SPAG17 and ascribe these as novel CT antigens that potentially are applicable as immunotherapeutic targets and serologic biomarkers.


Comparison of three immunoassays for diagnosing sensitization to latex in children with spina bifida.
As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1-3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4-9), healthcare professionals (10-12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.


How to design potent and selective DYRK1B inhibitors? Molecular modeling study.
DYRK1B protein kinase is an emerging anticancer target due to its overexpression in a variety of cancers and its role in cancer chemoresistance through maintaining cancer cells in the G0 (quiescent) state. Consequently, there is a growing interest in the development of potent and selective DYRK1B inhibitors for anticancer therapy. One of the major off-targets is another protein kinase, GSK3β, which phosphorylates an important regulator of cell cycle progression on the same residue as DYRK1B and is involved in multiple signaling pathways. In the current work, we performed a detailed comparative structural analysis of DYRK1B and GSK3β ATP-binding sites and identified key regions responsible for selectivity. As the crystal structure of DYRK1B has never been reported, we built and optimized a homology model by comparative modeling and metadynamics simulations. Calculation of interaction energies between docked ligands in the ATP-binding sites of both kinases allowed us to pinpoint key residues responsible for potency and selectivity. Specifically, the role of the gatekeeper residues in DYRK1B and GSK3β is discussed in detail, and two other residues are identified as key to selectivity of DYRK1B inhibition versus GSK3β. The analysis presented in this work was used to support the design of potent and selective azaindole-quinoline-based DYRK1B inhibitors and can facilitate development of more selective inhibitors for DYRK kinases.


Topology optimization for three-dimensional electromagnetic waves using an edge element-based finite-element method.
This paper develops a topology optimization procedure for three-dimensional electromagnetic waves with an edge element-based finite-element method. In contrast to the two-dimensional case, three-dimensional electromagnetic waves must include an additional divergence-free condition for the field variables. The edge element-based finite-element method is used to both discretize the wave equations and enforce the divergence-free condition. For wave propagation described in terms of the magnetic field in the widely used class of non-magnetic materials, the divergence-free condition is imposed on the magnetic field. This naturally leads to a nodal topology optimization method. When wave propagation is described using the electric field, the divergence-free condition must be imposed on the electric displacement. In this case, the material in the design domain is assumed to be piecewise homogeneous to impose the divergence-free condition on the electric field. This results in an element-wise topology optimization algorithm. The topology optimization problems are regularized using a Helmholtz filter and a threshold projection method and are analysed using a continuous adjoint method. In order to ensure the applicability of the filter in the element-wise topology optimization version, a regularization method is presented to project the nodal into an element-wise physical density variable.


Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.
Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream.


Palladium-catalyzed oxidative carbonylation of N-aryl enamino esters with CO and alcohols: synthesis of N-aryl aminomethylenemalonates.
A novel palladium-catalyzed regioselective oxidative carbonylation of tri-substituted alkenes with CO and alcohols for the synthesis of α,β-unsaturated esters has been developed. Experimental studies and DFT calculations suggested that the reaction proceeded through alkoxylation of the palladium(ii) catalyst, CO and C[double bond, length as m-dash]C double bond migratory insertion, β-(N)H elimination and tautomerization cascade steps. The reaction tolerates a wide range of groups and produces valuable aminomethylenemalonates in high yields.


[Morphological variability and population structure of the cestode Proteocephalus longicollis (Zeder, 1800) in aquaculture].
Morphological variability of the cestode Proteocephalus longicollis (Zeder, 1800) from Coregonus peled (Gmelin, 1789) was studied in natural host population from the Pelyadka River and in aquaculture from the Kuchak Lake. Variability of morphometric characters of the parasite is recorded. Sample from the Kuchak Lake differs from the sample collected in the Pelyadka River by a greater number of testes, larger size of worms, smaller size of cirrus bursa and smaller ratio of the cirrus bursa length and the width of proglottid.


Tensile Bond Strength and Marginal Integrity of a Self-adhering and a Self-etch Adhesive Flowable Composite after Artificial Thermomechanical Aging.
This study aims to compare the self-etch adhesive (SEA) and self-adhesive flowable composite (SAF) concerning tensile bond strength (TBS) and marginal integrity by microleakage (µ LK) test in deciduous molars after artificial thermomechanical aging. 120 extracted primary molars were collected. Sixty teeth were mounted for testing TBS. Teeth were restored using SAF (n = 30) and SEA-conventional flowable (CF) composite (n = 30) and subjected to artificial thermal aging. Half the teeth (n = 15) from each material were subjected to mechanical loading (SEA-TBS-L and SAF-TBS-L). The specimens with no-load (NL) served as control (SEA-TBS-NL and SAF-TBS-NL). Class V cavity prepared and restored with SAF (n = 30) and SEA-CF (n = 30) to test µ LK after thermal aging. The subgroups were as same as the TBS based on with or without mechanical loading (SEA-µ LK-L, SEA-µ LK-NL, SAF-µ LK-L, SAF-µ LK-L; n = 15 each). µ LK was determined by employing the dye immersion technique. Concerning TBS, there is a significant difference between SEA and SAF with load or no load. Concerning µ LK, there is a significant difference between the materials under loading and no difference was found when not mechanically loaded. Also, concerning both TBS and µ LK, a significant difference was observed between the load and no-load subgroups within each material. SAF exhibited higher TBS than the SEA. Mechanical loading not only adversely affected the TBS but also increased the µLK of the compared materials. Restoring the primary teeth with SAF not only shortens the laborious operatory time but also yields good clinical serviceability with the good bond strength and minimal µ LK, thus preventing premature loss of teeth and consequential malocclusion. Kamatchi M, Ajay R, Gawthaman M, et al. Tensile Bond Strength and Marginal Integrity of a Self-adhering and a Self-etch Adhesive Flowable Composite after Artificial Thermomechanical Aging. Int J Clin Pediatr Dent 2022;15(2):204-209.


ADH1B: From alcoholism, natural selection, and cancer to the human phenome.
The ADH1B (Alcohol Dehydrogenase 1B (class I), Beta Polypeptide) gene and its best-known functional alleles, Arg48His (rs1229984, ADH1B*2) and Arg370Cys (rs2066702, ADH1B*3), have been investigated in relation to many phenotypic traits; most frequently including alcohol metabolism and alcohol drinking behaviors, but also human evolution, liver function, cancer, and, recently, the comprehensive human phenome. To understand ADH1B functions and consequences, we provide here a bioinformatic analysis of its gene regulation and molecular functions, literature review of studies focused on this gene, and a discussion regarding future research perspectives. Certain ADH1B alleles have large effects on alcohol metabolism, and this relationship particularly encourages further investigations in relation to alcoholism and alcohol-associated cancer to understand better the mechanisms by which alcohol metabolism contributes to alcohol abuse and carcinogenesis. We also observed that ADH1B has complex mechanisms that regulate its expression across multiple human tissues, and these may be involved in cardiac and metabolic traits. Evolutionary data strongly suggest that the selection signatures at the ADH1B locus are primarily related to effects other than those on alcohol metabolism. This is also supported by the involvement of ADH1B in multiple molecular pathways and by the findings of our recent phenome-wide association study. Accordingly, future studies should also investigate other functions of ADH1B potentially relevant for the human phenome. © 2017 Wiley Periodicals, Inc.


Substrate Recognition and Modification by a Pathogen-Associated Aminoglycoside Resistance 16S rRNA Methyltransferase.
The pathogen-associated 16S rRNA methyltransferase NpmA catalyzes m1A1408 modification to block the action of structurally diverse aminoglycoside antibiotics. Here, we describe the development of a fluorescence polarization binding assay and its use, together with complementary functional assays, to dissect the mechanism of NpmA substrate recognition. These studies reveal that electrostatic interactions made by the NpmA β2/3 linker collectively are critical for docking of NpmA on a conserved 16S rRNA tertiary surface. In contrast, other NpmA regions (β5/β6 and β6/β7 linkers) contain several residues critical for optimal positioning of A1408 but are largely dispensable for 30S binding. Our data support a model for NpmA action in which 30S binding and adoption of a catalytically competent state are distinct: docking on 16S rRNA via the β2/3 linker necessarily precedes functionally critical 30S substrate-driven conformational changes elsewhere in NpmA. This model is also consistent with catalysis being completely positional in nature, as the most significant effects on activity arise from changes that impact binding or stabilization of the flipped A1408 conformation. Our results provide a molecular framework for aminoglycoside resistance methyltransferase action that may serve as a functional paradigm for related enzymes and a starting point for development of inhibitors of these resistance determinants.


CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes.
Terpenoid indole alkaloid (TIA) biosynthesis in Catharanthus roseus is a complex and highly regulated process. Understanding the biochemistry and regulation of the TIA pathway is of particular interest as it may allow the engineering of plants to accumulate higher levels of pharmaceutically important alkaloids. Toward this end, we generated a transgenic C. roseus hairy root line that overexpresses the CrBPF1 transcriptional activator under the control of a β-estradiol inducible promoter. CrBPF1 is a MYB-like protein that was previously postulated to help regulate the expression of the TIA biosynthetic gene STR. However, the role of CrBPF1 in regulation of the TIA and related pathways had not been previously characterized. In this study, transcriptional profiling revealed that overexpression of CrBPF1 results in increased transcript levels for genes from both the indole and terpenoid biosynthetic pathways that provide precursors for TIA biosynthesis, as well as for genes in the TIA biosynthetic pathway. In addition, overexpression of CrBPF1 causes increases in the transcript levels for 11 out of 13 genes postulated to act as transcriptional regulators of genes from the TIA and TIA feeder pathways. Interestingly, overexpression of CrBPF1 causes increased transcript levels for both TIA transcriptional activators and repressors. Despite the fact that CrBPF1 overexpression affects transcript levels of a large percentage of TIA biosynthetic and regulatory genes, CrBPF1 overexpression has only very modest effects on the levels of the TIA metabolites analyzed. This finding may be due, at least in part, to the up-regulation of both transcriptional activators and repressors in response to CrBPF1 overexpression, suggesting that CrBPF1 may serve as a "fine-tune" regulator for TIA biosynthesis, acting to help regulate the timing and amplitude of TIA gene expression.


NMDA receptor overstimulation triggers a prolonged wave of immediate early gene expression: relationship to excitotoxicity.
Exposure of the rodent striatum to quinolinic acid (QA, N-methyl-D-aspartate receptor agonist) induces immediate early gene (IEG; c-fos, c-jun, jun-B, zif/268) expression that may extend 12-24 h after injection. In order to determine the specificity of the prolonged IEG response to the QA injection, the temporal pattern of c-fos mRNA expression was examined during the first 4 h after administration of saline or QA (40 micrograms). As early as 30 min after intrastriatal injection, both saline and QA increased c-fos mRNA levels. In the saline group, this increase in IEG expression was only transient and returned to baseline by 1 h. In contrast, c-fos mRNA levels within QA-injected animals continued to rise significantly at 1 and 4 h. In a second experiment, rats received 4 ng to 40-micrograms injections of QA followed by sacrifice at 6 h to determine if increasing QA doses caused the appearance of the prolonged IEG response phase. The prolonged IEG response was evident at 6 h only in animal groups that received higher dose ranges (4-40 micrograms) of QA. A final experiment was undertaken to determine if blockage of NMDA receptor stimulation would also inhibit the prolonged IEG response at 6 h in relationship to neuronal sparing evidenced at 24 h post-QA injection. The NMDA receptor antagonist, MK-801, blocked the prolonged IEG response at 6 h following QA (40 micrograms) injection while also preventing striatal neuropeptide mRNA decline by 24 h. Delaying the MK-801 administration for 1-2 h post-QA injection revealed that the intensity of the prolonged IEG mRNA response may be predictive of neuronal demise within the QA lesion site. These results suggest that prolonged IEG expression is associated with QA excitotoxicity of the rodent striatum and subsequent neuronal degeneration.


Surgical outcome of volar plate arthroplasty of the proximal interphalangeal joint using the Mitek micro GII suture anchor.
The mechanism of injury in dorsal dislocation is usually a hyperextensive stress simultaneous with some degree of longitudinal compression. Operative treatment is indicated for those unstable and reduction is not achieved. We report the surgical outcome of volar plate arthroplasty of the proximal interphalangeal (PIP) joint using the Mitek Micro GII suture anchor. We reviewed the medical records of 20 patients with acute or chronic dorsal dislocation or subluxation of the PIP joint who were managed using the Mitek Micro GII suture anchor over the past 5 years by the same surgeon (J.T.S.). Fourteen patients had acute injuries (<4 weeks before surgery) and six patients had chronic injuries (average interval of 4.1 week from injury to surgery; range, 1-8 weeks). The patients had persistent pain and loss of range of motion after trauma, and the reductions were still unstable. All patients were evaluated an average of 25 months postoperatively (range, 12-30 months). The average arc of motion of the PIP joints of the fingers was 82 degrees . There were no obvious perioperative complications, and no patient reported pain at rest or with activity. Volar plate arthroplasty using the Mitek Micro GII suture anchor is an effective treatment choice for acute or chronic PIP joint dorsal dislocation or subluxation.


Coagulation Assay and Stroke Severity upon Admission of Patients with Cardioembolic Cerebral Infarction during Direct Oral Anticoagulant Use.
Although the severity of acute cerebral infarction varies in patients receiving direct oral anticoagulants (DOACs), no practical method to predict the severity has been established. We analyzed retrospectively the relationship between cardioembolic cerebral infarction severity and coagulation indicators in patients treated with DOACs. We assessed the anticoagulation effect of DOACs using the activated partial thromboplastin time (APTT), prothrombin time (PT), and prothrombin time international standardized ratio (PT-INR) in 71 patients with cardioembolic cerebral infarction admitted to our hospital between January 2015 and December 2019. The participants were divided into a prolongation group (prolonged APTT for oral thrombin inhibitors or prolonged PT for oral factor Xa inhibitors, n =37) and a normal group (no prolongation of coagulation markers, n =34). Of the 71 patients, 21 (30%) and 50 (70%) were using oral thrombin and oral factor Xa inhibitors, respectively. PT, PT-INR, and APTT were significantly higher in the prolongation group (PT: 17.4 ± 5.1 vs. 12.8 ± 1.4 s, P < 0.001; PT-INR: 1.5 ± 0.5 vs. 1.1 ± 0.1, P < 0.001; APTT: 44.8 ± 26.4 vs. 30.4 ± 4.1 s, P = 0.003). The median National Institutes of Health Stroke Scale (NIHSS) score on admission and the prevalence of large vessel occlusion were significantly lower in the prolongation group (NIHSS: 2.0 vs. 9.5, P = 0.007; large vessel occlusion: 27% vs. 53%, P = 0.031). The prevalence of large vessel occlusion was low and stroke severity was mild in patients undergoing DOAC therapy with prolongation of coagulation assay markers upon onset of cardioembolic cerebral infarction.


A 16-year-old with ST elevation myocardial infarction: case report and review of the literature.
Chest pain in young adults presents a unique diagnostic challenge, placing young patients at an increased risk to be misdiagnosed, as this patient population typically does not demonstrate the traditional risk factors associated with cardiovascular disease. This study details the case of a 16-year-old male who presented with new-onset chest pain and ST elevation on electrocardiogram. His history was unremarkable for known cardiac risk factors, but laboratory evaluation demonstrated markedly elevated troponins and electrocardiographic findings confirmed ST-segment elevation myocardial infarction. Coronary angiography demonstrated 100% occlusion of the left anterior descending artery, which was managed with percutaneous transluminal coronary angioplasty, thrombectomy, and bare-metal stenting. The patient had an uneventful recovery. This study examines the major causes of ST elevation myocardial infarction in young adults and reviews the major differences between younger and older myocardial infarction populations with emphasis on risk factor profile, pathophysiological mechanisms, clinical presentation, angiographic findings, and prognosis. This review highlights the need for consideration of a wide differential in younger subsets of the population presenting with chest pain and ST elevation. The implementation of current adult management protocols and guidelines for ST elevation myocardial infarction should not be overlooked due to age. Given the potential for premature death and long-term disability with resulting individual and societal consequences, it is crucial to understand the importance of correct diagnostic evaluation in this clinical scenario.


Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade.
We have recently identified signal transducer and activator of transcription 5 (Stat5) as a critical survival factor for prostate cancer cells. We now report that activation of Stat5 is associated with high histological grade of human prostate cancer. Specifically, immunohistochemical analysis demonstrated a strong positive correlation with activation of Stat5 and high Gleason score in 114 human prostate cancers. To investigate the mechanisms underlying constitutive activation of Stat5 in prostate cancer, a dominant-negative mutant of Janus kinase 2 (Jak2) was delivered by adenovirus to CWR22Rv cells. Dominant-negative-Jak2 effectively blocked the activation of Stat5 whereas wild-type Jak2 enhanced activation, indicating that Jak2 is the main kinase that phosphorylates Stat5 in human prostate cancer cells. A ligand-induced mechanism for activation of Stat5 in prostate cancer was suggested by the ability of prolactin (Prl) to stimulate activation of both Jak2 and Stat5 in CWR22Rv human prostate cancer cells and in CWR22Rv xenograft tumors. In addition, Prl restored constitutive activation of Stat5 in five of six human prostate cancer specimens in ex vivo long-term organ cultures. Finally, Prl protein was locally expressed in the epithelium of 54% of 80 human prostate cancer specimens with positive correlation with high Gleason scores and activation of Stat5. In conclusion, our data indicate that increased activation of Stat5 was associated with more biologically aggressive behavior of prostate cancer. The results further suggest that Jak2 is the principal Stat5 tyrosine kinase in human prostate cancer, possibly activated by autocrine/paracrine Prl.


Measurement of fluorescence using digital integration of video images.
The authors describe a system for the quantitation of fluorescence light output by individual cells using the signal obtained from a silicon intensifier target video camera. The video image is digitized to 4 bits (16 levels), and a 512 X 512 matrix is constructed and stored in 128K of video memory. Areas to be measured are user-specified by means of a light pen entry system. Recorded intensities are integrated under microprocessor control to provide a measure of total fluorescence in the selected areas. The distribution of light intensities per pixel over the 16-level gray scale as well as morphometric data are also obtainable. Linear response to transmission and fluorescence standards was verified. Reproducibility of the system was evaluated using fluorescent beads and glutaraldehyde-fixed chick red blood cells, which gave coefficients of variation comparable to those obtainable from other systems. Measurements of DNA per nucleus of human diploid fibroblasts using Hoechst dye 33258 yielded the two sharp peaks corresponding to the 2C and 4C values of DNA expected from such cells. We conclude that digital video measurement of fluorescence provides meaningful data and has considerable promise as a sensitive tool for the quantitation of fluorescence at the cellular level.


Psychometric properties of the Portuguese version of the occupational fatigue exhaustion/recovery (OFER) scale among industrial shift workers.
Reliable and valid instruments are essential for understanding fatigue in occupational settings. This study analyzed the psychometric properties of the Portuguese version of the Occupational Fatigue Exhaustion/Recovery (OFER). A cross-sectional study was conducted with 260 workers (M = 46.52 ± 13.16 years) from a textile industry, exposed to shift work. Convergent and discriminant validity, internal consistency reliability and exploratory and confirmatory factor analysis were performed. Results showed an adequate fit to data (χ2 (84) = 209,102, CFI = 0.936, GFI = 0.902, RMSEA = 0.076 CI90% (0.063-0.089)), yielding a 13-item, three factor structure. Two items were removed due to low factor loading. The OFER presented an adequate internal consistency, with the subscales presenting good reliability values (Chronic Fatigue (α = 0.81), Acute Fatigue (α = 0.84) and Recovery between Shifts (α = 0.77)). Findings suggest that the Portuguese version of OFER can be a useful tool to assess occupational fatigue of shift workers and prevent work related injuries.


C-reactive Protein is a Useful Marker for Early Prediction of Anastomotic Leakage after Esophageal Reconstruction.
Esophageal anastomotic leakage is one of the most fatal complications after esophagectomy and increases the hospitalization length. We aimed to identify a convenient clinical marker of anastomotic leakage in the early postoperative period. In total, 108 patients who underwent esophagectomy were retrospectively screened, and 96 were used to validate the overall results. All 108 patients underwent physical examinations and determination of their white blood cell count, C-reactive protein level, platelet count, fibrinogen level, fibrin degradation product level, and antithrombin III level until postoperative day 6. Anastomotic leakage occurred in 21 of the 108 patients (median detection, 8 days). The C-reactive protein level on postoperative day 3 and fibrinogen level on postoperative day 4 in the leakage group were significantly higher than those in the nonleakage group. Receiver operating characteristic curves for detection of anastomotic leakage were constructed; the cutoff value of C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the 96 patients in the validation group. There was a significant difference between the leakage and nonleakage groups when the C-reactive protein threshold on postoperative day 3 was set at 8.62 mg/dL. However, there was no difference between the groups when the fibrinogen threshold on postoperative day 4 was set at 712 mg/dL. The C-reactive protein level on postoperative day 3 is a valuable predictor of anastomotic leakage after esophagectomy and might allow for earlier management of this complication.


Effects of tumor necrosis factor-α polymorphism on the brain structural changes of the patients with major depressive disorder.
Single Nucleotide Polymorphic (SNP) variations of proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) have been reported to be closely associated with the major depressive disorder (MDD). However, it is unclear if proinflammatory genetic burden adversely affects the regional gray matter volume in patients with MDD. The aim of this study was to test whether rs1799724, an SNP of TNF-α, contributes to the neuroanatomical changes in MDD. In this cross-sectional study, a total of 144 MDD patients and 111 healthy controls (HC) well matched for age, sex and education were recruited from Shanghai Mental Health Center. Voxel-based morphometry (VBM) followed by graph theory based structural covariance analysis was applied to locate diagnosis x genotype interactions. Irrespective of diagnosis, individuals with the high-risk genotype (T-carriers) had reduced volume in left angular gyrus (main effect of genotype). Diagnosis x genotype interaction was exclusively localized to the visual cortex (right superior occipital gyrus). The same region also showed reduced volume in patients with MDD than HC (main effect of diagnosis), with this effect being most pronounced in patients carrying the high-risk genotype. However, neither global nor regional network of structural covariance was found to have group difference. In conclusion, a genetic variation which can increase TNF-α expression selectively affects the anatomy of the visual cortex among the depressed subjects, with no effect on the topographical organization of multiple cortical regions. This supports the notion that anatomical changes in depression are in part influenced by the genetic determinants of inflammatory activity.


DIAGNOdent--an adjunctive diagnostic method for caries diagnosis in epidemiology.
The DIAGNOdent system is intended as an aid to caries detection and has undergone extensive investigation in experimental and clinical studies. Its applicability for epidemiological purposes has yet to be evaluated. The Objective of the present study was to evaluate the DIAGNOdent system under field conditions. The subjects comprised a sub-sample from an on-going epidemiological study. PARTICIPANTS AND CLINICAL SETTING: In 39 individuals, 97 sites were visually identified as possibly carious: 42 occlusal, 13 lingual, 19 buccal and 23 approximal sites. Three DIAGNOdent measurements were taken at each site under varying conditions: (1) naturally wet, (2) dried, and (3) polished and dried surfaces. Three sets of measurements were obtained and compared by intra-class correlation and paired sample t-tests. All correlation coefficients were > 0.9. There was a systematic difference between mean scores from naturally wet sites (without cleaning) and from either dried, or polished and dried sites. The difference was marginal and did not impact on the threshold for recording sites as carious. In two subjects, high unexpected values were recorded on sound sites prior to actual measurements, i.e. during establishment of a standard value for a sound site. The overall findings were not affected by these values, as they were consistently high in all three measurements. The DIAGNOdent system performed satisfactorily under different measurement conditions. The present study indicates that the DIAGNOdent system would be applicable in field studies, provided consistent study conditions are maintained and unexpected values are interpreted with caution.


The effect of Behçet's disease on sexual function and psychiatric status of premenopausal women.
Little is known about the relationship between Behçet's disease (BD) and female sexual dysfunction (FSD). The aims were to evaluate the prevalence of FSD in premenopausal BD patients and to compare hormonal and psychiatric conditions to healthy subjects. A total of 71 married women with BD and 63 healthy married women between 18 and 44 years old were enrolled into the study. After evaluating detailed history and physical examination, serum steroid hormone levels were measured. Presence of genital ulcerations in physical examination and any medical treatment were recorded in patients. All subjects were asked to complete the Female Sexual Function Index (FSFI) for sexual status and Beck Depression Inventory (BDI) for psychiatric assessment. FSFI and BDI scores and serum sex steroid hormone levels were measured in women with BD and healthy controls. The mean BDI score of patients was significantly greater than that for controls (P = 0.001), and there was a statistically significant difference between BDI scores (Pearson chi2 = 19.109, P = 0.001). FSD was found in 34 patients with BD (47.9%) and in 11 controls (17.5%). A statistically significant difference was found between the two groups (Pearson chi2 = 13.855, P = 0.001). While the most common sexual problem in the patients with BD was diminished arousal (n = 49, 69.0%), diminished desire was found in 32 patients (45.1%) and lubrication problems in 36 patients (50.7%). There was a statistically significant negative correlation between BDI and FSFI score in BD patients. On the contrary, there was no relationship between FSFI and presence of genital ulcerations. FSD is more common in BD patients than in healthy subjects. We conclude that depressive mood according to the BDI scale correlates with the sexual status of BD patients, and this may be because of the depressive effect of BD as a chronic disease.


A non-adiabatic dynamics study of octatetraene: the radiationless conversion from S2 to S1.
Simulation of the excited state dynamics of all-trans-1,3,5,7-octatetraene has been performed to investigate the ultrafast radiationless S2 → S1 internal conversion process. Multireference configuration interaction with single excitation method has been employed to optimize the equilibrium structure of the excited states, as well as the S2/S1 conical intersection, and to investigate the non-adiabatic molecular dynamics of the S2/S1 state transition. At the conical intersection, the molecule is found to be distorted from the original planar trans structure to a nearly perpendicular conformation around C3-C4 bond, with the torsion angle being about 107°. Such structural change can result in mutual approaching of states S2 and S1 in energy, and drastically increase the nonadiabatic coupling between the two states by destroying the inter-state symmetry prohibition in the electronic wavefunctions. Surface-hopping molecular dynamics simulations are performed to describe the non-adiabatic process. Upon the Franck-Condon excitation to the S2 state, the molecule quickly twists its C3-C4 bond and approaches the conical intersection region, where it can undergo efficient internal conversion to S1. The decay time constant (τ) of S2 state is estimated to be around 251 fs by fitting the occupation number of average fraction of trajectories using an exponential damping function. This value is reasonably consistent with previous experimental measurements of around 300-400 fs.


Whistleblowing: a very unpleasant avocation.
This article presents a first-person account of the events surrounding the investigation and sanctioning of Stephen E. Breuning for scientific fraud. The adverse consequences to the whistleblower in this case are also discussed in detail.


Do holes in the T-cell repertoire have a center-surround regulatory structure? A rationale for the bifurcation of the Th1 and Th2 pathways of differentiation.
Regulatory strategies controlling the balance of Th1 versus Th2 T-helper cell responses have been a long-standing mystery with important consequences for immunological disease. A novel model is presented to explain the comparative differentiation of Th1 and Th2 T cells as part of a mechanism to ensure self-tolerance. This model is based on the assumption that thymic interactions of T cell antigen receptors with self major histocompatibility complex ligands may vary in efficacy. By this model, fully agonistic major histocompatibility complex ligands elicit apoptosis during thymic selection to generate 'holes' in the repertoire. Conversely, major histocompatibility complex ligands having some degree of partial efficacy (i.e. a mixed agonist/antagonist) may promote Th2 differentiation whereas fully antagonistic major histocompatibility complex ligands elicit Th0 differentiation. Differentiation of Th2 T cells may continue in the extrathymic tissues upon continued interactions with self major histocompatibility complex ligands having mixed agonist/ antagonist properties. By this mechanism, each 'hole' in the repertoire will develop an inhibitory surround comprised to Th2 T cell clones having partial reactivities to a particular self major histocompatibility complex ligand. During immune responses to self-mimicking foreign antigens, the more numerous Th2 T cells of the inhibitory surround would prevent clonal expansion and Th1 differentiation of any fully autoreactive T cell.


Prediction of coronary artery disease risk based on multiple longitudinal biomarkers.
In the last decade, few topics in the area of cardiovascular disease (CVD) research have received as much attention as risk prediction. One of the well-documented risk factors for CVD is high blood pressure (BP). Traditional CVD risk prediction models consider BP levels measured at a single time and such models form the basis for current clinical guidelines for CVD prevention. However, in clinical practice, BP levels are often observed and recorded in a longitudinal fashion. Information on BP trajectories can be powerful predictors for CVD events. We consider joint modeling of time to coronary artery disease and individual longitudinal measures of systolic and diastolic BPs in a primary care cohort with up to 20 years of follow-up. We applied novel prediction metrics to assess the predictive performance of joint models. Predictive performances of proposed joint models and other models were assessed via simulations and illustrated using the primary care cohort.


Extraction of fumonisins B1 and B2 from white rice flour and their stability in white rice flour, cornstarch, cornmeal, and glucose.
To extract fumonisin B1 (FB1) and fumonisin B2 (FB2) from Thai white rice flour, different solvent mixtures, temperatures, pH values, and addition of enzymes or ethylenediaminetetraacetic acid disodium salt (Na2EDTA) were examined. Three extractions with 0.1 M Na2EDTA achieved the highest recoveries. Initial recoveries of fumonisins added to white rice flour, cornstarch, cornmeal, and glucose varied with commodity. Fumonisins disappeared in Thai white rice flour after 12 h, but 55% remained in another white rice flour. With cornstarch 20-30% fumonisins remained after 24 h; only 43% of 14C-labeled FB1 materials extracted from cornstarch was eluted with methanol from an immunoaffinity column. Fumonisins were stable in cornmeal for 24 h but only approximately 50% remained after 30 days. With glucose, 25% of FB1 and FB2 remained 24 h after addition; N-(1-deoxy-D-fructos-1-yl)FB(1) andN-(carboxymethyl)FB(1) were detected in lower amounts than residual FB(1) after 3 months.


Stimulus deprivation amblyopia in children. Sensitivity, plasticity, and elasticity (SPE).
In the SPE model we propose, sensitivity (S) to deprivation results in changes that may be either plastic (P) (permanent) or elastic (E) (temporary). The effects of various levels (hours per day) of monocular occlusion in amblyopic children are measured as the change in visual acuity in each eye. At the patching level extremes (12 or more hours per day, zero hours per day) the effects on visual acuity in the two eyes are reciprocal, but nearly equal (symmetrical). At intermediate levels of occlusion, the asymmetries in effects necessary for successful occlusion can be demonstrated. Additional measurements of SPE parameters in children may allow for the determination of occlusion dose response whereby the risks of occlusion amblyopia and interference with binocularity may be avoided.


Measuring memory: A survey of neuropsychological practice amongst New Zealand psychologists.
This study sought to explore patterns of memory assessment in neuropsychological practice within New Zealand (NZ), to compare it to that previously described in Europe, North America and Australia, and to consider the implications for neuropsychology training in NZ. 80 NZ-registered psychologists completed an online survey asking them how frequently they utilized 50 commonly used tests of memory. Participants were also asked about their main areas of specialty, work context and demographic information. Whilst participants appeared, broadly, to utilize a similar set of 'core' tests to their colleagues in Europe, Australia and North America, there were a number of tests and test domains that were rarely utilized by NZ psychologists, in contrast to overseas samples. Furthermore, several of the tests in common usage have been shown to have significant validity issues for use with an NZ population. Overall, this study suggests that most NZ psychologists employ a similar approach to memory assessment, typically relying upon a small number of well-known tests. This appears to contrast with a greater variability of practice shown in studies of European, North American and Australian psychologists and raises several interesting questions for the future development of neuropsychology in NZ.


'Front-loaded' head-up tilt table testing: validation of a rapid first line nitrate-provoked tilt protocol for the diagnosis of vasovagal syncope.
Head-up tilt testing is the investigation of choice in the diagnosis of vasovagal syncope. The test is time consuming and labour intensive, with conventional tilt testing taking up to 45 min. We compared a shortened 'front-loaded' 20-min glyceryl trinitrate-provoked head-up tilt (FLGTN-HUT) with the standard 40-min passive tilt (HUT) as first line investigations in patients with unexplained syncope and asymptomatic controls. In the study, 149 consecutive patients with unexplained syncope and 83 asymptomatic controls were enrolled. Subjects were randomly assigned to FLGTN-HUT (800 mcg, metred spray) or HUT, then the opposite tilt-test 1 week later. Seventeen (11.4%) patients had diagnostic haemodynamic changes and symptom reproduction during HUT and 54 (36.2%) during FLGTN-HUT. A total of 24.8% more patients had a positive test with FLGTN-HUT than with passive HUT (95% CI: 16.3%, 33.4%). Nine (10.8%) controls had significant haemodynamic changes during HUT and 23 (27.7%) during GTN provocation. Seven controls had haemodynamic changes on both HUT and FLGTN-HUT testing. The controls group had 16.8% more significant haemodynamic changes with FLGTN-HUT than with HUT (95% CI: 0.06, 27.4). The front-loaded GTN protocol provided a higher diagnostic rate than passive tilt testing, and provides a rapid alternative to conventional methods, though false positivity rates are higher.


Neural responses to silent lipreading in normal hearing male and female subjects.
In the past, researchers investigated silent lipreading in normal hearing subjects with functional neuroimaging tools and showed how the brain processes visual stimuli that are normally accompanied by an auditory counterpart. Previously, we showed activation differences between males and females in primary auditory cortex during silent lipreading, i.e. only the female group significantly activated the primary auditory region during lipreading. Here we report and discuss the overall activation pattern in males and females. We used positron emission tomography to study silent lipreading in 19 normal hearing subjects (nine females). Prior to scanning, subjects were tested on their lipreading ability and only good lipreaders were included in the study. Silent lipreading was compared with a static image. In the whole group, activations were found mainly in the left hemisphere with major clusters in superior temporal, inferior parietal, inferior frontal and precentral regions. The female group showed more clusters and these clusters were larger than in the male group. Sex differences were found mainly in right inferior frontal and left inferior parietal regions and to a lesser extent in bilateral angular and precentral gyri. The sex differences in the parietal multimodal region support our previous hypothesis that the male and female brain process visual speech stimuli differently without differences in overt lipreading ability. Specifically, females associate the visual speech image with the corresponding auditory speech sound whereas males focus more on the visual image itself.


Workplace harassment, services utilization, and drinking outcomes.
Given the negative outcomes associated with sexual harassment (SH) and generalized nonsexual workplace harassment (GWH), this study examines the relationship between SH and GWH and help-seeking behavior in a sample of 2,038 university employees. Employees who experienced SH or GWH were more likely to report having sought mental health or health services to deal with workplace issues, compared with those who did not experience SH or GWH, controlling for job stress and prior services use. Women experiencing GWH were more likely to use services than men, but the same was not true for SH. Men experiencing SH who sought services exhibited higher levels of some alcohol outcomes, contrary to expectations. Implications for workplace interventions and for service providers are discussed.


Production and characterization of a pig line transgenic for human membrane cofactor protein.
A pig line transgenic for human membrane cofactor protein (hMCP) has been established. Offspring from the founder were produced by crossing the founder with pigs heterozygous for the human decay accelerating factor (hDAF) transgene. As a result, pigs transgenic for both hMCP and hDAF have been produced. Ribonuclease protection assay (RPA) indicated that hMCP was expressed in all the tissues analysed. In addition, immunohistochemical results indicated a high level of expression of hMCP on neural tissues and islets where hDAF was absent or weakly expressed. C3 fragment deposition and cytotoxicity assays indicated that hMCP expression alone on pig endothelial cells and peripheral blood lymphocytes (PBLs) provided protection against human complement mediated damage. However, we did not find that porcine endothelial cells expressing both hDAF and hMCP were better protected than those expressing hDAF alone. The expression of hMCP on tissues where hDAF is not expressed could provide these tissues with protection against human complement mediated lysis.


The aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer.
The impact of alcohol on the risk of stomach cancer is controversial. Although aldehyde dehydrogenase 2 (ALDH2) Glu504Lys (rs671) polymorphism has a strong effect on acetaldehyde metabolism, little is known about its impact on stomach cancer risk when combined with alcohol drinking. This case-control study included a total of 697 incident stomach cancer case subjects and 1372 non-cancer control subjects who visited Aichi Cancer Center between 2001 and 2005. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2 genotypes and alcohol consumption using logistic regression models after adjustment for potential confounders, including Helicobacter pylori infection. The ALDH2 504Lys allele was associated with the risk of stomach cancer, with adjusted ORs of 1.40 (95% CI, 1.11-1.76) for Glu/Lys and 1.73 (1.12-2.68) for Lys/Lys compared with Glu/Glu. Heavy drinking was associated with risk (OR 1.72, 1.17-2.52) after adjustment for ALDH2 genotype and other confounders. Moreover, ORs for heavy drinking were 1.28 (0.77-2.12) for those with ALDH2 Glu/Glu and 3.93 (1.99-5.79) for those with the ALDH2 Lys allele relative to non-drinkers with the Glu/Glu genotype (P for interaction = 0.0054). In conclusion, ALDH2 and alcohol drinking showed interaction for risk factors of stomach cancer, indicating that acetaldehyde plays a role in stomach carcinogenesis.


In search of the chemical basis for MHC odourtypes.
Mice can discriminate between chemosignals of individuals based solely on genetic differences confined to the major histocompatibility complex (MHC). Two different sets of compounds have been suggested: volatile compounds and non-volatile peptides. Here, we focus on volatiles and review a number of publications that have identified MHC-regulated compounds in inbred laboratory mice. Surprisingly, there is little agreement among different studies as to the identity of these compounds. One recent approach to specifying MHC-regulated compounds is to study volatile urinary profiles in mouse strains with varying MHC types, genetic backgrounds and different diets. An unexpected finding from these studies is that the concentrations of numerous compounds are influenced by interactions among these variables. As a result, only a few compounds can be identified that are consistently regulated by MHC variation alone. Nevertheless, since trained animals are readily able to discriminate the MHC differences, it is apparent that chemical studies are somehow missing important information underlying mouse recognition of MHC odourtypes. To make progress in this area, we propose a focus on the search for behaviourally relevant odourants rather than a random search for volatiles that are regulated by MHC variation. Furthermore, there is a need to consider a 'combinatorial odour recognition' code whereby patterns of volatile metabolites (the basis for odours) specify MHC odourtypes.


Leucocyte adhesion defect-1.
Leucocyte adhesion defect (LAD) is an inherited disorder of phagocytic function. It is characterized by inability of the leucocytes, in particular neutrophilis to migrate from the blood stream towards sites of inflammation. LAD -1 is characterized by the absence of b 2 integrins (CD 11 / CD18) on leucocytes. This disorder is characterized by delayed separation of the umbilical cord, recurrent severe infections, periodontitis, and delayed wound healing. We report an infant where the diagnosis was confirmed by flow cytometry.


Waldenström macroglobulinemia: MR imaging of the spine and CT of the abdomen and pelvis.
Twenty-three consecutive patients with Waldenström macroglobulinemia were studied with magnetic resonance (MR) imaging of the spine and computed tomography (CT) of the abdomen and pelvis. MR imaging studies included sagittal T1-weighted and gradient-recalled-echo sequences performed with and without contrast material enhancement. Marrow involvement was identified with MR imaging in 21 of 23 (91%) patients. Diffuse involvement was noted in 13 patients (56%), and a variegated pattern in eight (35%). CT demonstrated enlarged nodes in 10 of 23 (43%) patients. Correlation of MR imaging patterns and presence of adenopathy at CT with standard laboratory values for Waldenström macroglobulinemia revealed an association of the diffuse MR imaging pattern of marrow involvement and the presence of enlarged nodes at CT with more advanced disease. MR imaging of the spine and CT are reliable means of evaluation of disease status in Waldenström macroglobulinemia. They may be employed as additional means in the staging of Waldenström macroglobulinemia and may be helpful in the follow-up of patients with this rare hematologic malignancy.


Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia.
Dopaminergic neuromodulation is critically important for brain and cognitive integrity. The DRD2/ANKK1 Taq1A polymorphism is associated with striatal dopamine (DA) D2 receptor availability. Some previous studies have found that the A allele of the Taq1A polymorphism influences brain structure, but the results are inconsistent, likely due to population heterogeneity and small sample sizes. We investigated the genetic effect on caudate volume in a large sample of older adults without dementia. Results show that A-allele carriers have smaller caudate volume compared to non-carriers in relatively older adults (n = 167; Mage = 77.8 years), whereas the genotype did not influence caudate volume in a younger age group (n = 220; Mage = 62.8 years). Cognitive performance was not significantly affected by the DRD2 gene. Our findings extend previous observations by showing magnified genetic effects on brain volume in old age, and provide evidence for a link between a DA-related genetic polymorphism and grey matter volume in a brain region within the nigrostriatal dopaminergic pathway.


Shared decision making in Spain: Supportive policies and research initiatives, trends and directions for future.
Patients' rights to autonomy, information and participation in their own health care are recognized in the Spanish legal system from the early 2000's. Public institutions have progressively launched several initiatives to promote and improve patients' empowerment and self-care. However, the concept of shared decision making (SDM), although embedded in the more general concept of "active/empowered patient", usually has not been specifically advocated as an essential requisite for improving the quality of health services, either in the legal normative or the existing educational proposals. Research on SDM and the development of Patient Decision Aids (PtDAs) has increasingly grown and currently there are several of these materials available for patients with different diseases. Along with this research activity, the growing interest of patients and professionals in patient participation and SDM makes us optimistic about a gradual development of this care model in the medium term. However, there are several limitations and challenges that must be overcome in the near future. The implementation of PtDAs in clinical practice is imperative and issues such as their inclusion in clinical guidelines and electronic medical records should be encouraged. Concurrently, it is necessary to train professionals in SDM skills and the use of encounter PtDAs.