Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort.
This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort. The magnitude of association for each genotype was assessed in 1,046 RA subjects from the Yorkshire Early RA cohort and in 5,968 healthy UK controls. Additional exploratory subanalyses were undertaken in subgroups defined by autoantibody status (rheumatoid factor and anti-cyclic citrullinated peptide) or disease severity (baseline articular erosions, Health Assessment Questionnaire (HAQ) score and swollen joint count (SJC)). In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA. The magnitude of association for these loci was increased in those patients who were autoantibody-positive. PTPN22 was associated with autoantibody-negative RA (per-allele OR = 1.3, trend P = 0.04). There was no evidence of association between these five genetic loci and baseline erosions or SJC in the total RA cohort, after adjustment for symptom duration. TRAF1/C5 was significantly associated with baseline HAQ, however, following adjustment for symptom duration (P trend = 0.03). These findings support the mounting evidence that different genetic loci are associated with autoantibody-positive and autoantibody-negative RA, possibly suggesting that many of the genes identified to date are associated with autoantibody production. Additional studies with a specific focus on autoantibody-negative RA will be needed to identify the genes predisposing to this RA subgroup. The TRAF1/C5 locus in particular warrants further investigation in RA as a potential disease severity locus.


[Treatment of atypical post-traumatic and postoperative facial neuralgias by chronic stimulation. Apropos of 2 cases, with review of the literature].
This article describes the case of two patients suffering from deafferentation pain after surgery or traumatic lesions in the area of the peripheric trigeminal branches on the Gasserian ganglion. Chronic electrical stimulation by an electrode implanted in the Gasserian ganglion led to a good permanent result in both cases, within a follow-up period of one year and one year and a half, respectively. The pre-operative test was carried out percutaneously via the foramen ovale, the definitive implantation by surgery with subtemporal access. This method can only be used when at least part of the ganglion cells of the Gasserian ganglion are intact. According to identical observations by other authors, it is mostly adequate for surgical and traumatic trigeminal lesions, whereas for pain due to herpes zoster, the stimulation of specific thalamus nuclei is a much better method.


Symptomatic Os Navicular on 99mTc-MDP SPECT/CT.
Os navicular bone is an accessory bone of the foot, which is mainly found on the medial side of the proximal navicular bone. Os navicular bone may be symptomatic and cause medial foot pain. We report a case of a 42-year-old athlete male having right foot pain diagnosed with os navicular syndrome on 99mTc-MDP bone scintigraphy SPECT/CT. We emphasize on the use of SPECT/CT in not only allocating the ossicle anatomically, but also for the purpose of evaluating an active source of pain in a region of multiple complex small bones.


[A rare cause of febrile cervical pain].
Febrile cervical pain is often secondary to meningitis or spondylodiscitis and, exceptionally, to microcrystalline arthropathy. We here report a case. A 81-year old man with no particular personal history was hospitalized with febrile cervical pain. Initial diagnoses were meningitis and spondylodiscitis. Clinical examination showed overall stiffness of cervical rachis. Spinal MRI showed abnormality of the atlanto-axial articulation signal, enhanced after gadolinium injection with synovial hypertrophy associated with irregular and heterogeneous aspect of the dens of the axis. Serial atlanto-axial Computed Tomography (CT) scan showed peri-odontoid calcifications, confirming the diagnosis of crowned dens syndrome (CDS). Patient evolution was favorable under nonsteroidal anti-inflammatory drugs (NSAIDs). CDS deserves to be better known; it can mimic many disorders and be responsible for long term fever.


Antithrombotic therapy in patients with known risk factors for thromboembolism.
In about 50% of the cases of spontaneous deep vein thrombosis a congenital deficiency of an inhibitor of coagulation or an insufficient fibrinolytic mechanism can be detected. In arterial thromboembolism a connection with hyperactive platelets or with a diminished availability of tissue plasminogen activator can be found in about 70%. However, in these cases the defect which provokes thrombosis is mostly acquired and is connected with hyperlipidemia and/or with atherosclerotic alterations of the vessel wall. A study on patients with thromboembolic tendency and detectable risk factors was carried out. A total of 470 patients could be observed for 2 years under an adequate antithrombotic prophylaxis. The occurrence of thromboembolic episodes 2 years prior to prophylaxis and 2 years under prophylaxis was compared. In venous cases thrombosis could be controlled almost completely by coumarins when the underlying cause was a deficient plasmatic inhibitor. In patients with diminished fibrinolysis there was only a partial effect of oral anticoagulants. A better result could be obtained when pentosan polysulfate was administered. In arterial thromboembolism the results of prophylaxis were less convincing. The efficacy of ASA in patients with an increased platelet function was only moderate. In addition, ASA hat to be discontinued in about 20% of the patients because of gastrointestinal problems. Pentosan polysulfate in patients with a diminished fibrinolytic capacity had a fairly good effect and resulted in a 60% reduction of thromboembolic manifestations. It is shown that an exact diagnosis of the underlying deficiency which is likely to cause thrombosis can also improve the efficacy and the specificity of prophylaxis.


Mucosal drug delivery: membranes, methodologies, and applications.
In recent years, extensive research into novel forms of drug delivery has suggested that mucosal approaches offer a promising therapeutic alternative, especially for systemically acting drugs. Transmucosal drug delivery offers many benefits, including noninvasive administration, convenience, rapid onset, as well as elimination of hepatic first-pass metabolism. The investigated absorptive surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among these, the nasal and buccal routes have proved the most promising to date. The bioavailability achieved mainly depends upon the pathophysiological state of the mucosa and the properties of both the drug and delivery systems. Various agents can increase the efficacy of transmucosal drug delivery. These include cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres, liposomes, and bioadhesive agents. The mechanisms of action, effectiveness, and toxicity profiles of these enhancers have been investigated extensively in both animal and human models.


Spherical hashing: binary code embedding with hyperspheres.
Many binary code embedding schemes have been actively studied recently, since they can provide efficient similarity search, and compact data representations suitable for handling large scale image databases. Existing binary code embedding techniques encode high-dimensional data by using hyperplane-based hashing functions. In this paper we propose a novel hypersphere-based hashing function, spherical hashing, to map more spatially coherent data points into a binary code compared to hyperplane-based hashing functions. We also propose a new binary code distance function, spherical Hamming distance, tailored for our hypersphere-based binary coding scheme, and design an efficient iterative optimization process to achieve both balanced partitioning for each hash function and independence between hashing functions. Furthermore, we generalize spherical hashing to support various similarity measures defined by kernel functions. Our extensive experiments show that our spherical hashing technique significantly outperforms state-of-the-art techniques based on hyperplanes across various benchmarks with sizes ranging from one to 75 million of GIST, BoW and VLAD descriptors. The performance gains are consistent and large, up to 100 percent improvements over the second best method among tested methods. These results confirm the unique merits of using hyperspheres to encode proximity regions in high-dimensional spaces. Finally, our method is intuitive and easy to implement.


Underlying mechanism of combined effect of methamphetamine and morphine on lethality in mice and therapeutic potential of cooling.
An increase in polydrug abuse is a major problem worldwide. A previous study showed that coadministration of methamphetamine and morphine induced lethality in rodents and humans. However, the underlying mechanisms by which the lethality is increased by the coadministration of methamphetamine and morphine have not been fully understood. Therefore, the present study was designed to determine the mechanism of increased lethality induced by methamphetamine and morphine. Coadministered methamphetamine and morphine increased the lethality by more than 70% in BALB/c mice. Pretreatment with NMDA-receptor antagonists, such as MK-801 and 3-((R)-2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP), and benzamide [poly(ADP-ribose) polymerase (PARP) inhibitor] significantly attenuated the increased lethality induced by methamphetamine and morphine. Furthermore, the lethal effect induced by methamphetamine and morphine was completely attenuated by immediate cooling after the coadministration of methamphetamine and morphine. It has been reported that methamphetamine-induced neurotoxicity can be blocked by lowering the temperature, and this effect might be mediated by a reduction of release of free radicals. These results suggest that activation of NMDA receptors and PARP play an important role in the increased lethality induced by methamphetamine and morphine.


Atrial autonomic innervation remodelling and atrial fibrillation inducibility after epicardial ganglionic plexi ablation.
The effects of ganglionated plexi (GP) ablation on atrial fibrillation (AF) inducibility and atrial autonomic innervation remodelling have not been elucidated. Thirteen dogs were randomly divided into sham-operated group and GP ablation group. All animals underwent a right thoracotomy at the fourth intercostal space. Atrial fibrillation inducibility was assessed by burst rapid pacing at right atrium (RA). After anterior right GP and inferior right GP ablation, AF inducibility was assessed in the GP ablation group. The animals were allowed to recover for 8 weeks, after which, AF was measured again. The levels of atrial natriuretic peptide (ANP) in blood and atrial tissues were examined by radioimmunoassay. Immunocytochemical staining of cardiac nerves was performed in tissues from the dogs. Atrial fibrillation was induced easily in the GP ablation group after 8 weeks although AF was not observed in the sham-operated group, and after instant GP ablation. Compared with that in the sham-operated group, the levels of ANP in the blood and RA increased significantly 8 weeks after GP ablation (111.4 +/- 18.2 vs. 175.1 +/- 25.9; 184.9 +/- 36.3 vs. 299.1 +/- 32.5; P < 0.05). In the GP ablation group, the density of growth-associated protein 43-positive, tyrosine hydroxylase-positive, and choline acetyltransferase-positive nerves in the RA was 821 +/- 752, 481 +/- 627, and 629 +/- 644 per mm(2), respectively, which was significantly (P < 0.01) lower than the nerve density in sham-operated tissues (2590 +/- 841, 1752 +/- 605, and 3147 +/- 886 per mm(2), respectively). Atrial autonomic innervations remodelling may be the mechanism of induced AF after GP ablation.


mHealth to promote pregnancy and interconception health among African-American women at risk for adverse birth outcomes: a pilot study.
The use of mobile phone applications (mHealth) to provide health education and behavioral prompts is 1 of the 12 common mHealth functions identified by the World Health Organization as innovations to strengthen health systems. Among low-income pregnant and parenting women, health education is widely recognized as a way to improve maternal and infant health outcomes, but the efficacy of written health education materials to change knowledge and behavior for this population is questionable. mHealth prompts, in contrast, is a promising alternative. A team of researchers in medicine/epidemiology, anthropology/midwifery, computer science/sensors, and community-based case management created and pilot tested a mHealth application (mHealth app) for African-American women at high risk for adverse birth outcomes. We tested the acceptability and feasibility of the interactive application among women during the reproductive stages of early and late pregnancy, postpartum, and interconception. Interview data from 14 women in the various reproductive stages revealed that most women found the mHealth messages helpful. Also, 62 Ob-Gyn physicians and nurses and 19 Family Medicine residents provided feedback. Women's responses to specific messages trended down over time. Women in the postpartum phase had the highest response rate to particular text messages, followed by those in the pregnancy phase. Responses dropped off dramatically during the interconception period. About 21% of women lost their phones. Unexpected findings were that all participants already had smartphones, women wanted messages about depression, and clinicians wanted the app to link to case management for individualized medical care. Logistical challenges to app management were limitations but are useful for consideration before scale-up. This study corroborates findings in the health literacy literature that women most at risk for adverse birth outcomes need additional face-to-face support with mHealth applications.


Oxidized low-density lipoprotein increases bone sialoprotein expression in vascular smooth muscle cells via runt-related transcription factor 2.
Vascular calcification is a pivotal stage in atherosclerosis. During vascular calcification, vascular smooth muscle cells (VSMCs) synthesize many osteogenic factors such as bone sialoprotein (BSP). Oxidative stress plays a critical role in progression of atherosclerosis and also increases extracellular matrix proteins expression. BSP overexpression has been observed during vascular calcification by oxidative stress. However, the regulatory mechanism of oxidized low-density lipoprotein (oxLDL)-mediated vascular calcification has not yet been fully defined. In this study, we aimed to investigate whether runt-related transcription factor 2 (Runx2) affects the oxLDL-induced BSP expression or not. In this experimental study, we cultured VSMCs in F12K media and then treated them with oxLDL. The expression of Runx2 and BSP genes was determined by real-time polymerase chain reaction method. Protein level of each gene was investigated by Western blotting technique. To determine whether Runx2 regulates BSP gene expression at VSMCs induced by oxLDL, we suppressed Runx2 mRNA using siRNA. Transfected cells then were treated with oxLDL and expression of Runx2 and BSP genes was determined again. oxLDL increased Runx2 and BSP expression (4.8 ± 0.47-fold and 4.91 ± 0.56-fold, respectively) after 48 hours. Western blotting method confirmed the increased levels of Runx2 and BSP proteins after 48 hours. Runx2 overexpression alone induced BSP expression, whereas knockdown of Runx2 with small interfering siRNA blocked oxLDL-induced BSP expression. Our results showed that oxLDL-induced BSP expression was dependent on Runx2 expression, suggesting that Runx2 is required for oxLDL-induced BSP expression.


Automated ABO Rh-D blood type detection using smartphone imaging for point-of-care medical diagnostics.
We present a novel methodology for automated ABO Rh-D blood typing using simple morphological image processing algorithms to be used in conjunction with a fabric strip based rapid diagnostic test. Images of the fabric strip post testing are acquired using low cost mobile phones and the proposed algorithm proceeds to automatically identify the blood type by processing the images using steps comprising of noise reduction, range filtering and empirically derived heuristics. The ultimate goal is to provide a simple mobile phone application to enable automated, rapid and accessible blood type detection at the point-of-care.


Risky sexual behaviors of adolescents in rural Malawi: evidence from focus groups.
Little is known about rural Malawian adolescents' perceptions of their sexual behavior and what would constitute an effective HIV risk-reduction program. This study explored the perceptions of Malawain adolescents using qualitative description research with focus groups. A purposive sample of 144 adolescents, ranging from 10 to 19 years of age was obtained. Subjects were then placed in focus groups separated by gender Qualitative content analysis revealed that adolescents were at risk for HIV based on the select behaviors These included early sexual debut, multiple partners, non-use of condoms and among girls older partners These adolescents acknowledged peer pressure and lack of parental supervision as factors that perpetuated these behaviors and identified two components of HIV prevention programs. For example, parental involvement and support for sexual abstinence were among the issues discussed. It is essential that HIV risk-reduction programs create ways of involving parents and of enhancing adolescents' HIV risk-reduction skills by helping them to change peer norms and to develop negotiation and assertiveness skills to in order to resist peer pressure.


The Evaluation of Different Treatment Approaches in Patients With Earthquake-Related Crush Syndrome.
On February 6, 2023, an earthquake occurred in Kahramanmaras, Turkey, resulting in loss of life, injuries, and the displacement of thousands of people. The aim of this study is to determine the factors affecting amputation and fasciotomy decisions in patients with crush syndrome, along with clinical laboratory parameters. The study included patients over 18 years of age who presented with crush injuries and exhibited systemic symptoms. Inclusion criteria comprised patients with creatine kinase (CK) levels exceeding 1,000 IU/L, oliguria (urine output less than 400 mL per day), elevated blood urea nitrogen (BUN) levels surpassing 40 mg/dL, serum creatinine exceeding 1.5 mg/dL, potassium levels over 6 mEq/L, phosphorus levels surpassing 8 mg/dL, and serum calcium levels below 8 mg/dL. Multiple parameters were evaluated, including blood glucose, serum sodium, potassium, calcium, phosphorus, BUN, creatinine, uric acid, CK, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, prothrombin time (international normalized ratio (INR)), urinalysis, C-reactive protein (CRP), venous blood gas, ECG, and chest radiography. Following the Maraş earthquake, a total of 3,184 patients were admitted to our hospital within the first seven days. Out of these patients, 2,216 received outpatient treatment, 639 were hospitalized in the general ward, and 128 were admitted to the intensive care unit. Among the admitted patients, 237 were diagnosed with crush syndrome, with 126 being male and 111 being female. The average duration of being trapped under debris was eight hours, ranging from four to 36 hours. In the study population, extremity trauma was observed in 84 patients, thoracic trauma in 32 patients, and abdominal trauma in 20 patients. Erythrocyte replacement was administered to 123 patients, while fresh frozen plasma was given to 69 patients, for a total of 1008 units utilized. Mannitol infusions were provided to 58 patients, while bicarbonate infusions were administered to 116 patients. Among the cohort, 71 patients underwent dialysis, with nine of them receiving hemodialysis along with mannitol. Additionally, 67 patients experienced stage 3 acute kidney injury, and 41 patients were deceased. None of the patients required permanent hemodialysis. Earthquakes are considered to be one of nature's most significant and inevitable disasters. While it is impossible to prevent them, effective management strategies are crucial in mitigating the ensuing chaos and reducing casualties. In order to achieve this, it is imperative to draw lessons from past seismic events and apply appropriate treatment protocols to the affected individuals.


Predictors of poor outcome in patients with neck pain treated by physical therapy.
This study evaluated predictors of poor outcome in patients with neck pain treated by physical therapy, and sought to compare the findings of empirical data with physical therapy practitioners' subjective perceptions about predictors of outcome. This study was a secondary analysis of data from a randomized controlled trial assessing physical therapy treatments for neck pain (n=346). A baseline questionnaire provided data on a number of potential risk factors of poor outcome at follow-up. Follow-up was conducted at 6 weeks and 6 months by postal questionnaire with outcome defined separately by perceived (global) change and minimal clinically important differences in the Northwick Park Neck Pain Questionnaire (MCID-NPQ). Therapists' perceptions of predictors for treatment outcome were captured using a separate questionnaire, and the ratings compared with ranks derived from the 6-month trial data. Baseline characteristics accounted for a much greater proportion of explained variance for global change compared with MCID-NPQ at 6 months. Independent biopsychosocial characteristics included manual social class, catastrophizing, anxiety and depression, low treatment expectations, severity of baseline neck pain/disability, presence of comorbid back pain, and older age. Physical therapist ranks correlated highly with those derived from the trial data. Significant predictors of outcome were identified, particularly at 6 months, including psychosocial, functional, and demographic indicators. Our findings suggest that physical therapists are collectively aware of the relative importance of physical and psychosocial factors in predicting clinical outcome. However, a significant amount of variability in outcomes in our prognostic models remained largely unexplained, indicating that we need to explore further underlying factors to inform clinical decision-making.


[Levels of intracellular IL-6 and IFN-gamma in children with acute lymphoblastic leukemia].
To study the changes of intracellular interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) expressions in children with acute lymphoblastic leukemia (ALL) at different stages, and to examine the correlation between IL-6 and IFN-gamma in ALL children. The levels of intracellular IL-6 and IFN-gamma in venous blood lymphocytes were detected by flow cytometry in 42 children with ALL at diagnosis and at remission stage. Twenty healthy children were used as the controls. The intracellular IL-6 level in ALL children at diagnosis was 81.74+/-9.31, which was much higher than that in the Control group (5.67 +/- 0.96 ) (P < 0.01). The intracellular IFN-gamma level in ALL children (1.31 +/- 0.32) was significantly lower than that in the Control group (1.46 +/- 0.49) (P < 0.01). However, the intracellular IL-6 level (27.52 +/- 3.40) decreased remarkably in ALL patients at remission stage (P < 0.01), but was still higher than that in the Control group (P < 0.01). In contrast, the intracellular IFN-gamma level (1.97 +/- 0.72) increased noticeably in ALL patients at remission stage, which was higher than that at diagnosis and the Control group (P < 0.01). A negative correlation was found between the intracellular IL-6 and the IFN-gamma levels in ALL patients (r=-0.476, P < 0.05). Intracellular IL-6 and IFN-gamma levels may be used as the markers for monitoring the response to treatment in ALL patients. There is a negative correlation between intracellular IL-6 and IFN-gamma levels in ALL children.


Research methods for promotion of lung health.
The goal of health research is to develop new knowledge for action to improve health. Relevant health research includes study of diseases, their causes and their treatment/prevention as well as structure and utilisation of health services and policies to improve lung health. As resources are not infinite, priorities must be established. These are determined by the relative frequency of a condition, how much dysfunction or disability it produces and whether there are cost-effective means to deal with it. Epidemiology is the discipline used to address these issues. Using it, one can describe the distribution and relative importance of a condition (the descriptive study), identify determinants and define its natural history (the analytical study), assess methods of prevention, cure and amelioration (the experimental study) and evaluate the process and outcome of services (health services or operational research). Epidemiology addresses itself to determining causation among associated variables. Characteristics associated with causation include consistency, strength of association, specificity, dose response, temporal relationship, coherence, and experimental evidence. Epidemiology can truly be described as the 'basic science of public health.' When used strategically, it can create the new knowledge that is the cornerstone for improving the health of the whole population.


Multiple system atrophy: insights into a rare and debilitating movement disorder.
Multiple system atrophy (MSA) is a devastating and fatal neurodegenerative disorder. The clinical presentation of this disease is highly variable, with parkinsonism, cerebellar ataxia and autonomic failure being the most common - and often debilitating - symptoms. These symptoms progress rapidly, and patients die from MSA-related complications after 9 years of symptom duration on average. Unfortunately, the course of the disease cannot be improved by drug or surgical treatment. In addition, symptomatic treatment options are currently limited, and therapeutic benefits are often only transient. Thus, further interventional studies of candidate disease-modifying and symptomatic therapies are essential to improve patient care. In the past 15 years, the understanding of MSA-specific requirements in trial methodology has improved, resulting in a substantial increase in high-quality interventional studies. In this Review, we discuss MSA risk factors, clinical presentation and neuropathology, and we provide a hypothesis on key pathophysiological events, a summary of recent randomized controlled trials, and an overview of ongoing international collaborations.


Localization of high affinity [3H]glycine transport sites in the cerebellar cortex.
A study was made of [3H]glycine uptake sites in a preparation greatly enriched in large pieces of the cerebellar glomeruli (glomerulus particles) and in morphologically well preserved slices of rat cerebellum. Electron microscopic autoradiography revealed that of the neurones in the cerebellar cortex only Golgi cells transported [3H]glycine at the low concentration used. Glial cells also took up [3H]glycine but to a lesser extent than the Golgi neurons. It was also confirmed that under comparable conditions Golgi cells transport [3H]GABA. Kinetic studies utilizing the Golgi axon terminal-containing glomerulus particles showed that glycine is a weak non-competitive inhibitor of [3H]GABA uptake (Ki over 600 microM vs the Kt of about 20 microM) and that GABA is an even weaker inhibitor of [3H]glycine uptake. These observations indicated that glycine and GABA do not share the same carrier. Quantitative electron microscopic autoradiography showed that the uptake of the two amino acids, in terms of the unit area of labelled Golgi axon terminals, was not additive. In contrast, their uptake in terms of unit protein was strictly additive. These observations, the first relating to unit volume and the latter to the total volume of Golgi terminals, are consistent with the view that there are two biochemically separate populations of Golgi neurons, one transporting glycine the other GABA. Saturable [3H]strychnine binding was detected in the preparations of glomerulus particles, but in comparison with those from the spinal cord the affinity was lower and [3H]strychnine was not displaced by glycine. Available information on glycine receptors, however, suggest that this should not exclude the possibility of strychnine resistant glycine receptors in the rat cerebellum.


The Split Personality of Beauveria bassiana: Understanding the Molecular Basis of Fungal Parasitism and Mutualism.
Fungal pathogenicity toward insects has independently evolved several times, resulting in specialist and generalist pathogens, some of whom have maintained aspects of their previous lifestyles. Being able to grow as an endophyte (engaging in a mutualistic interaction with plants) or saprophyte (recycling nutrients back into the environment), the generalist (broad-host-range) fungus Beauveria bassiana does not need to rely on insect hosts to complete its life cycle. The diverse lifestyles of this fungus, saprophyte, pathogen, and symbiont, provide a unique system, with available genetic tools, to examine host-pathogen interactions, plant-fungus mutualistic relationships, and fungal development. This commentary highlights overlooked pathogenic and mutualistic aspects of B. bassiana that assist this fungus in shifting along the saprobe/parasite/mutualist continuum. Addressing these knowledge gaps and scrutinizing valuable players driving such a spectrum of ecological interactions will enrich our knowledge of fundamental environmental microbiology and help develop new approaches to pest control and sustainable farming.


[Hydroxylation of androgenic steroids in their target organs].
Enzymatic transformations of androgenic steroids in their target tissues lead to molecules which are androgenically more or less active than testosterone. Among such enzymes, and depending with organs, hydroxylases selectively act upon several androgenic steroids. In testes, the 7 alpha-hydroxylation of biosynthesized testosterone and androstenedione gives molecules implied in the regulation of male hormone production. In prostate, epididymis, sebaceous glands and pituitary, 6 alpha- and 7 alpha-hydroxylations only occur with 5 alpha-reduced and 3 beta-hydroxylated derivatives of 5 alpha-dihydrotestosterone. The cells preferentially dispose of such hydroxylated metabolites, but their formation is decreased by estradiol. The position of hydroxylations in the steroid hormone metabolism of each tissue is shown, and their implication in hormone-dependent pathologic growths are discussed.


Can wide consultation help with setting priorities for large-scale biodiversity monitoring programs?
Climate and other global change phenomena affecting biodiversity require monitoring to track ecosystem changes and guide policy and management actions. Designing a biodiversity monitoring program is a difficult task that requires making decisions that often lack consensus due to budgetary constrains. As monitoring programs require long-term investment, they also require strong and continuing support from all interested parties. As such, stakeholder consultation is key to identify priorities and make sound design decisions that have as much support as possible. Here, we present the results of a consultation conducted to serve as an aid for designing a large-scale biodiversity monitoring program for the province of Québec (Canada). The consultation took the form of a survey with 13 discrete choices involving tradeoffs in respect to design priorities and 10 demographic questions (e.g., age, profession). The survey was sent to thousands of individuals having expected interests and knowledge about biodiversity and was completed by 621 participants. Overall, consensuses were few and it appeared difficult to create a design fulfilling the priorities of the majority. Most participants wanted 1) a monitoring design covering the entire territory and focusing on natural habitats; 2) a focus on species related to ecosystem services, on threatened and on invasive species. The only demographic characteristic that was related to the type of prioritization was the declared level of knowledge in biodiversity (null to high), but even then the influence was quite small.


Medical audit on asthma in an emergency department.
To determine the management of acute bronchial asthma in an adult emergency department. A retrospective medical audit of 46 consecutive adult patients with acute asthma exacerbations was performed. We collected information from 48 episodes of acute asthma over a 5-month period. Using classical audit methodology, four indicators were examined: severity evaluation, diagnostic tests, specific treatment, and discharge treatment plans. The least recorded severity indicators were respiratory rate (27 %), heart rate (50 %) and peak expiratory flow (20 %). Heart and respiratory auscultation were recorded in all patients and oxygen saturation was recorded in 93 %. Laboratory blood test and chest radiograph were performed in all patients. Arterial blood gas was tested in 57 %, electrocardiography in 17 %, and coagulation in 39 %. No treatment was provided in 12 % of patients. Bronchodilator medications were administered in all treated patients and oxygen was prescribed in 60 %. Systemic corticosteroids (methylprednisolone or hydrocortisone) were administered in 80 % of treated patients. Seventeen percent of patients were discharged from hospital with no change to their usual treatment. The following weak points were identified: 1) Severity assessment is inadequate, 2) use of diagnostic tests is excessive, 3) patients discharged to home with no treatment plan. Opportunities for improvement consisted of: 1) greater availability of peak expiratory flow meters, 2) individualized use of diagnostic tests, and 3) management protocols.


Association between the endothelial nitric oxide synthase gene Glu298Asp polymorphism and coronary heart disease: a meta‑analysis of 39 case‑control studies.
Numerous studies have indicated that the human endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism is associated with coronary heart disease (CHD) susceptibility, however, their conclusions are inconsistent. The present meta‑analysis aimed to evaluate the precise result by searching the PubMed database and using 39 case‑control studies comprising 7489 cases and 7051 controls.Each study tested the association between the eNOS Glu298Asp polymorphism and CHD. A meta‑analysis was then conducted using the Comprehensive Meta Analysis 2.2 software to calculate the pooled odds ratios (ORs) of five genetic models with 95% confidence intervals (CIs). Publication bias was also explored. The meta‑analysis showed a significant association between the eNOS Glu298Asp polymorphism and CHD susceptibility for all the genetic models [Asp vs. Glu, OR 1.26, 95% CI 1.14‑1.40, P<0.001; Asp/Asp vs. Glu/Glu, OR 1.58, 95% CI 1.23‑2.02, P<0.001; Glu/Asp vs. Glu/Glu, OR 1.12, 95% CI 1.03‑1.22, P=0.001; (Glu/Asp+Asp/Asp) vs. Glu/Glu, OR 1.17, 95% CI 1.07‑1.27, P<0.001; Asp/Asp vs. (Glu/Glu+Glu/Asp), OR 1.59, 95% CI 1.25‑2.03, P<0.001]. Subgroup and sensitivity analyses indicated that the result was robust. A weak publication bias was detected. The results indicated that the eNOS Glu298Asp polymorphism is a risk factor for developing CHD, particularly in the Asian population.


Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion.
B cells play a central role in antibody-mediated rejection and certain autoimmune diseases. However, B cell-targeted therapy such as anti-CD20 B cell-depleting antibody (aCD20) has yielded mixed results in improving outcomes. In this study, we investigated whether an accelerated B cell reconstitution leading to aCD20 depletion resistance could account for these discrepancies. Using a transplantation model, we found that antigen-independent inflammation, likely through toll-like receptor (TLR) signaling, was sufficient to mitigate B cell depletion. Secondary lymphoid organs had a quicker recovery of B cells when compared to peripheral blood. Inflammation altered the pharmacokinetics (PK) and pharmacodynamics (PD) of aCD20 therapy by shortening drug half-life and accelerating the reconstitution of the peripheral B cell pool by bone marrow-derived B cell precursors. IVIG (intravenous immunoglobulin) coadministration also shortened aCD20 drug half-life and led to accelerated B cell recovery. Repeated aCD20 dosing restored B cell depletion and delayed allograft rejection, especially B cell-dependent, antibody-independent allograft rejection. These data demonstrate the importance of further clinical studies of the PK/PD of monoclonal antibody treatment in inflammatory conditions. The data also highlight the disconnect between B cell depletion on peripheral blood compared to secondary lymphoid organs, the deleterious effect of IVIG when given with aCD20 and the relevance of redosing of aCD20 for effective B cell depletion in alloimmunity.


Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins.
Caveolae are plasmalemmal microdomains that are involved in vesicular trafficking and signal transduction. We have sought to identify novel integral membrane proteins of caveolae. Here we describe the identification and molecular cloning of flotillin. By several independent methods, flotillin behaves as a resident integral membrane protein component of caveolae. Furthermore, we have identified epidermal surface antigen both as a flotillin homologue and as a resident caveolar protein. Significantly, flotillin is a marker for the Triton-insoluble, buoyant membrane fraction in brain, where to date mRNA species for known caveolin gene family members have not been detected.


Z2 topological order and the quantum spin Hall effect.
The quantum spin Hall (QSH) phase is a time reversal invariant electronic state with a bulk electronic band gap that supports the transport of charge and spin in gapless edge states. We show that this phase is associated with a novel Z2 topological invariant, which distinguishes it from an ordinary insulator. The Z2 classification, which is defined for time reversal invariant Hamiltonians, is analogous to the Chern number classification of the quantum Hall effect. We establish the Z2 order of the QSH phase in the two band model of graphene and propose a generalization of the formalism applicable to multiband and interacting systems.


Accelerated conditions for stability assessment of bulk and formulated cefaclor monohydrate.
The stability of cefaclor monohydrate drug substance and formulated products was studied under accelerated conditions in order to provide a rapid indication of differences that might result from a change in manufacturing process or source of the sample. The USP stability-indicating related substances assay was used to assess the extent of sample degradation. An Arrhenius study of drug substance stability from 45 to 70 degrees C predicted a degradation rate consistent with that observed in room-temperature studies. Qualitative degradation profiles of samples held at 65 degrees C for 2 weeks were also very similar to those of samples held at room temperature for 2 years. Based on these results, additional studies were conducted at 65 degrees C for 2 weeks on drug substance and formulated product samples. Stability differences were observed among some capsule formulations that had also exhibited real time differences. In some studies, rapid degradation after 5 days was observed at 65 degrees C followed by a slower rate from 5 to 15 days. Similar behavior was observed for cefaclor monohydrate containing high amounts of amorphous cefaclor, suggesting that differences in amorphous content could be an explanation for stability differences observed in various samples. The accelerated conditions were shown to differentiate samples and can provide a rapid indication of relative stability.


[Change of the erythrocyte chemokine receptor binding activity in scalded rats with Pseudomonas aeruginosa infection].
To explore the influence of infection on the erythrocyte chemokine receptor (ECKR) binding activity in severely scalded rats. The Sprague-Dawley (SD) rats were randomly divided into three group: sham scald group (A), burn and infection group (B) and infection group (C). The B group rats were scalded with 30% total body surface area (TBSA) of III degree, and the rats ECKR binding activity with interleukin-8 (IL-8) as ligand were detected by enzyme-linked immunosorbent assay (ELISA) at 1, 2, 4, 6 and 8 hours after infection. Compared to that in A group, ECKR binding activities declined significantly (both P<0.01) after infection in both of B and C groups, but they increased at 8 hours (P<0.01). ECKR binding activity in B group was significantly less at 2, 8 hours than that in C group after infection (both P<0.05). The declining range of ECKR binding activity was more in B group, in which the decline of ECKR binding activity appeared earlier (2 hours) than that in C (6 hours) group. The infection lead to the decline of ECKR binding activity in burned rats, and the erythrocytes might participate in the chemokine regulation and play a novel role in the infection.


Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7.
Juvenile megaloblastic anaemia 1 (OMIM # 261100) is a rare autosomic disorder characterized by selective cobalamin mal-absorption and inconstant proteinuria produced by mutations in either CUBN or AMN genes. Amnionless, the gene product of AMN, is a transmembrane protein that binds tightly to the N-terminal end of cubilin, the gene product of CUBN. Cubilin binds to intrinsic factor-cobalamin complex and is expressed in the distal intestine and the proximal renal tubule. We report a compound AMN heterozygosity with c.742C>T, p.Gln248X and c.208-2A>G mutations in 2 siblings that led to premature termination codon in exon 7 and exon 6, respectively. It produced a dramatic decrease in receptor activity in urine, despite absence of CUBN mutation and normal affinity of the receptor for intrinsic factor binding. Heterozygous carriers for c.742T and c.208-2G had no pathological signs. These results indicate that amnionless is essential for the correct luminal expression of cubilin in humans.


Geostatistics and Bayesian updating for transmissivity estimation in a multiaquifer system in Manitoba, Canada.
In ground water flow and transport modeling, the heterogeneous nature of porous media has a considerable effect on the resulting flow and solute transport. Some method of generating the heterogeneous field from a limited dataset of uncertain measurements is required. Bayesian updating is one method that interpolates from an uncertain dataset using the statistics of the underlying probability distribution function. In this paper, Bayesian updating was used to determine the heterogeneous natural log transmissivity field for a carbonate and a sandstone aquifer in southern Manitoba. It was determined that the transmissivity in m2/sec followed a natural log normal distribution for both aquifers with a mean of -7.2 and - 8.0 for the carbonate and sandstone aquifers, respectively. The variograms were calculated using an estimator developed by Li and Lake (1994). Fractal nature was not evident in the variogram from either aquifer. The Bayesian updating heterogeneous field provided good results even in cases where little data was available. A large transmissivity zone in the sandstone aquifer was created by the Bayesian procedure, which is not a reflection of any deterministic consideration, but is a natural outcome of updating a prior probability distribution function with observations. The statistical model returns a result that is very reasonable; that is homogeneous in regions where little or no information is available to alter an initial state. No long range correlation trends or fractal behavior of the log-transmissivity field was observed in either aquifer over a distance of about 300 km.


A randomized controlled study of intervention to improve continuity care engagement among HIV-infected persons after release from jails.
Short-term stay, multiple jail admissions and social and financial difficulties are significant obstacles for continuity care engagement (CCE) after release among HIV-infected jail detainees. However, data existing on interventions or strategies to increase post-release CCE among this population are limited. We conducted a randomized controlled study among HIV-infected detainees at Cook County Jail during 2011-2014. The intervention group received telephone contact within 2-4 days of release by a continuity clinic coordinator, who scheduled and informed the ex-detainees of their appointment date within 6 weeks post-release plus standard of care, while the control group received standard of care. The standard of care included comprehensive discharge planning, offering substance abuse treatment and provision of information on how to self-schedule an appointment with the chosen clinics. Of the 166 detainees enrolled, 56 were excluded due to being sent to prison or re-incarcerated within 6 weeks. The final cohort included 55 detainees in each of the groups. The rate of CCE within 6 weeks after release was significantly higher in the intervention group compared to the control group (58% vs. 33%; P = .007). In multivariable logistic regression analysis, being in the control group was the only factor associated with no CCE within 6 weeks (adjusted odds ratio 2.66; 95% confidence interval 1.18-6.00; P = .02). The study findings suggest that the simple telephone contact intervention significantly improved CCE among HIV-infected jail detainees.


[Levels of tPSA and fPSA and count of peripheral blood neutrophils in the diagnosis of prostate cancer].
To investigate the value of combined detection of tPSA, fPSA and peripheral blood neutrophil count (Neut#) in the diagnosis of PCa. This study included 238 cases of PCa, 328 cases of BPH and 303 normal men as healthy controls present at our hospital for medical or physical examination from August 2018 to December 2021. We detected the levels of serum tPSA and fPSA and Neut# of the subjects, and assessed the value of the combined detection in the diagnosis of PCa using logistic regression analysis, ROC curves, Pearman correlation analysis and nonparametric test. There were significant differences in the tPSA and fPSA levels and Neut# between any two of the PCa, BPH and healthy control groups (P < 0.05). The index N of the combined detection of tPSA, fPSA and Neut# showed an evidently higher diagnostic value than that of any single-item detection. The Gleason scores of the subjects were correlated positively with the tPSA and fPSA levels and index N, with the correlation coefficients of 0.184, 0.245 and 0.166 respectively, P < 0.05), and negatively with the Neut#, with the correlation coefficient of -0.168, P < 0.05). Statistically significant differences were observed in the tPSA and fPSA levels, Neut# and index N in those with different Gleason scores (P < 0.05). The combined detection of tPSA, fPSA and Neut# improves the diagnosis of PCa and can be applied clinically as an auxiliary diagnostic method.


Overlapping of nonlinear resonances and the problem of quantum chaos.
The motion of a nonlinearly oscillating particle under the influence of a periodic sequence of short impulses is investigated. We analyze the Schrödinger equation for the universal Hamiltonian. It is shown that the quantum criterion of overlapping of resonances is of the form lambdaK>or=1, where K is the classical coefficient of stochasticity and lambda is the functional defined with the use of Mathieu functions. The area of the maximal values of lambda is determined. The idea about the emerging of quantum chaos due to the adiabatic motion along the curves of Mathieu characteristics at multiple passages through the points of branching is advanced.


[Study of hepatic energy metabolism on rats by six cold property traditional Chinese medicines].
To investigate the common rule hepatic energy metabolism on rats by six cold property of traditional Chinese medicines (TCM). The activities of Na+ - K+ - ATPase, Ca2+ - ATPase and SDH, the content of hepatic glycogen, and the mRNA expression of hepatic uncoupling protein 2 (UCP2) were measured after the rats and been administrated with water extracts of Radix Sophorae Flavescentis, Fructus Gardeniae, Cortex Phellodendri, Radix Scutellariae, Rhizoma Coptidis, Radix Gentianae respectively at 6.0, 7.0, 8.4, 6.0, 7.0, 4.0 g x kg(-1) doses for 30 days, twice a day. The activities of Na+ - K+ - ATPase, Ca2+ - ATPase and SDH were depressed significantly by six cold property TCM. The decreased tendency of SDH was observed by six cold property of TCM, while statistical significance was obtained in Cortex Phellodendri, Radix Scutellariae, Rhizoma Coptidis, Radix Gentianae. The increased tendency of hepatic glycogen content was found by six cold property TCM, while statistical significance was not obtained in six groups. The decreased tendency of the mRNA expression of UCP2 was found by six cold property TCM, while statistical significance was obtained in Radix Sophorae Flavescentis, Cortex Phellodendri, and Radix Scutellariae groups. The six cold property TCM have the good effects on hepatic energy metabolism by decreasing the activity of mitochondria SDH to reduce the production of ATP by decreasing the activities of Na+ - K+ - ATPase, Ca2+ - ATPase to cut down the consumption of ATP, by decreasing the mRNA expression of hepatic UCP2 to decrease the heat production.


Measuring calcium content in plants using NEXAFS spectroscopy.
Calcium is important for the growth and development of plants. It serves crucial functions in cell wall and cell membrane structure and serves as a secondary messenger in signaling pathways relevant to nutrient and immunity responses. Thus, measuring calcium levels in plants is important for studies of plant biology and for technology development in food, agriculture, energy, and forest industries. Often, calcium in plants has been measured through techniques such as atomic absorption spectrophotometry (AAS), inductively coupled plasma-mass spectrometry (ICP-MS), and electrophysiology. These techniques, however, require large sample sizes, chemical extraction of samples or have limited spatial resolution. Here, we used near-edge X-ray absorption fine structure (NEXAFS) spectroscopy at the calcium L- and K-edges to measure the calcium to carbon mass ratio with spatial resolution in plant samples without requiring chemical extraction or large sample sizes. We demonstrate that the integrated absorbance at the calcium L-edge and the edge jump in the fluorescence yield at the calcium K-edge can be used to quantify the calcium content as the calcium mass fraction, and validate this approach with onion epidermal peels and ICP-MS. We also used NEXAFS to estimate the calcium mass ratio in hypocotyls of a model plant, Arabidopsis thaliana, which has a cell wall composition that is similar to that of onion epidermal peels. These results show that NEXAFS spectroscopy performed at the calcium edge provides an approach to quantify calcium levels within plants, which is crucial for understanding plant physiology and advancing plant-based materials.


Conditional, tissue-specific expression of Q205L G alpha i2 in vivo mimics insulin action.
Deficiency of the G protein subunit G alpha i2 that is known to mediate the inhibitory control of adenylylcyclase impairs insulin action [11]. Using the promoter for the phosphoenolpyruvate carboxykinase gene, conditional tissue-specific expression of the constitutively active mutant form (Q205L) of G alpha i2 was achieved in mice harboring the transgene. Expression of Q205L G alpha i2 was detected in liver and adipose tissue of transgenic mice. Whereas the G alpha i2 deficient mice displayed blunted glucose tolerance, the Q205L G alpha i2 expressing mice displayed enhanced glucose tolerance. Hexose transport and the recruitment of GLUT4, but not GLUT1, transporters to the membrane were elevated in adipocytes from Q205L G alpha i2 expressing mice in the absence of insulin. Additionally, hepatic glycogen synthase was found to be activated in Q205L G alpha i2 expressing mice, in the absence of the administration of insulin. Serum insulin levels in transgenic mice fasted overnight were equivalent to those of their control littermates. These data demonstrate that much as G alpha i2 deficiency leads to insulin resistance, expression of Q205L constitutively active G alpha i2 mimics insulin action in vivo, reflecting a permissive role of G alpha i2 in signaling via this growth factor receptor tyrosine kinase linked pathway.


Biological Control of Meloidogyne hapla Using an Antagonistic Bacterium.
We examined the efficacy of a bacterium for biocontrol of the root-knot nematode (RKN) Meloidogyne hapla in carrot (Daucus carota subsp. sativus) and tomato (Solanum lycopersicum). Among 542 bacterial isolates from various soils and plants, the highest nematode mortality was observed for treatments with isolate C1-7, which was identified as Bacillus cereus based on cultural and morphological characteristics, the Biolog program, and 16S rRNA sequencing analyses. The population density and the nematicidal activity of B. cereus C1-7 remained high until the end of culture in brain heart infusion broth, suggesting that it may have sustainable biocontrol potential. In pot experiments, the biocontrol efficacy of B. cereus C1-7 was high, showing complete inhibition of root gall or egg mass formation by RKN in carrot and tomato plants, and subsequently reducing RKN damage and suppressing nematode population growth, respectively. Light microscopy of RKN-infected carrot root tissues treated with C1-7 showed reduced formation of gall cells and fully developed giant cells, while extensive gall cells and fully mature giant cells with prominent cell wall ingrowths formed in the untreated control plants infected with RKNs. These histopathological characteristics may be the result of residual or systemic biocontrol activity of the bacterium, which may coincide with the biocontrol efficacies of nematodes in pots. These results suggest that B. cereus C1-7 can be used as a biocontrol agent for M. hapla.


Oral health-related quality of life in patients on chronic haemodialysis and after kidney transplantation.
The objective of the study was to evaluate oral health-related quality of life (OHRQoL) depending on dental and periodontal situation in patients on haemodialysis (HD) and after kidney transplantation (KTx) compared to healthy controls (HC). OHRQoL was assessed using the German short form of Oral Health Impact Profile (OHIP G14). Dental health was estimated using the decayed, missing and filled teeth index (DMF-T). Periodontal health was classified as healthy/mild or moderate/severe periodontitis. Mann-Whitney U-test, Kruskal-Wallis test, chi-square test and Fisher's test. Eighty-seven HD patients, 39 KTx patients and 91 HC were included. Significant differences in DMF-T, D-T, M-T and F-T scores were identified between groups (P < 0.001). The prevalence of moderate/severe periodontitis was significantly higher in the HD and KTx group compared to HC (P = 0.002). Differences in OHIP G14 between groups were neither clinical relevant nor statistically significant (P = 0.199). A significant effect of DMF-T (P = 0.012), M-T (P < 0.001) and periodontitis (P = 0.023) on the OHIP G14 scores was identified only in HC. Improvement in dental care of HD and KTx patients is required. OHIP G14 values provide a subjectively considered low importance of oral health in HD and KTx patients, leading to need of motivation and sensitisation of these patients.


Reconstruction of urethra using appendix in a patient with cloacal malformation.
We report a case of 21-year-old young woman with congenital cloacal malformation. She was operated at the age of 1.5 years separating the rectum from common opening as a two-stage repair. She was incontinent in the earlier part of her life but she became continent to some extent later in early adulthood. She presented with urinary stress incontinence following delivery of dead fetus of 6 months. She underwent multiple investigations revealing common opening of bladder neck and vagina. A multidisciplinary evaluation was done and she underwent closure of common channel and neourethra reconstruction using pedicled appendix. Patient was continent and voiding by herself on discharge.


Hepmarc: A 96 week randomised controlled feasibility trial of add-on maraviroc in people with HIV and non-alcoholic fatty liver disease.
Maraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration. We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores. Fifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6-7.8) kPa, 325 (IQR 279-351) dB/m and 9.1 (IQR 8.6-9.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target >90%]; 83% (95%CI 70%-92%) participant retention [target >65%]; 5.5% of data were missing [target <20%]. There were noo Serious Adverse Reactions; mild-moderate intensity Adverse Reactions were reported by five participants (5/23, 22% (95%CI 5%-49%)) [target <10%]. All Adverse Reactions resolved. Secondary outcomes: no important differences were seen by treatment group for the change from baseline in LSM, CAP or ELF scores. This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis. Clinical trial registry: ISCRTN, registration number 31461655.


Surgical site infection after colorectal surgery according to the main anesthetic agent: a retrospective comparison between volatile anesthetics and propofol.
Anesthetic agents used for general anesthesia are emerging possible influential factors for surgical site infection (SSI). In this retrospective study, we evaluated the incidence of SSI after colorectal surgery according to the main anesthetic agents: volatile anesthetics vs. propofol. A total 1,934 adult patients, who underwent elective colorectal surgery under general anesthesia between January 2011 and December 2013, were surveyed to evaluate the incidence of SSI: 1,519 using volatile anesthetics and 415 using propofol for main anesthetic agents. Patient, surgery, and anesthesia-related factors were investigated from all patients. Propensity-score matching was performed to reduce the risk of confounding and produced 390 patients in each group. Within the propensity-score matched groups, the incidence of SSI was higher in the volatile group compared with the propofol group (10 [2.6%] vs. 2 [0.5%], OR = 5.0 [95% CI = 1.1-2.8]). C-reactive protein was higher in the volatile group than in the propofol group (8.4 ± 5.6 vs. 7.1 ± 5.3 mg/dl, P = 0.001), and postoperative white blood cells count was higher in the volatile group than in the propofol group (9.2 ± 3.2 × 10(3)/µl vs. 8.6 ± 3.4 × 10(3)/µl, P = 0.041). The results of this study suggest that intravenous anesthesia may have beneficial effects for reducing SSI in colorectal surgery compared to volatile anesthesia.


High transdermal fentanyl requirements in a patient with chronic cancer pain.
To report a case of high transdermal fentanyl dosage requirements in a patient with chronic cancer pain. Clinical studies, review articles, and relevant laboratory information. A 42-year-old woman with cervical cancer was admitted for control of her pain. Her outpatient analgesic regimen was a continuous intravenous infusion of morphine sulfate (MS) via an ambulatory infusion device. Upon admission, supplemental doses of intravenous MS were administered in an effort to eliminate the pain. Transdermal fentanyl therapy was initiated on hospital day 1 at 100 micrograms/h and the MS continuous intravenous infusion dosage was increased. Over the next four days, the patient experienced episodes of inadequate pain control and the transdermal fentanyl dosage was increased in increments of 100 micrograms/h. On hospital day 4 the MS continuous infusion was converted to patient-controlled analgesia (PCA). The patient reported acceptable pain control with a regimen of transdermal fentanyl 500 micrograms/h and MS via PCA and she was discharged home on hospital day 7. This patient's high transdermal fentanyl dosage requirement was related to disease progression. She experienced an acute pain episode that may have been effectively managed by increasing the dosage of her continuous intravenous MS infusion.


The tertiary service for psychosis: Holistic recommendations for people with complex psychosis.
To describe (i) the clinical characteristics of individuals referred to the Tertiary Referral Service for Psychosis (TRSP) and (ii) the recommendations TRSP made for future treatment across psychopharmacological and other intervention domains. Retrospective audit of clinical data collected during the assessment process of individuals who accessed TRSP between 02/06/2020 and 31/12/2022. Categories of recommendations made following collaborative care planning comprised psychopharmacological, neuropsychological, psychological, psychosocial, physical health, substance misuse and other domains. Eighty-two individuals were included, with diagnoses most commonly of schizophrenia (54.9%) and schizoaffective disorder (30.5%). The median PANSS score was 88.0 (73-100). Social occupational functioning was very poor (SOFAS M = 37.0, SD = 15.1). Cognitive functioning was poor (RBANS: M = 74.6; SD: 15.0). 67.1% had physical health comorbidities, with high prevalence of smoking (52.4%) and substance misuse (25.6%). Psychopharmacological recommendations (made for 81.7%) included clozapine trial (25.6%), clozapine dose change/augmentation (22.0%) and rationalisation of polypharmacy (12.2%). Neuropsychological (73.2%), psychological (39.0%) and psychosocial (85.4%) recommendations included access to cognitive remediation, psychological therapy and disability support. Physical health and substance misuse interventions were recommended for 91.5% and 20.7%, respectively. Individuals referred to the TRSP had marked clinical and functional impairments. Holistic collaborative care planning complemented psychopharmacological interventions with psychological, psychosocial and physical healthcare recommendations.


Feasibility Study of Cord Tissue Derived Mesenchymal Stromal Cells in COVID-19-Related Acute Respiratory Distress Syndrome.
Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking. In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety. Ten patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the >70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs. We were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.


Antigen and antibody attachment in ELISA for Aspergillus fumigatus IgG antibodies.
Four commercial antigen extracts of Aspergillus fumigatus were evaluated for use in a rapid enzyme-linked immunosorbent assay (ELISA) for anti-A. fumigatus IgG. Initial binding of both somatic and culture filtrate preparations to a polyvinyl chloride solid phase was concentration dependent and increased with incubation time. Antigen binding to the solid phase was reproducible. Binding of A. fumigatus precipitin-positive serum to bound antigen was rapid. All four A. fumigatus antigens demonstrated similar dose-response curves when tested against pooled sera containing a high titre of A. fumigatus antibodies. Detectable activity in precipitin test-negative sera decreased rapidly with dilution. All the antigen preparations were found to be suitable for ELISA procedures and permit the rapid determination of IgG antibodies to A. fumigatus.


Acute traumatic tetraplegia during pregnancy.
A case of acute traumatic tetraplegia during pregnancy resulting in maternal death is presented, and problems of management are discussed. Difficulties experienced by the mother were intractable urinary tract infection and respiratory insufficiency; those in the neonate were prematurity and the effects of drugs administered to the mother.


Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins.
Phalloidin, the major phallotoxin of the mushroom Amanita phalloides, enters hepatocytes by a carrier-mediated mechanism. The molecular identity of the transport proteins mediating phalloidin uptake was so far unknown. Earlier studies in rat liver indicated that phalloidin may share a common mechanism of uptake with organic anions like bile salts. In the current study on human transporters, we analyzed the uptake of phalloidin into transfected HEK293 cells stably expressing the recombinant hepatocyte-specific organic anion uptake transporters OATP2 (also termed OATP1B1, OATP-C, LST1, symbol SLC21A6) or OATP8 (OATP1B3 or SLC21A8). Time-dependent uptake of phalloidin was observed with SLC21A6-expressing cells and was inhibited by typical substrates of SLC21A6 such as bromosulfophthalein or cholyltaurine. A K(m) value of 39+/-11 micro M was determined for SLC21A6-mediated phalloidin uptake. Additional inhibitors of phalloidin uptake mediated by SLC21A6 included the immunosuppressive drugs cyclosporin A, FK506, and rapamycin, whereas alpha-amanitin was only a weak inhibitor. Cyclosporin A was a most potent competitive inhibitor for SLC21A6-mediated phalloidin transport with a K(i) value of 51 nM.


[Avulsion of the skin of the penis and scrotum].
The authors present a case report of traumatic avulsion of the skin of the penis and scrotum. Surgical treatment was performed in one surgical stage a few hours after the accident. The skin repair of the penis was carried out with a skin graft, while scrotum reconstruction was performed with fasciocutaneous flaps of the inner face of the thighs, with supero-medial pedicle, achieving a good result. The authors justify their choice of procedure, also mentioning the other methods most employed.


Full open-framework batteries for stationary energy storage.
New types of energy storage are needed in conjunction with the deployment of renewable energy sources and their integration with the electrical grid. We have recently introduced a family of cathodes involving the reversible insertion of cations into materials with the Prussian Blue open-framework crystal structure. Here we report a newly developed manganese hexacyanomanganate open-framework anode that has the same crystal structure. By combining it with the previously reported copper hexacyanoferrate cathode we demonstrate a safe, fast, inexpensive, long-cycle life aqueous electrolyte battery, which involves the insertion of sodium ions. This high rate, high efficiency cell shows a 96.7% round trip energy efficiency when cycled at a 5C rate and an 84.2% energy efficiency at a 50C rate. There is no measurable capacity loss after 1,000 deep-discharge cycles. Bulk quantities of the electrode materials can be produced by a room temperature chemical synthesis from earth-abundant precursors.


A systematic approach to using case studies in health informatics education.
The complexity of health informatics (HI) projects necessitates a solid base of skills and knowledge in a variety of different fields. Case studies are an excellent way to introduce this complexity without overwhelming students. This paper makes a contribution to HI education by presenting a systematic approach to introducing HI concepts to future health informatics professionals (HIPs) and to health care professionals and administrators who need a solid grounding to participate in HI projects.


Leisure time physical activity and mortality.
Some studies indicate that a large part of the beneficial effect of physical activity on mortality is confined to a threshold effect of participation. Self-reported physical activity was investigated in relation to all-cause mortality in the Danish Diet, Cancer and Health cohort, including 29,129 women and 26,576 men aged 50-64 years at baseline 1993-1997. Using Cox proportional hazards models we investigated the associations between mortality rate and leisure time physical activity by exploring 1) participation (yes/no) in each type of activity; 2) a simple dose-response relationship with hours spent on each activity, supplemented with indicators of participation in each activity; and 3) inflexion or nonmonotonic dose-response relationships using linear splines. A total of 2696 women and 4044 men died through March 2010. We found lower mortality with participation in sports (for women, mortality rate ratio = 0.75, 95% confidence interval = 0.69-0.81; for men, 0.78, 0.73-0.84), cycling (for women, 0.77, 0.71-0.84; for men, 0.90, 0.84-0.96), or gardening (for women, 0.84, 0.78-0.91; for men, 0.73, 0.68-0.79) and in men participating in do-it-yourself activity (0.77, 0.71-0.84). A weak adverse dose response was seen for walking and gardening, but the association was small (1-2% increase in mortality per additional hour). We found no signs of inflexion or nonmonotonic effects of additional hours spent on each activity. Mortality was lower with participation in specific leisure time physical activities, but not with more time spent on those activities. This could suggest that avoiding a sedative lifestyle is more important than a high volume of activity. Nonparticipation in these types of physical activity may be considered as risk factors.


Comparison of conventional and sustained delivery of antioxidants to suppress the caov-3 cell lin in ovarian cancer.
The objective of this study was to investigate the synergistic effect of Thymoquinone (TQ) and Epigallocatechin-3-gallate (EGCG) using Caov-3 cell line as a model. A total of 144 wells were plated with 10^5 Caov-3 ovarian cancer cells. The wells were divided into groups of 72 wells for conventional and sustained delivery, respectively. Each group was subdivided into 4 groups of 6 wells. Group 1 served as control and groups 2, 3, and 4 were treated with TQ (16 µM), EGCG (3 µg/ml), and TQ plus EGCG, respectively. Biomarkers evaluations were performed following standard lab techniques. The results of the study revealed: conventional delivery of TQ, EGCG, and the combination did not induce intracellular oxidative stress (glutathione levels) at 24, 48, and 72 hours; however, sustained delivery of all agents showed significant difference from the control at 72 hours; and there was no significant difference at 24 and 48 hours. Overall conclusion: the route of potent agents to manipulate ovarian cancer cells is highly dependent on the route of administration.


Contribution of the superior atrioventricular cushion to the left ventricular infundibulum. Experimental study on the chick embryo.
The role of the superior atrioventricular cushion in the normal development of the left ventricular infundibulum was experimentally studied in the chick embryo. 178 embryos at stages 19-24 of Hamburger and Hamilton were selectively labeled using gelatin-india ink; afterward embryos were reincubated until the mature heart stage, in which the final location of the labels was determined. In addition, anatomical microscopic studies were carried out on the chick embryo heart at different stages of the development. 91 embryos were obtained at the mature heart stage, 46 of which were normal. In 82,6% of these 46 embryos labels were found in the left ventricular infundibulum and were distributed in the following regions: (1) base of the free portion of the anteroseptal mitral leaflet (mitroaortic continuity); (2) the same region plus the left surface of the anterior basal portion of the ventricular septum, and (3) the left surface of the anterior basal portion of the ventricular septum. Anatomical microscopic studies showed that the superior atrioventricular cushion appears at stage 18, fusing with the inferior cushion at stage 28. Our results permit us to conclude that the superior atrioventricular cushion plays an important role in the normal development of the left ventricular infundibulum, and it contributes in the posterolateral and anteromedial wall formation.


[Bochdalek's diaphragmatic hernia with delayed symptomatology].
We report a case of congenital diaphragmatic hernia detected in an 8-month-old boy with previously normal pulmonary X ray. This case shows that some Bochdalek hernias may appear at a later date and are sometimes intermittent.


The effect of diuretics on red blood cell microrheological parameters in female hypertensive patients.
This study was designed to examine changes of hemorheological parameters and red cell aggregation particularly in essential arterial hypertension subjects receiving antihypertensive diuretic therapy. Fifty six female subjects were enrolled in this study. Thirty seven subjects (group I) were treated for four weeks with Hydrochlorothiaszide (25 mg/day); Nineteen patients (group II) were infused with dose of furosemide 40 mg i.v. Both prior to and following drug treatment for four weeks and four hours after furosemide infusion hemorheological measurements included plasma viscosity; hematocrit, total plasma protein, red cell rigidity index (Tk) and RBC aggregation indices. In addition to this protocol the erythrocytes of patients of group II were incubated with furosemide (0.03 mM; for 30 min at 37 degrees C) to study a direct furosemide effect on red cell aggregation. Treatment and infusion with each of the two drugs significantly (p<0.05) reduced blood pressure in both groups. However, the hemorheological effects of hydrochlorothiaszide therapy were not significant. The effect of furosemide infusion and red cell incubation with it led to significant RBCA elevation. These results thus suggest that the rheologic effects of saluretic diuretics therapy were not significant. Single furosemide infusion and using it in vitro resulted in strong effect of red cell aggregation increase.


Spontaneous improvement of bilateral clinodactyly of the little finger with trapezoidal phalanx: a case report with a 15-year follow-up.
Clinodactyly can be produced by a longitudinal epiphyseal bracket that generates either a 'delta' or 'trapezoidal' phalanx. We present a case with a 15-year follow-up of bilateral clinodactyly of the little finger, to emphasize a 'wait-and-see' approach as self-remodelling of his phalanges occurred during growth.


Potential mechanisms of CD133 in cancer stem cells.
Cancer stem cells (CSCs) have emerged as an underlying cause of cancer relapse and resistance to treatment. Initially, biomarkers were used to identify and isolate distinct cell populations. Several CSC markers have been identified from many types of tumors, and these markers are also being used for isolation and enrichment of CSCs. Cluster of differentiation CD133 is a well-characterized CSC marker, and it is involved in tumor cell proliferation, metastasis, tumorigenesis, and recurrence, as well as chemo- and radio-resistance. However, the mechanisms involved in CD133-mediated induction of CSC properties have not yet been elucidated. Here, we introduce and summarize the functions of CD133 in CSCs and suggest new mechanisms that may be of note in our approach to developing novel cancer therapies.


Footprint of a Bioresorbable Vascular Scaffold in Computed Tomography Coronary Angiogram at 5-Year Follow-up.
The Absorb bioresorbable vascular scaffold (Abbott Vascular) does not have an artifact on computed tomography coronary angiography (CTCA); the extent/location of the stent in situ can only be assessed by localizing its radiopaque platinum markers in a non-contrast CTCA. The characteristic appearance of BVS on CTCA should be interpreted as the footprint of a resorbed BVS, instead of a calcified plaque.


[Creation of a regional stroke network in Tours hospital (France): consequences for stroke care and thrombolysis].
Our university hospital serves a population of 300 000 inhabitants. Stroke is the leading cause of admission in our department of neurology. In June 2003, when the Emergency Department (ED) was closed in our institution, was created an acute stroke network (ASN), comprising 2 beds of direct admission and thrombolysis in the intensive care unit, and 4 beds dedicated to stroke care in the department of neurology, in which standardized stroke care protocols were implemented. The aim of this study was to evaluate changes in stroke care related to the creation of the ASN in terms of delays of arrival, imaging, use of intravenous (IV) thrombolysis, and outcome of patients. We conducted a prospective study during 18 months to evaluate characteristics of patients admitted with suspected stroke or transient ischemic attack (TIA) in the newly created ASN and to assess conditions of treatment with IV thrombolysis in terms of safety and efficacy. We also compared the outcome data before and after the creation of the ASN. For each patient admitted in our hospital for suspected stroke or TIA, were prospectively collected clinical and outcome data (age, mode of transport, delay of arrival after the onset of symptoms (OS), treatment with IV thrombolysis, outcome and discharge). This study was conducted in the ED during six months in 2002, and in the ASN during 18 months, for all patients admitted for stroke. Three hundred and sixty four patients were admitted in the ASN. Emergency medical services (EMS) were used in half of cases for transport, and median delay of admission after the OS was 2h and 52 min. Median delay of imaging was 1 h and 45 min. Seventeen patients (8.5 p. 100 of ischemic stroke patients) were treated with IV thrombolysis, with an initial good outcome in 9 patients, 7 with a dramatic recovery). The main reason for therapeutic abstention for untreated patients admitted in the first 3 hours was a mild deficit with a NIHSS<6. Compared with the previous management in the ED, patients in the ASN were younger, had more severe neurological symptoms, the EMS transport was the main mode of transport (versus used in 17 p. 100 of cases in 2002), and the delay of admission was significantly lower: 2 h 52 versus 5 h 10 (p<0.02). After adjustment on the main predictive factors, only patients with hemorrhagic strokes had a better outcome after the creation of the ASN. Creation of an ASN was associated with a significant decrease of admission and imaging delays, due to a strong collaboration with EMS, and with a better outcome for hemorrhagic stroke patients. Treatment with intravenous thrombolysis in the first 3 hours could be used widely and was efficient and safe. However, the creation of dedicated stroke units for all stroke patients remains necessary to improve quality of care and outcome.


[Production of anti-recombinant human arrest defective 1 protein (hARD1) monoclonal antibodies for assaying human breast cancer tissues].
Human arrest defective 1(hARD1) is an acetyltransferase catalyzing the N-terminal acetylation of proteins after translation. The high expression of hARD1 could be an indicator of the breast cancer. In current study, we produced an anti-hARD lp monoclonal antibody that could specifically recognize ARD1 in breast cancer tissues by using the immunohistochemical assay. The full-length His-tag hARD1 protein (1-235 aa) was over-expressed in Escherichia coli, and purified recombinant protein was injected into Balb/c mice to perform immunization procedure. Eight stable positive monoclonal cell lines were isolated. ELISA results demonstrated that all light chains of antibodies were kappa, and the heavy chains displayed three subtypes IgG1, IgG2a and IgG2b, respectively. A monoclonal antibody, which could specifically recognize hARD1 protein in breast cancer tissues, was identified by screening different cancer tissues using antibody-specificity method. Further, the specificity of the antibody was confirmed by Western blotting analysis. Our study would facilitate breast cancer diagnosis by using this ARD1 monoclonal antibody in clinic. Also, this antibody could be used as an important tool for further investigating the role of ARD1 in tumorigenesis.


Population genetic signatures of diffuse co-evolution between leaf-cutting ants and their cultivar fungi.
Switching of symbiotic partners pervades most mutualisms, despite mechanisms that appear to enforce partner fidelity. To investigate the interplay of forces binding and dissolving mutualistic pairings, we investigated partner fidelity at the population level in the attine ant-fungal cultivar mutualism. The ants and their cultivars exhibit both broad-scale co-evolution, as well as cultivar switching, with short-term symbiont fidelity maintained by vertical transmission of maternal garden inoculates via dispersing queens and by the elimination of alien cultivar strains. Using microsatellite markers, we genotyped cultivar fungi associated with five co-occurring Panamanian attine ant species, representing the two most derived genera, leaf-cutters Atta and Acromyrmex. Despite the presence of mechanisms apparently ensuring the cotransmission of symbiont genotypes, different species and genera of ants sometimes shared identical fungus garden genotypes, indicating widespread cultivar exchange. The cultivar population was largely unstructured with respect to host ant species, with only 10% of the structure in genetic variance being attributable to partitioning among ant species and genera. Furthermore, despite significant genetic and ecological dissimilarity between Atta and Acromyrmex, generic difference accounted for little, if any, variance in cultivar population structure, suggesting that cultivar exchange dwarfs selective forces that may act to create co-adaptive ant-cultivar combinations. Thus, binding forces that appear to enforce host fidelity are relatively weak and pairwise associations between cultivar lineages and ant species have little opportunity for evolutionary persistence. This implicates that mechanisms other than partner fidelity feedback play important roles in stabilizing the leafcutter ant-fungus mutualism over evolutionary time.


Simultaneous pectus excavatum correction and lung transplantation-A case series.
Severe chest wall deformities are considered an absolute contraindication for lung transplantation. The significantly impaired chest compliance associated with pectus excavatum is thought to result in a high risk of postoperative respiratory complications and significant morbidity and mortality. We herein report our pooled institutional experience consisting of 3 patients who underwent bilateral lung transplantation and simultaneous correction of a pectus excavatum. Two of the patients were children and 1 patient had severe asymmetric pectus. All patients received a size-reduced double lung transplant and the deformity was corrected by a Nuss or modified Ravitch procedure. The perioperative course was complicated by prolonged weaning requiring tracheostomy in 2 of the 3 patients. However, long-term results were good and all 3 patients are alive in excellent clinical condition 72, 60, and 12 months after the transplantation. This case series demonstrates that patients with severe chest wall deformities should not a priori be excluded from lung transplantation, and a combined approach is feasible for selected patients.


The limb bud Shh-Fgf feedback loop is terminated by expansion of former ZPA cells.
Vertebrate limb outgrowth is driven by a positive feedback loop involving Sonic Hedgehog (Shh), Gremlin, and Fgf4. By overexpressing individual components of the loop at a time after these genes are normally down-regulated in chicken embryos, we found that Shh no longer maintains Gremlin in the posterior limb. Shh-expressing cells and their descendants cannot express Gremlin. The proliferation of these descendants forms a barrier separating the Shh signal from Gremlin-expressing cells, which breaks down the Shh-Fgf4 loop and thereby affects limb size and provides a mechanism explaining regulative properties of the limb bud.


Characterization of a monoclonal antibody that selectively recognizes a subset of Entamoeba histolytica isolates.
Monoclonal antibody 2D7.10 recognized an antigen present in seven of nine isolates of axenically cultured Entamoeba histolytica and absent in all other Entamoeba isolates studied. The antigen was absent in two isolates: 200:NIH and Rahman. All nine isolates belonged to pathogenic zymodeme II. Western blot (immunoblot) analysis and treatment with periodate and the proteolytic enzyme trypsin suggest that the antigen recognized by 2D7.10 is a carbohydrate moiety.


SIRT1-ZEB1-positive feedback promotes epithelial-mesenchymal transition process and metastasis of osteosarcoma.
Osteosarcoma is the most common malignant bone cancer that mainly affects children and young adults. Recently, the NAD+ -dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in the development of malignant tumors. The study aimed to investigate the role of SIRT1 in osteosarcoma and explore its underlying oncogenic mechanisms. The prognostic value of SIRT1 in osteosarcoma was assessed through detection of SIRT1 expression based on osteosarcoma biopsy tissue. Then, to further investigate the effect of SIRT1 in osteosarcoma, osteosarcoma cells were treated with small interfering RNA SIRT1 and overexpressed SIRT1 to detect the cell migration, invasion, and epithelial-mesenchymal transition (EMT). The levels of SIRT1 expression were significantly higher in osteosarcoma tissues than those in adjacent normal tissues, and the SIRT1 protein level may be coupled with metastatic and poor prognosis risk in patients with osteosarcoma. Moreover, SIRT1 silencing inhibited the migration as well as invasion ability of osteosarcoma cells in vitro, and SIRT1 upregulation reversed those effects. Finally, we found that SIRT1-ZEB1-positive feedback enhanced the EMT process and metastasis of osteosarcoma. Altogether, the results of the current study revealed that high levels of SIRT1 might be a biomarker for a high metastatic rate in patients with osteosarcoma, which suggested that inhibition of SIRT1 might be promising for the therapeutics of osteosarcoma.


The prevalence of current major depression and dysthymia in a Norwegian general practice.
Existing studies suggest that depression is underdiagnosed and undertreated in general practice, and that the known prevalence of this mood disorder in a primary care population may represent only the "tip of the iceberg'. A total of 100 consecutive patients in an average Norwegian general practice were tested, of whom 31 patients were diagnosed as having a depressive illness in this study; 28 patients were diagnosed as having current major depression and three as having dysthymia. In total, 21 of the 28 patients with current major depression presented with other symptoms as their major complaints at the consultation in which they were tested. Twelve of these 21 patients had some kind of pain problem.


Pervasive antibiotic misuse in the Cambodian community: antibiotic-seeking behaviour with unrestricted access.
Antibiotic misuse is widespread in resource-limited countries such as Cambodia where the burden of infectious diseases is high and access to antibiotics is unrestricted. We explored healthcare seeking behaviour related to obtaining antibiotics and drivers of antibiotic misuse in the Cambodian community. In-depth interviews were held with family members of patients being admitted in hospitals and private pharmacies termed pharmacy attendants in the catchment areas of the hospitals. Nurses who run community primary healthcare centres located within the hospital catchment areas were invited to attend focus group discussions. Nvivo version 10 was used to code and manage thematic data analysis. We conducted individual interviews with 35 family members, 7 untrained pharmacy attendants and 3 trained pharmacists and 6 focus group discussions with 30 nurses. Self-medication with a drug-cocktail was widespread and included broad-spectrum antibiotics for mild illness. Unrestricted access to antibiotics was facilitated by various community enablers including pharmacies or drug outlets, nurse suppliers and unofficial village medical providers referred to as "village Pett" whose healthcare training has historically been in the field and not at university. These enablers supplied the community with various types of antibiotics including broad spectrum fluoroquinolones and cephalosporins. When treatment was perceived to be ineffective patients would prescriber-shop various suppliers who would unfailingly provide them with antibiotics. The main driver of the community's demand for antibiotics was a mistaken belief in the benefits of antibiotics for a common cold, high temperature, pain, malaria and 'Roleak' which includes a broad catch-all for perceived inflammatory conditions. For severe illnesses, patients would attend a community healthcare centre, hospital, or when their finances permitted, a private prescriber. Pervasive antibiotic misuse was driven by a habitual supplier-seeking behaviour that was enabled by unrestricted access and misconceptions about antibiotics for mild illnesses. Unofficial suppliers must be stopped by supporting existing regulations with tough new laws aimed at outlawing supplies outside registered pharmacies and fining registered pharmacist/owners of these pharmacies for supplying antibiotics without a prescription. Community primary healthcare centres must be strengthened to become the frontline antibiotic prescribers in the community thereby enabling the community's access to inexpensive and appropriate healthcare. Community-based education program should target appropriate health-seeking pathways and the serious consequences of antibiotic misuse.


Immunological abnormalities in the tonsils of patients with IgA nephropathy: inversion in the ratio of IgA: IgG bearing lymphocytes and increased polymeric IgA synthesis.
In the last few years the mucosal origin of the IgA deposited in the kidneys of patients with IgA nephropathy has been examined by several investigators. We have previously presented evidence that polymeric IgA may have a predominant role in the pathogenesis of IgA nephropathy. Taking into account that these patients often present with macroscopic haematuria following respiratory tract infections we have studied the possible existence of immunological abnormalities in the tonsils of patients with IgA nephropathy. Six patients and 13 controls suffering from chronic tonsillitis were submitted to tonsillectomy. Patients with IgA nephropathy showed a significant increase (P less than 0.00025) in IgA bearing lymphocytes (14.4 +/- 2.3) and a significant decrease (P less than 0.025) in IgG bearing lymphocytes (20.5 +/- 4.6) compared to the control group (2.9 +/- 1.4 and 31.6 +/- 3.6, respectively). After 7 days of culture with pokeweed mitogen the percentage of tonsillar cells producing polymeric IgA was significantly higher in the patients than in the controls (66.5 +/- 12.6 vs 33.4 +/- 10.3; P less than 0.005). These results also suggest a mucosal origin for the IgA deposited in the kidneys of these patients. Our data are consistent with the existence of an immunoregulatory dysfunction in the secretory immune system of patients with IgA nephropathy.


Peri-operative anticoagulant effects of heparinization for carotid endarterectomy.
The question of whether or not to reverse heparin following carotid endarterectomy is a topic of debate. The potential reduction of the risk of thrombosis at the endarterectomy site with non-reversal has to be measured against a potential increase in the risk of wound haematoma. This study prospectively followed activated clotting time (ACT) of 42 consecutive patients undergoing carotid endarterectomy. A standard heparin dose of 100 units/kg was used, and heparin reversal was employed only if the wound appeared excessively haemorrhagic at the procedure's completion. Heparin was reversed in 11 patients. Following heparin administration, ACT increased to a mean 2.72 +/- 0.09 times baseline (range 1.84-4.07), and fell with time, until at 3 h after heparin administration mean ACT in the non-reversed patients was 1.48 +/- 0.03 times baseline (range 1.1-2.03). There was one postoperative neurological event (2%), a contralateral hemisphere stroke. No patient developed a frank wound haematoma requiring evacuation, although three patients (7% of the total study group, 9% of patients not receiving heparin reversal) developed neck swelling and symptoms of airway compromise, and were intubated. Measurements of ACT suggest that a heparin dose of 100 units/kg achieves an adequate anticoagulant level in the operative and early postoperative phase, when thrombosis is most likely to occur, and is not associated with an increased risk of wound haematoma. If heparin is to be selectively reversed in patients felt to be at high risk of postoperative haematoma, the decision should be based on an objective measurement such as ACT, and not the surgeon's impression of wound haemostasis.


Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine.
The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates (n = 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring M. tuberculosis drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of inhA gene promoter mutations, a diversity of mutation types in the rpoB resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.


Poly(ADP-ribose) polymerases regulate cell division and development in Arabidopsis roots.
Root organogenesis involves cell division, differentiation and expansion. The molecular mechanisms regulating root development are not fully understood. In this study, we identified poly(adenosine diphosphate (ADP)-ribose) polymerases (PARPs) as new players in root development. PARP catalyzes poly(ADP-ribosyl)ation of proteins by repeatedly adding ADP-ribose units onto proteins using nicotinamide adenine dinucleotide (NAD+ ) as the donor. We found that inhibition of PARP activities by 3-aminobenzomide (3-AB) increased the growth rates of both primary and lateral roots, leading to a more developed root system. The double mutant of Arabidopsis PARPs, parp1parp2, showed more rapid primary and lateral root growth. Cyclin genes regulating G1-to-S and G2-to-M transition were up-regulated upon treatment by 3-AB. The proportion of 2C cells increased while cells with higher DNA ploidy declined in the roots of treated plants, resulting in an enlarged root meristematic zone. The expression level of PARP2 was very low in the meristematic zone but high in the maturation zone, consistent with a role of PARP in inhibiting mitosis and promoting cell differentiation. Our results suggest that PARPs play an important role in root development by negatively regulating root cell division.