Detection of African swine fever virus in the tissues of asymptomatic pigs in smallholder farming systems along the Kenya-Uganda border: implications for transmission in endemic areas and ASF surveillance in East Africa.
The persistence of African swine fever virus (ASFV) in endemic areas, with small-scale but regular outbreaks in domestic pigs, is not well understood. ASFV has not been detected using conventional diagnosis in these pigs or adjacent populations of resistant African wild pigs, that could act as potential carriers during the outbreaks. However, such data are crucial for the design of evidence-based control strategies. We conducted cross-sectional (1107 pigs) and longitudinal (100 pigs) monitoring of ASFV prevalence in local pigs in Kenya and Uganda. The horizontal survey revealed no evidence of ASFV in the serum or blood using either conventional or real-time PCR. One pig consistently tested positive using ELISA, but negative using PCR assays on blood. Interestingly, the isotype of the antibodies from this animal were strongly IgA biased relative to control domestic pigs and warthogs, suggesting a role for mucosal immunity. The tissues from this pig were positive by PCR following post-mortem. Internal organ tissues of 44 healthy pigs (28 sentinel pigs and 16 pigs from slaughter slabs) were tested with four different PCR assays; 15.9 % were positive for ASFV suggesting that healthy pigs carrying ASFV exist in the swine population in the study area. P72 and p54 genotyping of ASFV revealed very limited diversity: all were classified in genotype IX at both loci, as were virtually all viruses causing recent ASF outbreaks in the region. Our study suggests that carrier pigs may play a role in ASF disease outbreaks, although the triggers for outbreaks remain unclear and require further investigation. This study significantly increases scientific knowledge of the epidemiology of ASF in the field in Africa, which will contribute to the design of effective surveillance and control strategies.


Effect of chemotherapy, vaccines and immunostimulants on innate immunity of goldfish infected with Aeromonas hydrophila.
We report the effect of various chemicals, vaccines and immunostimulants on innate immune mechanisms such as phagocytosis activity, superoxide anion production of blood leukocytes, complement activity and plasma lysozyme activity and disease resistance in goldfish Carassius auratus (23 +/- 2 g) against Aeromonas hydrophila on Days 15 and 30 post-infection. In infected fish, the administration of diets supplemented with either probiotics, tri-herbal extract or azadirachtin for 30 d significantly enhanced phagocytic activity; administration for 15 d had no effect. In fish treated with heat-killed and formalin-killed vaccines, and probiotics-, tri-herbal- and azadirachtin-supplemented diets, superoxide anion production was enhanced on Day 30. However, there was no superoxide anion production in fish treated with tetracycline, furanace, formalin or hydrogen peroxide. Complement activity was also significantly enhanced on Days 15 and 30 in fish groups treated with vaccine and probiotics-, tri-herbal- and azadirachtin-supplemented diets. Other groups had no complement activity. Lysozyme activity was significantly enhanced after 30 d in fish treated with heat-killed vaccine and probiotics-, tri-herbal- and azadirachtin-supplemented diets. The probiotics- and tri-herbal-containing diet administration groups had no mortality (0%) preceding the challenge with live A. hydrophila. Groups treated with heat- or formalin-killed vaccines or azadirachtin-supplemented diet suffered mortalities of 30, 35 and 10%, respectively, which represents an improvement of survival rate compared to untreated infected control groups. We conclude that probiotics-, tri-herbal- and azadirachtin-supplemented diets act as immunostimulants enhancing the goldfish innate immune response and disease resistance against A. hydrophila.


Cortisol Excess in Patients With Primary Aldosteronism Impacts Left Ventricular Hypertrophy.
Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared with matched essential hypertensives. In recent studies frequent cosecretion of cortisol and aldosterone has been reported in patients with PA. Our aim was to investigate the impact of cortisol cosecretion on LVH in patients with PA. We determined 24-hour excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and 1 year after initiation of treatment of PA. We included 73 patients from the Munich center of the German Conn's registry: 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. At the time of diagnosis, 85% of patients with PA showed LVH according to left ventricular mass index [(LVMI); median 62.4 g/m2.7]. LVMI correlated positively with total glucocorticoid excretion (r2 = 0.076, P = 0.018) as well as with tetrahydroaldosterone excretion (r2 = 0.070, P = 0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (P < 0.001) whereas mineralocorticoid receptor antagonist therapy in bilateral adrenal patients with hyperplasia reduced LVMI to a lesser degree (P = 0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion.


Evaluation of Central and Peripheral Retinal Vascular Changes in the Fellow Eyes of Patients with Unilateral Retinal Vein Occlusions.
To evaluate the subtle peripheral retinal and macular vascular changes in the fellow eyes of patients with unilateral retinal vein occlusion (RVO). This retrospective study included 53 patients with unilateral RVO and 44 age-matched controls. The frequency of peripheral retinal vascular pathologies in both eyes was evaluated using high quality ultra-wide field fluorescein angiography (UWFFA). Macular vascular density, flow area, and foveal avascular zone measurements from optical coherence tomography angiography (OCTA) were analyzed together with laser flare photometry values in patients and controls. Peripheral retinal vascular pathologies were detected on UWFFA in the fellow eyes of 36 (67.9%) patients. No significant central vascular pathologies were detected on OCTA and there was no significant difference in OCTA parameters between the fellow eyes and the controls. Flare values did not differ significantly between the control and the fellow eyes. Two thirds of the fellow eyes of unilateral RVO patients had subtle peripheral retinal vascular changes, while there was no significant microvascular change detected with OCTA in the macula. This suggests that vascular changes caused by systemic vascular disorders probably first start in the peripheral retina of the fellow eyes of patients with RVO.


The Changed Proportion of CD45RA+/CD45RO+ T Cells in Chronic Hepatitis C Patients During Pegylated Interferon-α with Ribavirin Therapy.
Infection with the hepatitis C virus (HCV) may progress toward chronic hepatitis, liver cirrhosis, and liver cancer. A therapy for patients with chronic HCV infection is the combination of pegylated interferon-α with ribavirin, which increases the rate of sustained virological response (SVR) to 56%. However, a practical biomarker to predict SVR is lacking. T cells expressing the CD45RA isoform are considered naive, and antigenic stimulation converts them to CD45RO+. CD45RO+ T cells exhibit immediate response and high lymphokine production, leading to the maintenance and upregulation of immune reactions. The aim of this study is to clarify the proportions of CD45RA+ and CD45RO+ T cells associated with rapid virological response and SVR. We collected blood samples from 32 HCV patients receiving the combined treatment. The samples were collected before, during 4th, 12th, and 24th therapy weeks, and 4th week posttherapy, and their T cell populations were analyzed using flow cytometry. Twenty-nine patients (90.6%) achieved SVR. There were significant declines in proportions of CD45RA+ cells during 4th, 12th, and 24th therapy weeks, and significant increases in proportions of CD45RO+ cells during 24th therapy week and 4th week posttherapy (P < 0.05). Patients undergoing hepatitis C therapy exhibited lowered CD45RA+ cell proportions and increased CD45RO+ cell proportions. This effect may be important in a patient's response to pegylated interferon-α with ribavirin therapy.


AMPK promotes skeletal muscle autophagy through activation of forkhead FoxO3a and interaction with Ulk1.
In skeletal muscle, protein levels are determined by relative rates of protein synthesis and breakdown. The balance between synthesis and degradation of intracellular components determines the overall muscle fiber size. AMP-activated protein kinase (AMPK), a sensor of cellular energy status, was recently shown to increase myofibrillar protein degradation through the expression of MAFbx and MuRF1. In the present study, the effect of AMPK activation by AICAR on autophagy was investigated in muscle cells. Our results show that FoxO3a transcription factor activation by AMPK induces the expression of the autophagy-related proteins LC3B-II, Gabarapl1, and Beclin1 in primary mouse skeletal muscle myotubes and in the Tibialis anterior (TA) muscle. Time course studies reveal that AMPK activation by AICAR leads to a transient nuclear relocalization of FoxO3a followed by an increase of its cytosolic level. Moreover, AMPK activation leads to the inhibition of mTORC1 and its subsequent dissociation of Ulk1, Atg13, and FIP200 complex. Interestingly, we identify Ulk1 as a new interacting partner of AMPK in muscle cells and we show that Ulk1 is associated with AMPK under normal conditions and dissociates from AMPK during autophagy process. Moreover, we find that AMPK phosphorylates FoxO3a and Ulk1. In conclusion, our data show that AMPK activation stimulates autophagy in skeletal muscle cells through its effects on the transcriptional function of FoxO3a and takes part in the initiation of autophagosome formation by interacting with Ulk1. Here, we present new evidences that AMPK plays a crucial role in the fine tuning of protein expression programs that control skeletal muscle mass.


Who should receive recombinant human erythropoietin?
The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.


Partial purification and properties of a mannofructokinase from Streptococcus mutans SL-1.
Fructokinase activity was demonstrated in seven strains of oral streptococci. The enzyme purified from Streptococcus mutans SL-1 was capable of phosphorylating both D-fructose and D-mmannose to their respective 6-phosphates. Phosphorylation of both fructose and mannose was dependent on adenosine 5'-triphosphate and a divalent metal ion. The molecular weight of the purified enzyme was estimated to be 49,000. The apparent Km of the enzyme for fructose was 0.63 mM. This enzyme also utilized mannose as a substrate, with an apparent Km for mannose of 0.37 mM. Since the activities of the enzyme toward mannose and fructose were not separated upon purification of the enzyme and since mannose was a competitive inhibitor of fructose phosphorylation, the purified kinase is a single enzyme, mannofructokinase, with dual specificity for both mannose and fructose. A role for this enzyme in carbohydrate metabolism in S. mutans is postulated.


Pre-attention and Working Memory in ADHD: A 25-Year Follow-Up Study.
Objective: The aim of the study was to compare the development of working memory and preliminary stages of attentional processing in individuals with ADHD over a 23- to 25-year period. Method: Individuals with ADHD (n = 19) and healthy controls (n = 26) were followed up after 13 years (T2) and 23 to 25 years (T3) after initial assessment (T1). They were reassessed with diagnostic measures and the Backward masking task (pre-attention) and the Digit span distractibility test with and without distraction conditions (working memory). Results: The ADHD group performed below the healthy controls on all time points on the Digit span distractibility test. On the distractibility condition, we found a selective decline in performance from T2 to T3 for the ADHD group. Conclusion: The results highlight that ADHD individuals continue to display working memory deficits, also in adulthood, thus creating an imperative for cognitive rehabilitation techniques to help address attention difficulties.


T-Cell Deletion of MyD88 Connects IL17 and IκBζ to RAS Oncogenesis.
Cancer development requires a favorable tissue microenvironment. By deleting Myd88 in keratinocytes or specific bone marrow subpopulations in oncogenic RAS-mediated skin carcinogenesis, we show that IL17 from infiltrating T cells and IκBζ signaling in keratinocytes are essential to produce a permissive microenvironment and tumor formation. Both normal and RAS-transformed keratinocytes respond to tumor promoters by activating canonical NF-κB and IκBζ signaling, releasing specific cytokines and chemokines that attract Th17 cells through MyD88-dependent signaling in T cells. The release of IL17 into the microenvironment elevates IκBζ in normal and RAS-transformed keratinocytes. Activation of IκBζ signaling is required for the expression of specific promoting factors induced by IL17 in normal keratinocytes and constitutively expressed in RAS-initiated keratinocytes. Deletion of Nfkbiz in keratinocytes impairs RAS-mediated benign tumor formation. Transcriptional profiling and gene set enrichment analysis of IκBζ-deficient RAS-initiated keratinocytes indicate that IκBζ signaling is common for RAS transformation of multiple epithelial cancers. Probing The Cancer Genome Atlas datasets using this transcriptional profile indicates that reduction of IκBζ signaling during cancer progression associates with poor prognosis in RAS-driven human cancers. IMPLICATIONS: The paradox that elevation of IκBζ and stimulation of IκBζ signaling through tumor extrinsic factors is required for RAS-mediated benign tumor formation while relative IκBζ expression is reduced in advanced cancers with poor prognosis implies that tumor cells switch from microenvironmental dependency early in carcinogenesis to cell-autonomous pathways during cancer progression.


Inpatient data, inevitable need for policy making at national and sub-national levels: a lesson learned from NASBOD.
Estimating burden of disease, injuries and risk factors is crucial for health policy decision making. The Burden of Diseases (BoD) studies provide data about the magnitude and distribution of health problems among the population at national and sub-national levels. The BoD studies are designed to use secondary data for estimating prevalence and incidence of diseases, injuries and risk factors. However, due to the scarcity of data sometimes it becomes unavoidable to collect data from medical records. Among all needed source of data, including surveys, registries, censuses, inpatient and outpatient data, hospital data are an essential source for BoD studies. Hospital Data Survey (HDS) aims to estimate the prevalence and incidence of diseases and injuries that led to admission to hospitals. This paper aims to describe the required steps for data gathering, sampling, analytical methods, and other needed procedures for HDS. The designed questionnaire includes demographic data, current health status, diseases, injuries and co-morbidities with their ICD10 codes, curative procedures, and treatment. A pilot study was conducted on 302 medical records from 6 hospitals to evaluate the validity and reliability of the questionnaire. Sampling frame was designed and probability proportional was used after being tested in the pilot study. In the next step, we will collect 367500 medical files from 863 hospitals (0.5% of all inpatient records in hospitals from1996 - 2013). The HDS is the first national study in Iran that is gathering data through an online-offline web-based system based on electronic version of the questionnaire which makes the process of data cleaning and analyses more comfortable.


Considerations in ethnic rhinoplasty.
Although it is difficult to define specific ethnic groups as they are multiracial mixtures determined by historical, geographical, and cultural factors, we can define basically five non-Caucasian groups that commonly request rhinoplasty. The specific anatomy, surgical options, implant material, grafts, and possible complications are discussed. The importance of blending the "new" nose with the ethnic features to achieve harmony in the facial aesthetic components is emphasized.


Is policy well-targeted to remedy financial strain among caregivers of severely injured U.S. service members?
U.S. military service members have sustained severe injuries since the start of the wars in Iraq and Afghanistan. This paper aims to determine the factors associated with financial strain of their caregivers and establish whether recent federal legislation targets caregivers experiencing financial strain. In our national survey, 62.3% of caregivers depleted assets and/or accumulated debt, and 41% of working caregivers left the labor force. If a severely injured veteran needed intensive help, the primary caregiver faced odds 4.63 times higher of leaving the labor force, and used $27,576 more in assets and/or accumulated debt compared to caregivers of veterans needing little or no assistance.


Integrating transcriptomics and biochemical analysis to understand the interactive mechanisms of the coexisting exposure of nanoplastics and erythromycin on Chlorella pyrenoidosa.
Nanoplastics and antibiotics frequently co-exist in water polluted by algal blooms, but little information is available about interaction between substances. Erythromycin, as a representative of antibiotics, has been frequently detected in aquatic environments. This investigation attempted to reveal the interaction mechanism of nanoplastics and erythromycin on Chlorella pyrenoidosa. Results demonstrated that the joint toxicity of erythromycin and nanoplastics was dynamic and depended on nanoplastics concentration. Antagonistic effects of 1/2 or 1 EC50 erythromycin and nanoplastic concentration (10 mg/L) on the growth of C. pyrenoidosa was observed. The joint toxicity of 1/2 or 1 EC50 erythromycin and nanoplastic concentration (50 mg/L) was initially synergistic during 24-48 h and then turned to antagonistic during 72-96 h. Consequently, antagonistic effect was the endpoint for joint toxicity. Integration of transcriptomics and physiological biochemical analysis indicated that the co-existence of nanoplastics and erythromycin affected the signal transduction and molecular transport of algal cell membrane, induced intracellular oxidative stress, and hindered photosynthetic efficiency. Overall, this study provided a theoretical basis for evaluating the interactive mechanisms of nanoplastics and antibiotics.


Dopaminergic Modulation of Sensory Attenuation in Parkinson's Disease: Is There an Underlying Modulation of Beta Power?
Background and Aims: Pathological high amplitude of beta oscillations is thought as the underlying mechanism of motor symptoms in Parkinson's disease (PD), in particular with regard to bradykinesia. In addition, abnormality in a neurophysiological phenomenon labeled sensory attenuation has been found in patients with PD. The current study explored the hypothesis that the abnormal sensory attenuation has a causal link with the typical abnormality in beta oscillations in PD. Methods: The study tested sixteen right-handed patients with a diagnosis of PD and 22 healthy participants, which were matched by age and gender. Somatosensory evoked potentials were elicited through electrical stimulation of the median nerve at the wrist. Electrical activity was recorded at the scalp using a 128 channels EEG. Somatosensory evoked potentials were recorded in 2 conditions: at rest and at the onset of a voluntary movement, which was a self-paced abduction movement of the right thumb. Results: Healthy participants showed a reduction of the N20-P25 amplitude at the onset of the right thumb abduction compared to the rest condition (P < 0.05). When patients were OFF medication, they showed mild reduction of the N20-P25 component at movement onset (P < 0.05). On the contrary, they did show greater attenuation of the N20-P25 component at the onset of movement compared to the rest condition when ON medication (P < 0.05). There was no significant evidence of a link between the degree of sensory attenuation and the change in beta oscillations in our cohort of patients. Conclusion: These results confirmed a significant link between dopaminergic modulation and sensory attenuation. However, the sensory attenuation and beta oscillations were found as two independent phenomena.


A general nickel-catalyzed hydroamination of 1,3-dienes by alkylamines: catalyst selection, scope, and mechanism.
A simple colorimetric assay of various transition-metal catalysts showed that the combination of DPPF, Ni(COD)(2), and acid is a highly active catalyst system for the hydroamination of dienes by alkylamines to form allylic amines. The scope of the reaction is broad; various primary and secondary alkylamines react with 1,3-dienes in the presence of these catalysts. Detailed mechanistic studies revealed the individual steps involved in the catalytic process. These studies uncovered unexpected thermodynamics for the addition of amines to pi-allyl nickel complexes: instead of the thermodynamics favoring the reaction of a nickel allyl with an amine to form an allylic amine, the thermodynamics favored reaction of a nickel(0) complex with allylic amine in the presence of acid to form a Ni(II) allyl. The realization of these thermodynamics led us to the discovery that nickel and some palladium complexes in the presence or absence of acid catalyze the exchange of the amino groups of allylic amines with free amines. This exchange process was used to reveal the relative thermodynamic stabilities of various allylic amines. In addition, this exchange reaction leads to racemization of allylic amines. Therefore, the relative rate for C-N bond formation and cleavage influences the enantioselectivity of diene hydroaminations.


Revealing of Core Shell Effect on Frequency-Dependent Properties of Bi-based Relaxor/Ferroelectric Ceramic Composites.
In this study, electromechanical characteristics of (1-x) Bi0.5Na0.5TiO3-xSrTiO3 (ST26, x = 0.26)/(1-y) Bi0.5Na0.5TiO3-ySrTiO3 (ST10, y = 0.1) (matrix/seed) composites were studied. The ST26 (high relaxor phase) and ST10 (a relaxor ferroelectric (RF), high ferroelectric phase) composite with large (r-ST26-ST10) and small (t-ST26-ST10) grains exhibited frequency-related dielectric properties and large strain response at a low triggering electric field (an incipient piezoelectricity). It is ascribed to a matrix-seed effect originating from the inhomogeneous composition due to the presence of two phases. The r-ST26-ST10 composite sintered at 4 h, prominent material, showed a high normalized dynamic strain (d33*) of ~700 pm/V (large grains) with stable frequency dependence properties at a low field of 40 kV/cm. The properties of the r-ST26-ST10 composite exhibit less decay with frequency-related polarization and strain compared to those of t-ST26-ST10 composite. The increase in soaking time promotes the diffusion and homogenization of the microstructure in composites, leading to changes in the core-shell structure in the solid solution. The polarization and strain of the ST26-ST10 composites with the frequency are linked to the stability of the internal random fields created by non-ergodic relaxor phase of seed and the amount of phase change in the ergodic relaxor matrix.


An analysis of atrophy in the medial mammillary nucleus following hippocampal and fornix lesions in humans and nonhuman primates.
Lesions of the hippocampal formation or transections of the fornix are followed by shrinkage of the medial mammillary nucleus (MMN). We determined whether the shrinkage of this nucleus was due to loss and/or shrinkage of neurons in addition to the loss of neuropil. We examined the MMN in a patient (KB) with an infarct that led to marked atrophy of the left hippocampus and subiculum, leaving the right MMN intact. Unbiased, stereological measurement techniques were used to compare the total cell number and individual neuronal cross-sectional areas in both left and right MMN in this patient and in two control human brains. We also analyzed the MMN in four macaque monkeys that underwent experimental unilateral transections of the fornix. The volume of the MMN on the lesioned side in KB was 55% of the unlesioned side (2.8 mm(3) vs 5.1 mm(3)); the MMN in the monkey cases were reduced to 47-58% of the volume of the nonlesioned side. Neurons in the deafferented MMN of KB and of the monkey subjects were decreased in cross-sectional area (16-20%, P < 0.0001). There was a trend toward decreased cell numbers (11-15%) on the lesioned side in all cases. We have estimated that the loss in cell number and shrinkage of remaining cells contribute negligibly to the 45% reduction in MMN volume. Therefore, the loss of neuropil (dendrites and afferent and efferent axons) appears to be the major contributor to the change in MMN volume.


The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria.
Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups.


The Association of Delayed Care With Depression Among US Middle-Aged and Older Adults During the COVID-19 Pandemic: Cross-sectional Analysis.
During the COVID-19 pandemic, the depression level among US adults has significantly increased. Age disparity in depression during the pandemic has been reported in recent studies. Delay or avoidance of medical care is one of the collateral damages associated with the COVID-19 pandemic, and it can lead to increased morbidity and mortality. This study aimed to assess the prevalence of depression and delayed care among US middle-aged adults and older adults during the pandemic, as well as investigate the association of delayed care with depression among those 2 age groups. This cross-sectional study used data from the 2020 Health and Retirement Study (HRS) COVID-19 Project (Early, Version 1.0). Univariate analyses, bivariate analyses, and binary logistic regression were applied. US adults older than 46 years were included. Depression was measured by the Composite International Diagnostic Interview-Short Form (CIDI-SF). Delayed care was measured by the following 4 items: delayed surgery, delayed seeing a doctor, delayed dental care, and other delayed care. A total of 3246 participants were identified. More than half of the participants were older than 65 years (n=1890, 58.2%), and 274 (8.8%) participants had depression during the pandemic. Delayed dental care was positively associated with depression among both middle-aged adults (OR 2.05, 95% CI 1.04-4.03; P=.04) and older adults (OR 3.08, 95% CI 1.07-8.87; P=.04). Delayed surgery was positively associated with depression among older adults (OR 3.69, 95% CI 1.06-12.90; P=.04). Self-reported pain was positively related to depression among both age groups. Middle-aged adults who reported higher education levels (some college or above) or worse self-reported health had a higher likelihood of having depression. While perceived more loneliness was positively associated with depression among older adults, financial difficulty was positively associated with depression among middle-aged adults. This study found that depression was prevalent among middle-aged and older adults during the pandemic. The study highlighted the collateral damage of the COVID-19 pandemic by identifying the association of delayed surgery and dental care with depression during the pandemic. Although surgery and dental care cannot be delivered by telehealth, telehealth services can still be provided to address patients' concerns on delayed surgery and dental care. Moreover, the implementation of telemental health services is needed to address mental health symptoms among US middle-aged and older adults during the pandemic. Future research that uses more comprehensive measurements for delayed care is needed to decipher the path through which delayed care is associated with depression.


Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential.
For reasons that are not apparent, it has been difficult to isolate and expand the adult stem cells referred to as mesenchymal stem cells or marrow stromal cells (MSCs) from murine bone marrow. We developed a protocol that provides rapidly expanding MSCs from 5 strains of inbred mice. The MSCs obtained from 5 different strains of mice were similar to human and rat MSCs in that they expanded more rapidly if plated at very low density, formed single-cell-derived colonies, and readily differentiated into either adipocytes, chondrocytes, or mineralizing cells. However, the cells from the 5 strains differed in their media requirements for optimal growth, rates of propagation, and presence of the surface epitopes CD34, stem cell antigen-1 (Sca-1), and vascular cell adhesion molecule 1 (VCAM-1). The protocol should make it possible to undertake a large number of experiments with MSCs in transgenic mice that have previously not been possible. The differences among MSCs from different strains may explain some of the conflicting data recently published on the engraftment of mouse MSCs or other bone marrow cells into nonhematopoietic tissues.


Acute ischemic stroke update.
Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for thrombolectomy are being developed, and neuroprotective therapies such as the use of magnesium, statins, and induced hypothermia are being explored. As treatment interventions become more clearly defined in special subgroups of patients, outcomes in patients with acute ischemic stroke will likely continue to improve.


Naturally occurring R.ColBM plasmids belonging to the IncFIII incompatibility group.
Two Escherichia coli strains isolated from urinary tract infections were resistant to streptomycin, kanamycin, neomycin, tetracycline and sulphonamides. The strains also produced colicins B and M. The resistance to streptomycin, kanamycin and neomycin and the ability to produce colicins B and M could be transferred to an E. coli K12 recipient. Resistance and colicinogeny markers were transferred together by conjugation, and did not segregate even after interrupted mating or phage P1-mediated transduction. Hence, the drug-resistance and colicinogeny markers were carried by the same plasmid, designated as R.ColBM plasmid. The two R.ColBM plasmids were Fi+ and produced an F-like pilus. They belonged to the IncFIII incompatibility group, being thus the first R plasmids identified in this group. The two plasmids were isolated and their molecular sizes were determined by electrophoresis in agarose gels and by contour length measurements. Both methods showed that both plasmids were about 52 megadaltons.


A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder.
In heterozygous females affected by an X-linked skin disorder, lesions often appear in a characteristic pattern, the so-called Blaschko's lines. We investigated a female Labrador Retriever and her crossbred daughter, which both showed similar clinical lesions that followed Blaschko's lines. The two male littermates of the affected daughter had died at birth, suggesting a monogenic X-chromosomal semidominant mode of inheritance. Whole genome sequencing of the affected daughter, and subsequent automated variant filtering with respect to 188 nonaffected control dogs of different breeds, revealed 332 hetero-zygous variants on the X-chromosome private to the affected dog. None of these variants was protein-changing. By visual inspection of candidate genes located on the X-chromosome, we identified a large deletion in the NSDHL gene, encoding NAD(P) dependent steroid dehydrogenase-like, a 3β-hydroxysteroid dehydrogenase involved in cholesterol biosynthesis. The deletion spanned >14 kb, and included the last three exons of the NSDHL gene. By PCR and fragment length analysis, we confirmed the presence of the variant in both affected dogs, and its absence in 50 control Labrador Retrievers. Variants in the NSDHL gene cause CHILD syndrome in humans, and the bare patches (Bpa) and striated (Str) phenotypes in mice. Taken together, our genetic data and the known role of NSDHL in X-linked skin disorders strongly suggest that the identified structural variant in the NSDHL gene is causative for the phenotype in the two affected dogs.


The higher level of complexity of K-Ras4B activation at the membrane.
Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5'-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.-Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane.


Dispositional optimism as a predictor of men's decision-related distress after localized prostate cancer.
This study investigated prospectively the relationship between optimism, threat appraisal, seeking support and information, cognitive avoidance, physical treatment side effects, and decision-related distress in 111 men with localized prostate cancer. Men were assessed at diagnosis and 2 and 12 months after treatment. Baseline decision-related distress predicted distress 2 and 12 months after treatment. Optimism was a significant prospective and concurrent predictor of decision-related distress, with the effect mediated by proximal cancer threat appraisal. Seeking support and information and cognitive avoidance were not associated with decision-related distress at any time point. For physical treatment side effects, concurrent urinary symptoms were predictive of decision-related distress 2 months after treatment. Results suggest that decision-related distress is generated by similar processes to that of the psychological distress that follows a cancer diagnosis. Screening for men with high decision-related distress for referral to in-depth decision support is suggested. Outcome expectations may present as a therapy target to increase the effectiveness of decisional support that is utility based.


Correlation between Faecal Tumour M2 Pyruvate Kinase and Colonoscopy for the Detection of Adenomatous Neoplasia in a Secondary Care Cohort.
Colorectal cancer screening programmes that target detection and excision of adenomatous colonic polyps have been shown to reduce colorectal cancer related mortality. Many screening programmes include an initial faecal occult blood test (FOBt) prior to colonoscopy. To refine the selection of patients for colonoscopy other faecal-based diagnostic tools have been proposed, including tumour M2-pyruvate kinase (tM2-PK). To determine whether tM2-PK quantification may have a role in diverse settings we have assessed the assay in a cohort of patients derived from both the England bowel cancer screening programme (BCSP) and symptomatic individuals presenting to secondary care. Patients undergoing colonoscopy provided faecal samples prior to bowel preparation. Faecal tM2-PK concentrations were measured by ELISA. Sensitivity, specificity, positive predictive value, negative predictive value and ROC analyses were calculated. Ninety-six patients returned faecal samples: 50 of these with adenomas and 7 with cancer. Median age was 68. Median faecal tM2-PK concentration was 3.8 U/mL for individuals without neoplastic findings at colonoscopy, 7.7 U/mL in those with adenomas and 24.4 U/mL in subjects with colorectal cancer (both, p=0.01). ROC analysis demonstrated an AUROC of 0.66 (sensitivity 72.4%, specificity 48.7%, positive predictive value 67.7%, negative predictive value 36.7%). Amongst BCSP patients with a prior positive FOBt faecal tM2-PK was more abundant (median 6.4 U/mL, p=0.03) and its diagnostic accuracy was greater (AUROC 0.82). Our findings confirm that faecal tM2-PK ELISA may have utility as an adjunct to FOBt in a screening context, but do not support its use in symptomatic patients.


[Technical parameters influencing the reactivity of the vascular endothelium in relation to lectin of Evonymus europaeus].
Some parameters characterizing sample preparation for coloration with lectins were investigated in the model of sheep myocardial capillaries, revealed by EEA after formol fixation and paraffin embedding. The most influential factors are: addition of lysine-periodate to paraformaldehyde, duration of fixative immersion, oldness of paraformaldehyde dilution, delay of fixation (if below 8 h). All of them happen before embedding. On the other hand, those happening later are out of influence.


Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease.
Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD), surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease. A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist. Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2), cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25). The most frequent diagnosis was usual interstitial pneumonia (UIP) (n = 7). Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications. In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield.


Identification of the human testis protein phosphatase 1 interactome.
Protein phosphorylation is a critical regulatory mechanism in cellular signalling. To this end, PP1 is a major eukaryotic serine/threonine-specific phosphatase whose cellular functions, in turn, depend on complexes it forms with PP1 interacting proteins-PIPs. The importance of the testis/sperm-enriched variant, PP1γ2, in sperm motility and spermatogenesis has previously been shown. Given the key role of PIPs, it is imperative to identify the physiologically relevant PIPs in testis and sperm. Hence, we performed Yeast Two-Hybrid screens of a human testis cDNA library using as baits the different PP1 isoforms and also a proteomic approach aimed at identifying PP1γ2 binding proteins. To the best of our knowledge this is the largest data set of the human testis PP1 interactome. We report the identification of 77 proteins in human testis and 7 proteins in human sperm that bind PP1. The data obtained increased the known PP1 interactome by reporting 72 novel interactions. Confirmation of the interaction of PP1 with 5 different proteins was also further validated by co-immunoprecipitation or protein overlays. The data here presented provides important insights towards the function of these proteins and opens new possibilities for future research. In fact, such diversity in PP1 regulators makes them excellent targets for pharmacological intervention.


Insights into the Epiphyseal Cartilage Origin and Subsequent Osseous Manifestation of Juvenile Osteochondritis Dissecans with a Modified Clinical MR Imaging Protocol: A Pilot Study.
Purpose To retrospectively determine if a modified clinical magnetic resonance (MR) imaging protocol provides information on the origin of juvenile osteochondritis dissecans (JOCD) lesions and allows for staging on the basis of the proposed natural history of JOCD to better guide clinical management of the disease. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study was performed in 13 consecutive patients (mean age, 14.9 years; age range, 10-22 years; nine male and four female patients) and one additional comparative patient (a 44-year-old man), in which 19 knees with 20 JOCD lesions were imaged. Seventeen lesions occurred in the medial femoral condyle, two occurred in the lateral femoral condyle, and one occurred in the medial trochlea. The clinical 3-T MR imaging protocol was supplemented with a routinely available multiecho gradient-recalled-echo sequence with the shortest attainable echo time of approximately 4 msec (T2* mapping). Results At the earliest manifestation, the lesion was entirely cartilaginous (n = 1). Subsequently, primary cartilaginous lesions within the epiphyseal cartilage developed a rim calcification that originated from normal subjacent bone, which defined a clear cleft between the lesion progeny and the parent bone (n = 9). Secondarily, progeny lesions became ossified (n = 7) while at the same time forming varying degrees of osseous bridging and/or clefting with the parent bone. Two healed lesions with a linear bony scar and one detached lesion were identified. Conclusion The modified MR imaging protocol allowed for identification of the epiphyseal cartilage origin and subsequent stages of ossification in JOCD. The approach allows further elucidation of the natural history of the disease and may better guide clinical management. © RSNA, 2016.


Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines.
beta-Adrenergic receptors on human mononuclear leukocytes were assessed using [125I]iodohydroxybenzylpindolol binding. Subjects were studied supine and after being ambulatory, a maneuver that increases plasma catecholamines approximately two-fold. beta-Receptor affinity for agonists, measured by the competition of [125I]iodohydroxybenzylpindolol binding by (-)isoproterenol was significantly reduced with ambulation and this reduction was associated with a reduction in the proportion of beta-receptors binding agonist with a high affinity from a mean (+/- SEM) of 42 +/- 5 to 24 +/- 2% (P less than 0.01). In a parallel series, beta-adrenergic-stimulated adenylate cyclase activity was also reduced with postural change from 4.6 +/- 1.1 to 2.4 +/- 0.6 pmol [32P]cAMP/min per mg protein (P less than 0.05) after ambulation. Similar reductions in the proportion of receptors binding agonist with a high affinity were seen after infusion of norepinephrine. We conclude that the maneuver of ambulation reduces leukocyte beta-receptor responsiveness and affinity for agonists, probably by the effect of increased plasma catecholamines mediating an uncoupling of the beta-receptor-adenylate cyclase complex.


Landmarks or panoramas: what do navigating ants attend to for guidance?
Insects are known to rely on terrestrial landmarks for navigation. Landmarks are used to chart a route or pinpoint a goal. The distant panorama, however, is often thought not to guide navigation directly during a familiar journey, but to act as a contextual cue that primes the correct memory of the landmarks. We provided Melophorus bagoti ants with a huge artificial landmark located right near the nest entrance to find out whether navigating ants focus on such a prominent visual landmark for homing guidance. When the landmark was displaced by small or large distances, ant routes were affected differently. Certain behaviours appeared inconsistent with the hypothesis that guidance was based on the landmark only. Instead, comparisons of panoramic images recorded on the field, encompassing both landmark and distal panorama, could explain most aspects of the ant behaviours. Ants navigating along a familiar route do not focus on obvious landmarks or filter out distal panoramic cues, but appear to be guided by cues covering a large area of their panoramic visual field, including both landmarks and distal panorama. Using panoramic views seems an appropriate strategy to cope with the complexity of natural scenes and the poor resolution of insects' eyes. The ability to isolate landmarks from the rest of a scene may be beyond the capacity of animals that do not possess a dedicated object-perception visual stream like primates.


Association between self-rated health and ideal cardiovascular health: The Baptist Health South Florida Employee Study.
There is increasing evidence of the role psychosocial factors play as determinants of cardiovascular health (CVH). We examined the association between self-rated health (SRH) and ideal CVH among employees of a large healthcare organization. Data were collected in 2014 from employees of Baptist Health South Florida during an annual voluntary health risk assessment and wellness fair. SRH was measured using a self-administered questionnaire where responses ranged from poor, fair, good, very good to excellent. A CVH score (the proxy for CVH) that ranged from 0 to 14 was calculated, where 0-8 indicate an inadequate score, 9-10, average and 11-14, optimal. A multinomial logistic regression was used to examine the association between SRH and CVH. Of the 9056 participants, 75% were female and mean age (SD) was 43 ± 12 years. The odds of having a higher CVH score increased as SRH improved. With participants who reported their health status as poor-fair serving as reference, adjusted odds ratios for having an optimal CVH score by the categories of SRH were: excellent, 21.04 (15.08-29.36); very good 10.04 (7.25-13.9); and good 3.63 (2.61-5.05). Favorable SRH was consistently associated with better CVH.


IDIOPATHIC SCLEROCHOROIDAL CALCIFICATIONS. A CASE REPORT.
Sclerochoroidal calcifications (SCHC) are an uncommon benign ocular condition that occurs in elderly patients. SCHC usually manifest as multiple placoid yellow lesions in the midperipheral fundus, most often in the upper temporal quadrant. They are asymptomatic and often discovered during routine eye examinations in a patient with good visual acuity and visual field. According to the etiology, SCHC are divided into idiopathic, metastatic and dystrophic. This is case report of 2 patients with idiopathic SCHC, who underwent basic eye examinations, fundus photography, optical coherence tomography, ultrasonography, fluorescein angiography, fundusautofluorescence, laboratory screening and in the second case also CT head scan. The aim of this publication is to point out the typical features of SCHC and their distinction from more serious conditions that they may resemble.


[Labelling animal vascular endothelial cells with Evonymus europaeus lectin].
Evonymus europaeus Agglutinin (EEA) marks some vascular endothelial cells in animal as in man. Bindings is identical in organs frezen or fixed by paraformaldehyde-lysine-periodate and embedded in paraffin. Monkey, swine, ox, sheep, dog, have positive cells which are not shown in rabbit, rat, mouse or hen. But monkey is the only animal to show an endothelial dimorphism with a topography analogous to the one revealed by UEA1 in man.


Modulation of function of bovine polymorphonuclear leukocytes and lymphocytes by high temperature in vitro and in vivo.
Function of polymorphonuclear leukocytes (PMNL) and proliferation of lymphocytes after stimulation with mitogens were evaluated in vitro at incubation temperatures of 38.5 and 42 C, and after in vivo heat stress of lactating Holstein cows. Cytochrome-c reduction and random migration of PMNL were reduced when cells were preincubated or incubated at 42 C, but high incubation temperature had little or no effect on phagocytosis and killing of Escherichia coli. Proliferation of lymphocytes was reduced when cells were incubated for 60 hours at 42 C after stimulation with phytohemagglutinin, pokeweed mitogen, or concanavalin A. After stimulation with phytohemagglutinin, lymphocytes were most sensitive to high temperature during the first 24 hours of the 60-hour culture period. High incubation temperature had little effect on viability of cells. In vivo heat stress had no significant effect on responses of PMNL in vitro, but the decrease in proliferation of lymphocytes in vitro at high temperature was less when cells were obtained from heat-stressed cows. Total leukocyte counts in blood and somatic cell counts in milk were higher in heat-stressed cows. Results indicate that: exposure to high temperature in vitro can depress responses of PMNL and lymphocytes; apparent adaptive mechanisms induced by in vivo heat stress provide protection from effects of high temperature seen in vitro; and evidence could not be found to support the hypothesis that reduction in immune function is the basis for increases in the incidence of mastitis during the summer.


TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats.
The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24•Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins. The affinity for Sec23 is concentrated in the proline-rich domains (PRDs) of TANGO1 and cTAGE5, but Sec23 recognizes merely a PPP motif. The PRDs contain repeated PPP motifs separated by proline-rich linkers, so a single TANGO1/cTAGE5 receptor can bind multiple copies of coat protein in a close-packed array. We propose that TANGO1/cTAGE5 promotes the accretion of inner coat proteins to the helical lattice. Furthermore, we show that PPP motifs in the outer coat protein Sec31 also bind to Sec23, suggesting that stepwise COPII coat assembly will ultimately displace TANGO1/cTAGE5 and compartmentalize its operation to the base of the growing COPII tubule.


Latent Autoimmune Diabetes in Adults: A Review on Clinical Implications and Management.
Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by a less intensive autoimmune process and a broad clinical phenotype compared to classical type 1 diabetes mellitus (T1DM), sharing features with both type 2 diabetes mellitus (T2DM) and T1DM. Since patients affected by LADA are initially insulin independent and recognizable only by testing for islet-cell autoantibodies, it could be difficult to identify LADA in clinical setting and a high misdiagnosis rate still remains among patients with T2DM. Ideally, islet-cell autoantibodies screening should be performed in subjects with newly diagnosed T2DM, ensuring a closer monitoring of those resulted positive and avoiding treatment of hyperglycaemia which might increase the rate of β-cells loss. Thus, since the autoimmune process in LADA seems to be slower than in classical T1DM, there is a wider window for new therapeutic interventions that may slow down β-cell failure. This review summarizes the current understanding of LADA, by evaluating data from most recent studies, the actual gaps in diagnosis and management. Finally, we critically highlight and discuss novel findings and future perspectives on the therapeutic approach in LADA.


Human T-lymphotropic virus type I/II infections in volunteer blood donors from Northern and Western Greece: increased prevalence in one blood bank unit.
BACKGROUND: Blood donors are routinely screened for antibodies to human T-cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) in the United States, Canada, Japan, and some European countries. Previous reports from our group in relatively small numbers of donors have shown a zero prevalence of HTLV-I/II markers in our region. In this study, seven blood banks in the north and west of Greece participated in order to determine whether mandatory screening of blood donations for HTLV-I/II infection should be established. METHODS: Sera from 51,714 consecutive donors were investigated for anti-HTLV-I/II using two commercially available enzyme immunoassays (EIAs). Reactive samples in one or both EIAs were repeatedly evaluated further by Western blot, which is specific for both confirmation and differentiation of HTLV-I and HTLV-II seroreactivities. Investigation for HTLV DNA was also done in all EIA-reactive donors, irrespective of the WB result, using a combination assay based on the polymerase chain reaction (PCR) and a DNA EIA. RESULTS: A total of 115 donors (0.222%; 95% CI 0.018-0.26%) were initially considered reactive for anti-HTLV-I/II by EIAs. However, only 7 of the 115 were confirmed as positive by WB (five HTLV-I and two HTLV-I/II). Thus, the prevalence of anti-HTLV-I/II in donors from northern and western Greece was 0.013% (95% CI 0.003-0.023%). Interestingly, the majority of WB-confirmed anti-HTLV-positive individuals were detected in the blood bank of Corfu (5/7, all anti-HTLV-I). This prevalence (5/15383; 0.032%; 95% CI 0.004-0.061%) was six times the prevalence found at the other blood banks combined (2/36331; 0.0055%; 95% CI 0-0.013%), but it was not statistically significant. None of the EIA-reactive donors had detectable HTLV DNA. CONCLUSIONS: The very low prevalence of confirmed anti-HTLV-I/II infection markers in northern and western Greek blood donors, together with the negative PCR results in EIA-reactive subjects, indicates that anti-HTLV-I/I routine screening is not really justified in this area of our country. However, the increased prevalence of WB-confirmed anti-HTLV-I-positive donors in the Corfu blood bank calls for further prospective and careful investigation in order to address whether this finding represents a real cluster phenomenon of HTLV infection.


Musculoskeletal anomalies in a large cohort of boys with 49, XXXXY.
49, XXXXY is a rare aneuploidy and variant of Klinefelter syndrome, occurring in 1 per 80,000-100,000 live births. We present a cohort of 40 affected males, focusing on musculoskeletal problems. Subjects were participants in an annual 49er family support group meeting. Children were examined in a multidisciplinary clinic by a pediatric neurologist and geneticist, a pediatric orthopedist, a neurodevelopmentalist, and two physical therapists. The patient data were collected from this clinic from 2004 to 2012. All patients were required to have karyotypes that confirmed the presence of XXXXY. There was a high prevalence of musculoskeletal disorders, particularly hypotonia (34 patients [85%]), radioulnar synostosis (30 [75%]), pes planus (26 [65%]), asymmetric hip rotation (27 [67.5%]), and clinodactyly (24 [60%]). Other, less common lower-extremity disorders, included, 5 patients (12.5%) with unilateral club foot, 5 boys (12.5%) with pes cavus, 10 patients (25%) genu valgum and 2 children with genu varus (5%). To our knowledge, this is the first large cohort of boys with 49, XXXXY that focuses on musculoskeletal disorders. There was an increased incidence of hypotonia, clubfoot, avascular necrosis of the femoral head, radioulnar synostosis, and pes planus compared to the normative population. Boys with 49, XXXXY would benefit from multidisciplinary evaluations, particularly from pediatric orthopedists, physical therapists, neurologists, and geneticists for appropriate medical care.


One-step fabrication of crystalline metal nanostructures by direct nanoimprinting below melting temperatures.
Controlled fabrication of metallic nanostructures plays a central role in much of modern science and technology, because changing the dimensions of a nanocrystal enables tailoring of its mechanical, electronic, optical, catalytic and antibacterial properties. Here we show direct superplastic nanoimprinting (SPNI) of crystalline metals well below their melting temperatures, generating ordered nanowire arrays with aspect ratios up to ∼2,000 and imprinting features as small as 8 nm. Surface-enhanced Raman scattering (SERS) spectra reveal strongly enhanced electromagnetic signals from the prepared nanorod arrays with sizes up to ∼100 nm, which indicates that our technique can provide an ideal way to fabricate robust SERS substrates. SPNI, as a one-step, controlled and reproducible nanofabrication method, could facilitate the applications of metal nanostructures in bio-sensing, diagnostic imaging, catalysis, food industry and environmental conservation.


A resource-saving collective approach to biomedical semantic role labeling.
Biomedical semantic role labeling (BioSRL) is a natural language processing technique that identifies the semantic roles of the words or phrases in sentences describing biological processes and expresses them as predicate-argument structures (PAS's). Currently, a major problem of BioSRL is that most systems label every node in a full parse tree independently; however, some nodes always exhibit dependency. In general SRL, collective approaches based on the Markov logic network (MLN) model have been successful in dealing with this problem. However, in BioSRL such an approach has not been attempted because it would require more training data to recognize the more specialized and diverse terms found in biomedical literature, increasing training time and computational complexity. We first constructed a collective BioSRL system based on MLN. This system, called collective BIOSMILE (CBIOSMILE), is trained on the BioProp corpus. To reduce the resources used in BioSRL training, we employ a tree-pruning filter to remove unlikely nodes from the parse tree and four argument candidate identifiers to retain candidate nodes in the tree. Nodes not recognized by any candidate identifier are discarded. The pruned annotated parse trees are used to train a resource-saving MLN-based system, which is referred to as resource-saving collective BIOSMILE (RCBIOSMILE). Our experimental results show that our proposed CBIOSMILE system outperforms BIOSMILE, which is the top BioSRL system. Furthermore, our proposed RCBIOSMILE maintains the same level of accuracy as CBIOSMILE using 92% less memory and 57% less training time. This greatly improved efficiency makes RCBIOSMILE potentially suitable for training on much larger BioSRL corpora over more biomedical domains. Compared to real-world biomedical corpora, BioProp is relatively small, containing only 445 MEDLINE abstracts and 30 event triggers. It is not large enough for practical applications, such as pathway construction. We consider it of primary importance to pursue SRL training on large corpora in the future.


The retroperitoneal approach for contemporary open abdominal aortic aneurysm surgery: The anatomical reasoning.
In current practice, the place of open surgery in managing abdominal aortic aneurysm is a contentious issue. The principal reason being greater applications of endovascular techniques treating increasingly complicated aortic disease. Development of branched and fenestrated devices enabled this, with numbers increasing annually. This meant a good risk patient with a long infrarenal aortic neck and normal diameter non-tortuous iliac arteries may be suitable for both endovascular and open techniques. However, indications for open surgery are becoming increasingly unclear nowadays due to short-term gains in morbidity and mortality. Exact aortic anatomical morphologies optimum for open or endovascular techniques remains unclear. As graft technology evolves, possibilities for endovascular options are expanding. Currently, establishing optimum treatment plans for complicated abdominal aortic aneurysm (little or no infrarenal neck) is difficult without considering general fitness of the patient. Hence, two sets of possible postoperative complications and follow-up protocols must be explained to patients before either approach. Complicating matters is the optimum surgical approach used for any open repair. The standard approach for open abdominal aortic aneurysm surgery has been transperitoneal as this provides excellent access to the infrarenal aorta and iliac arteries. However, although less commonly used, the retroperitoneal approach has advantages particularly when location of proximal aortic disease indicates suprarenal clamp might be optimum. This paper scrutinises benefits of the retroperitoneal approach performed purely for anatomical reasons where stent graft may be considered complicated. Also, long-term outcomes are examined in terms of endo-leak and subsequent development of true and false aneurysm following both endovascular and open repair.


The effect of nucleotomy and the dependence of degeneration of human intervertebral disc strain in axial compression.
Biomechanics of human intervertebral discs before and after nucleotomy. To noninvasively quantify the effect of nucleotomy on internal strains under axial compression in flexion, neutral, and extension positions, and to determine whether the change in strains depended on degeneration. Herniation and nucleotomy may accelerate the progression of disc degeneration. Removal of nucleus pulposus (NP) tissue has resulted in altered disc mechanics in vitro, including a decrease in internal pressure and an increase in the deformations at physiologically relevant strains. We recently presented a technique to quantify internal disc strains using magnetic resonance imaging (MRI). Degeneration was quantitatively assessed by the T1ρ relaxation time in the NP. Samples were prepared from human levels L3-L4 and/or L4-L5. A 1000-N compressive load was applied while in the magnetic resonance scanner. Nucleotomy was performed by removing 2 g of NP through the posterior-lateral annulus fibrosus (AF). The discs were rehydrated, reimaged, and retested. The analyzed parameters include axial deformation, AF radial bulge, and strains. RESULTS.: The axial deformation was more compressive after nucleotomy. In the neutral position, the axial deformation after nucleotomy correlated with degeneration (as quantified by T1ρ in the NP), with minimal alteration in nondegenerated discs. Nucleotomy altered the radial displacements and strains in the neutral position, such that the inner AF radial bulge decreased and the radial strains were more tensile in the lateral AF and less tensile in the posterior AF. In the bending loading positions the radial strains were not affected by nucleotomy. Nucleotomy alters the internal radial and axial AF strains in the neutral position, which may leave the AF vulnerable to damage and microfractures. In bending, the effects of nucleotomy were minimal, likely due to more of the applied load being directed over the AF. Some of the nucleotomy effects are modulated by degeneration, where the mechanical effect of nucleotomy was magnified in degenerated discs and may further induce mechanical damage and degeneration.


Competing roles of TGFbeta and Nma/BAMBI in odontoblasts.
Nma/BAMBI is a novel pseudoreceptor with homology to a TGFbeta type I receptor that lacks a serine/threonine kinase domain. Nma/BAMBI functions as a dominant-negative protein that regulates reciprocal epithelial-mesenchymal interactions during organogenesis. Therefore, we hypothesized that Nma/BAMBI regulates TGFbeta signaling and downstream gene expression during dentinogenesis. To test this hypothesis, we examined the downstream gene expression profiles of major dentin extracellular matrix proteins in response to Nma/BAMBI, and we examined the roles of Nma/BAMBI and TGFbeta-1 during dentinogenesis. Overexpression of Nma/BAMBI in the mouse odontoblast-like cell line MD10-A2 down-regulated expression of DSPP by 66% and up-regulated expression of DMP1 four-fold. TGFbeta treatment reversed Nma/BAMBI's negative effect on DSPP expression. Furthermore, we demonstrated that TGFbeta negatively regulates Nma/BAMBI's expression levels in MD10-A2 odontoblast-like cells. Analysis of these data, together, indicates that TGFbeta and Nma/BAMBI are inversely regulated and that the sequence of expression determines the net effect on downstream gene expression.


[Genetic and correlation analysis for agronomic traits in flue-cured tobacco (Nicotiana tabacum L.)].
By using a genetic model including additive and dominance effects and their interaction with environments, 7 agronomic traits were analyzed for a diallel design in 4 environmental conditions with 14 flue-cured tobacco varieties (or breeding lines) and their 41 F1 crosses. It was revealed that additive effects were the major genetic component for plant height, internode length, and width of leaves. Number of leaves and length of leaves were mainly controlled by dominance x environment interaction effects. Additive x environment interaction effects and dominance x environment interaction effects played a major role for girth of stem. Yield performance was mainly controlled by additive effects and dominance x environment interaction effects. The varieties adapted to local environments tended to have highly positive additive effects. Dominance effects and the dominance x environment interaction effects could perform differently in positive or negative direction for many crosses. The breeding program for hybrids should consider the adaptation of hybrids to specific ecological environments. The analysis of correlation among agronomic traits indicated that most of phenotypic, genotypic, additive and dominance correlation coefficients were positive. Additive correlations were predominance in genetic correlations for most pairs of traits. Yield can be improved by indirect selection on plant height.


Effect of Fagonia Arabica (Dhamasa) on in vitro thrombolysis.
Atherothrombotic diseases such as myocardial or cerebral infarction are serious consequences of the thrombus formed in blood vessels. Thrombolytic agents are used to dissolve the already formed clots in the blood vessels; however, these drugs have certain limitations which cause serious and sometimes fatal consequences. Herbal preparations have been used since ancient times for the treatment of several diseases. Herbs and their components possessing antithrombotic activity have been reported before; however, herbs that could be used for thrombolysis has not been reported so far. This study's aim was to investigate whether herbal preparations (aqueous extract) possess thrombolytic activity or not. An in vitro thrombolytic model was used to check the clot lysis effect of six aqueous herbal extracts viz., Tinospora cordifolia, Rubia cordifolia, Hemidesmus indicus, Glycyrrhiza glabra Linn, Fagonia Arabica and Bacopa monnieri Linn along with Streptokinase as a positive control and water as a negative control. Using an in vitro thrombolytic model, Tinospora cordifolia, Rubia cordifolia, Hemidesmus indicus, Glycyrrhiza glabra Linn, Fagonia Arabica and Bacopa monnieri Linn showed 19.3%, 14.5%, 20.3%, 17.8%, 75.6% and 41.8% clot lysis respectively . Among the herbs studied Fagonia arabica showed significant % of clot lysis (75.6%) with reference to Streptokinase (86.2%). Through our study it was found that Dhamasa possesses thrombolytic properties that could lyse blood clots in vitro; however, in vivo clot dissolving properties and active component(s) of Dhamasa for clot lysis are yet to be discovered. Once found Dhamasa could be incorporated as a thrombolytic agent for the improvement of patients suffering from Atherothrombotic diseases.


Effects of indigo carmine on human chondrocytes in vitro.
Joint infections following or accompanying superficious soft tissue infections are severe complication in orthopedic surgery. The use of intra-articular blue staining is a helpful method to visualize a fistula and to differentiate between superficial and intra-articular infections. Regarding this clinical implication data about the effects of indigo carmine, a frequently used blue staining substance, on cartilage is missing. The hypothesis of this study was that indigo carmine damages human chondrocytes in a time and concentration dependent manner. Human chondrocytes were isolated from donors with osteoarthritis who were treated with TKA. Cells were cultivated and treated with different concentrations of indigo carmine for 5 and 10 minutes. Morphologic damage was examined by light microscopy. Toxicity was quantified by counting vital cell number and lactate dehydrogenase (LDH) expression. Analysis by light microscopy showed defected cell structure and loss of cell number after treatment with 100% indigo carmine for 10 minutes. Treatment with 10% and 1% indigo carmine showed no significant cell defects and loss of cells. Counting vital cell number showed loss of vital cells after treatment with 100% and 10% indigo carmine for 10 minutes. LDH expression was significantly increased after treatment with 100% indigo carmine.Toxic effects were shown after treatment with indigo carmine. Therefore, it should be used in 1:100 dilution. This is both, sufficient for visualizing a fistula in a possible clinical application and could be protective for chondrocytes.


Metformin effects on clomifene-induced ovulation in the polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a common, complex endocrine disorder for women on reproductive age. A high incidence of ovulation failure is observed in PCO women and perhaps linked to insulin resistance related to metabolic features In the last few years some studies assessed hyperinsulinimea and insulin resistance attenuation effects, by insulin sensitizing agents such as metformin, in PCOS women suggesting potential scope for these drugs in CC ovulation induction quality improvement. Our prospective study aim is to compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. From February 24 to September 29 (2007), PCOS was explored on women attending the Department of Obstetrics & Gynaecology sterility consultation unit (CHU Hedi Chaker-Sfax) according to the Rotterdam 2003 diagnostic criteria. PCOS patients were randomized to receive, in addition to clomifene citrate treatment, placebo or metformin 850 mg two times a day all ovulatory cycle for three trials maximum. Ovulation detection was done by the E2 serum measurements and ovarian transvaginal ultrasonography' evolution controlling on 7th, 11th and 13th day of the cycle. Within 7 months, 32 PCOS women were recruited in the study and equally allocated to the two groups. Baseline characteristics were similar in metformin group and placebo one. Ovulation was characterized by the presence of at least one mature follicle (> 16 mm), a circulating estradiol concentration in the edge of 150-250 pg and accessory an endometrial depth > 8 mm. The ovulation rate in the metformin group was 62.5% compared with 37.5% in the placebo group, a non-statistically significant (small study population) but important difference (1.66 times). Analyses show a higher mature follicle number and estradiol concentration in metformin group than in the placebo one. Metformin effect was, in our study, his only insulinosensitizer property consequence far away a 'making thinner' or Hyperandrogenism reducing ones. The ovulatory response to clomifene can be increased in polycystic ovary syndrome women by decreasing insulin secretion with metformin.


Study of the populations of the Balearic Islands (Spain) using mtDNA RFLPs.
The Balearic archipelago (Spain) is composed of three major islands, Majorca, Minorca, and Ibiza. Majorca is the largest and most populous island. Minorca is the second largest in area and third in population, and Ibiza is the smallest of the three and has the second largest population. Ibiza also shows differences from the other two islands in its landscape, vegetation, and especially origins of the founding settlements. The three islands also have been settled by people of different cultures. We have carried out a genetic analysis at the level of mtDNA RFLPs in these populations and found that the three populations are genetically structured, with differences in the RFLP haplotype frequencies reflecting the different population substrata of the three islands. In this structure Ibiza is genetically more different from Majorca and Minorca. In addition, we found a new haplotype in Minorca, named haplotype 150, which seems to originate from haplotype 56.


Correlative microscopy.
In recent years correlative microscopy, combining the power and advantages of different imaging system, e.g., light, electrons, X-ray, NMR, etc., has become an important tool for biomedical research. Among all the possible combinations of techniques, light and electron microscopy, have made an especially big step forward and are being implemented in more and more research labs. Electron microscopy profits from the high spatial resolution, the direct recognition of the cellular ultrastructure and identification of the organelles. It, however, has two severe limitations: the restricted field of view and the fact that no live imaging can be done. On the other hand light microscopy has the advantage of live imaging, following a fluorescently tagged molecule in real time and at lower magnifications the large field of view facilitates the identification and location of sparse individual cells in a large context, e.g., tissue. The combination of these two imaging techniques appears to be a valuable approach to dissect biological events at a submicrometer level. Light microscopy can be used to follow a labelled protein of interest, or a visible organelle such as mitochondria, in time, then the sample is fixed and the exactly same region is investigated by electron microscopy. The time resolution is dependent on the speed of penetration and fixation when chemical fixatives are used and on the reaction time of the operator for cryo-fixation. Light microscopy can also be used to identify cells of interest, e.g., a special cell type in tissue or cells that have been modified by either transfections or RNAi, in a large population of non-modified cells. A further application is to find fluorescence labels in cells on a large section to reduce searching time in the electron microscope. Multiple fluorescence labelling of a series of sections can be correlated with the ultrastructure of the individual sections to get 3D information of the distribution of the marked proteins: array tomography. More and more efforts are put in either converting a fluorescence label into an electron dense product or preserving the fluorescence throughout preparation for the electron microscopy. Here, we will review successful protocols and where possible try to extract common features to better understand the importance of the individual steps in the preparation. Further the new instruments and software, intended to ease correlative light and electron microscopy, are discussed. Last but not least we will detail the approach we have chosen for correlative microscopy.


Regional attitudes of generalists, specialists, and subspecialists about management of atrial fibrillation.
It is unknown whether physicians' attitudes about the management of atrial fibrillation (AF) reflect the recommendations of published guidelines. To obtain information about physicians' attitudes about management of AF, a questionnaire was returned by 904 (20.1%) of 4500 physicians involved in managing AF (385 cardiologists, 326 internists, and 193 electrophysiologists). The cardiologists and internists were from Massachusetts or California; the electrophysiologists were from around the United States. The questionnaire called for 86 separate answers about use of resources and drug therapy for different types of AF, including recent-onset AF, paroxysmal AF, and chronic AF of less than 6 months' and more than 3 years' duration. Transthoracic echocardiography and thyroid function were requested by more than 90% of physicians; transesophageal echocardiography and catheterization were requested by 10% of physicians. To control ventricular response, digoxin was the overwhelming first-line therapy; calcium channel blockers were favored over beta-blockers for adjunct therapy. To prevent thromboemboli, warfarin sodium was preferred for chronic AF; warfarin or aspirin were equally considered for paroxysmal AF. In considering sinus rhythm, respondents agreed about factors determining whether to revert, the number of drug trials, and the first-line drug choice (quinidine sulfate) but disagreed about second-line antiarrhythmic drugs and whether to hospitalize the patient before initiating drug therapy. Physicians ranging from primary care providers to subspecialists agree on issues of AF management such as heart rate control and anticoagulation. Attitudes vary widely about issues such as antiarrhythmic drugs.


Cannabis Use among Persons with Dementia and Their Caregivers: Lighting up an Emerging Issue for Clinical Gerontologists.
Objectives: Our goal is to illuminate cannabis use among persons with dementia (PwD) and their informal caregivers relative to the use of evidence-based as well as other complementary and alternative care practices. Methods: We analyzed focus group (FG) narratives provided by 26 caregivers of PwD and identified five themes concerning the provision of cannabis to PwD and caregivers' self-use. Results: Three of the 26 caregivers provided PwD cannabis and also used themselves, another 3 of the 26 used themselves only, and all but two of the remaining FG participants indicated they would consider providing cannabis to PwD or using for themselves. These caregivers expressed a desire to obtain more empirically-based information about cannabis and to discuss options with their clinical care providers. Conclusions: A small but significant proportion of caregivers are providing cannabis to PwD as a possible treatment for agitation, sleep disturbances and other problematic secondary symptoms and using for themselves as way to relieve stress. Many other caregivers may start using cannabis upon receiving information and guidance from a credible source. Clinical Implications: Notwithstanding the need for more research, clinical gerontologists and other dementia care specialists are being looked upon to provide information and guidance about the benefits and harms of cannabis use among PwD and their caregivers.


Retinoic acid changes the proximodistal developmental competence and affinity of distal cells in the developing chick limb bud.
In the developing chick limb bud, retinoic acid (RA) has a striking effect on anteroposterior axis formation, resulting in a duplicated pattern of digits. There is no evidence, however, that RA affects proximodistal axis formation in the developing chick limb bud, although RA induces proximodistal duplication in regenerating amphibian limbs. We describe a series of investigations on the effect of RA on the proximodistal axis in the chick limb bud. A RA-containing bead applied to the anterior margin of the chick limb bud at stage 20 induces the anteroposterior duplication of autopodial structures at the wrist level. We found that the RA-treated tissue has the ability to form more proximal structures. When a tissue graft from the RA-treated anterior region was implanted into a stage 17 wing bud (in which the stylopod is developing in the progress zone), the graft produced a humerus, radius-ulna, and digits. When the graft was implanted into a stage 19 wing bud (in which the zeugopod is developing in the progress zone), a zeugopod and digits were formed. These results were associated with changes in the expression of Hox-A genes in the RA-treated grafts, whose domains were reorganized to be similar to those in host tissues 24 h after grafting. When a small graft of RA-treated tissue was implanted into the apex of a stage 19 wing bud, the cells were found in the zeugopod and autopod, whereas cells of control fragments were found only in the autopod region. In vitro, distal cells from different stage limb buds are known to segregate from each other. However, RA-treated stage 24 distal cells did not sort out from stage 20 distal cells and mixed homogeneously. These results suggest that RA induces distal cells to adopt "younger" properties which render them susceptible to forming more proximal patterns under the direction of host signals. The effects of RA on proximodistal patterns in developing chick limb buds appear to differ from its effects on proximodistal patterns in regenerating urodele limbs because RA can induce the proximodistal duplication in situ in the regenerating limbs.


Allergic stomatitis from dental impression compounds.
Two women experienced a severe stomatitis following brief contact with Impregum, a dental impression material. In one patient it was shown that the sensitizer was the catalyst 2,5 dichlorobenzene sulfonate. This dental impression material is widely used in the United States, and has been reported as a sensitizer in Europe. The catalyst in Scutan, another dental impression compound sometimes used instead of the methacrylates, has also been reported in Europe as being a sensitizer.


Facilitators and Barriers Surrounding the Role of Administration in Employee Job Satisfaction in Long-Term Care Facilities: A Systematic Review.
Previous literature has shown how associate engagement has positively impacted on productivity, job satisfaction, safety, retention, consumer sentiment, and financial performance in hospitals and healthcare systems. However, a lack of research showing the relationship between associate engagement and job satisfaction within the long-term care environment has existed. Our objective was to investigate characteristics within the long-term care environment that promote and detract from associate job satisfaction and extrapolate the best practices in maintaining job satisfaction and engagement. This systematic review queried CINAHL, PubMed (MEDLINE), and Academic Search Ultimate databases for peer-reviewed publications for facilitators and barriers commensurate with employee job satisfaction in long-term care facilities using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Kruse Protocols. The authors identified 11 facilitators for job satisfaction and 18 barriers to job satisfaction in the 60 selected articles. The top four facilitators were Supportive Leadership, Capable and Motivated Employees, Positive Organizational Values, and Social Support Mechanisms. The top four barriers were condescending management style, high job demands, lack of self-care, and lack of training with medically complex patients. The systematic review revealed the importance of maintaining satisfied employees in the long-term care workplace through am emphasis leadership and on the facilitators identified to best serve their associates and improve care for residents.


Prenatal Exposure to Cocaine Impairs Neuronal Coding of Attention and Discriminative Learninga.
Cingulate cortex and related areas of the thalamus are critically involved in the mediation of discriminative avoidance learning, wherein rabbits step in response to an acoustic conditional stimulus (CS+) to avoid foot shock and they learn to ignore a different acoustic stimulus (CS-) not followed by shock. Studies of multi-unit neuronal activity recorded simultaneously in many cingulothalamic areas have documented massive learning-related neuronal firing changes during the course of behavioral acquisition. Stimulated by findings (this volume) of neurobiological changes in anterior cingulate cortex in rabbits exposed in utero to cocaine, we investigated behavioral learning and correlated neuronal activity in several cingulothalamic areas in cocaine-exposed rabbits. In an initial study, training-induced enhancement of cingulate cortical neuronal firing in response to the CS+ and CS- was abolished in rabbits exposed to cocaine in utero. Yet discriminative neuronal activity (greater firing in response to the CS+ than to the CS-) did develop during training, and behavioral learning was normal in the cocaine-exposed rabbits. In a second study, we reduced the salience of the CS+ and CS- by employing 200 msec CSs rather than standard 500 msec CSs. Early training-stage development of anterior cingulate cortical discriminative neuronal activity was abolished, the elicited neuronal discharge profiles were altered, and behavioral learning was impaired in rabbits exposed to cocaine, relative to saline-exposed controls. The specificity of these changes to low-salience CSs suggested that prenatal cocaine results in disturbed associative attentional processes of anterior cingulate cortex in adult rabbits. Consideration of the neuronal response profile alterations together with other reported neurobiological changes suggested that the cocaine-related attentional deficit is due to impaired dopaminergic afferent activation of GABA neurons in anterior cingulate cortex.


Allelopathic activity and chemical constituents of walnut (Juglans regia) leaf litter in walnut-winter vegetable agroforestry system.
Walnut agroforestry systems have many ecological and economic benefits when intercropped with cool-season species. However, decomposing leaf litter is one of the main sources of allelochemicals in such systems. In this study, lettuce (Lactuca sativa var. angustata) was grown in the soil incorporated with walnut leaf litter to assess its allelopathic activity. Lettuce growth and physiological processes were inhibited by walnut leaf litter, especially during early growth stage (1-2 euphylla period) or with large amount of litter addition. The plants treated by small amount of leaf litter recovered their growth afterwards, while the inhibition for 180 g leaf litter persisted until harvest. Twenty-eight compounds were identified in the leaf litter, and several of them were reported to be phytotoxic, which may be responsible for the stress induced by walnut leaf litter. Thus, for highest economic value of vegetables such as lettuce, excessive incorporation of leaf litter should be discouraged.


Now we need a framework for action.
Over the past decade, there has been growing policy interest in the role of primary care within the Canadian health system, with the recognition that it has not been fully integrated and that its full potential has not been developed. The framework of Kates et al. starts to address some key organizational issues, by placing the patient, family and community at the centre of the healthcare system and by combining the Institute for Healthcare Improvement's Triple Aim approach with the Institute of Medicine's six improvement aims. What this framework does not do is provide a model of how to organize or deliver primary care or demonstrate how policy makers and those responsible for designing the healthcare system should structure organizational models, payment systems or accountability structures. Kates et al. have provided a useful first step. We now require a commitment to act.


The role of face flies in an episode of infectious bovine keratoconjunctivitis.
Cattle partially protected from face flies (Musca autumnalis) had much less infectious bovine keratoconjunctivitis and yielded fewer isolated of hemolytic Moraxella bovis than did similar cattle that received no face fly protection. The number of new isolated of M bovis from the unprotected cattle was highly correlated with the number of face files observed on the cattle. Close physical proximity to cattle infected with M bovis was important in the spread of the bacteria to previously uninfected cattle; however, it did not require physical contact among the cattle to spread from herd to herd. Moraxella bovis first began to spread from herd to herd after face fly populations exceeded 10/animal for 1 month. Keratoconjunctivitis was not observed in 53% of the cattle from which M bovis was isolated. Moraxella bovis was isolated from 4 of 45 pools of face files collected from animals in the untreated herds.


The intraoperative effect of pentoxifylline on the inflammatory process and leukocytes in cardiac surgery patients undergoing cardiopulmonary bypass.
Inflammation plays a pivotal role in the pathogenesis of organ dysfunction after cardiopulmonary bypass (CPB). The aim of this study was to investigate whether pentoxifylline (PTX) has effects on the inflammatory process and leukocytes in cardiac surgery patients undergoing CPB. A double-blind, prospective, randomized, placebo-controlled study was undertaken to assess the effect of PTX on leukocyte counts, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) levels in 60 patients undergoing CPB for elective coronary artery bypass grafting. In 30 patients, 200 mg of PTX was added to 500 mL NaCl and perfused for 180 min after induction of anaesthesia and also 100 mg of PTX was added to the warm cardioplegic solution; another 30 patients received saline solution as placebo. All measurements were performed before PTX infusion (T0), after induction of anaesthesia (T1), 30 min after weaning from CPB (T2), and 6 hours (T3) and 24 hours postoperatively (T4). PTX did not change the percentage of eosinophils, basophils, neutrophils, monocytes, or lymphocytes, or CRP levels. In the control group, however, total leukocyte count and IL-6 level at T3 and T4 period were significantly higher than the study group. The progressive increment in TNF-alpha level observed at each period was also significantly prominent in the control group. CPB-related whole body inflammatory response could be partially inhibited by intraoperative PTX administration. This effect of PTX would be helpful in preventing the well-known complications of CPB-induced systemic inflammation.


Cassava Witches' Broom Disease in Southeast Asia: A Review of Its Distribution and Associated Symptoms.
Cassava witches' broom disease (CWBD) is one of the main diseases of cassava in Southeast Asia (SEA). Affected cassava plants show reduced internodal length and proliferation of leaves (phyllody) in the middle and top part of the plant, which results in reduced root yields of 50% or more. It is thought to be caused by phytoplasma; however, despite its widespread distribution in SEA still little is known about CWBD pathology. The overarching goal of this study was to review and corroborate published information on CWBD biology and epidemiology considering recent field observations. We report the following: (1) CWBD symptoms are conserved and persistent in SEA and are distinct from what has been reported as witches' broom in Argentina and Brazil. (2) In comparison with cassava mosaic disease, another major disease of cassava in SEA, symptoms of CWBD develop later. (3) Phytoplasma detected in CWBD-affected plants belong to different ribosomal groups and there is no association study available indicating phytoplasma as the causing agent of CWBD. These findings are essential clues for designing surveillance and management strategies and for future studies to better understand the biology, tissue localization and spatial spread of CWBD in SEA and other potential risk areas.