Elucidation of the role of the methylene-tetrahydromethanopterin dehydrogenase MtdA in the tetrahydromethanopterin-dependent oxidation pathway in Methylobacterium extorquens AM1.
The methylotroph Methylobacterium extorquens AM1 oxidizes methanol and methylamine to formaldehyde and subsequently to formate, an intermediate that serves as the branch point between assimilation (formation of biomass) and dissimilation (oxidation to CO₂). The oxidation of formaldehyde to formate is dephosphotetrahydromethanopterin (dH₄MPT) dependent, while the assimilation of carbon into biomass is tetrahydrofolate (H₄F) dependent. This bacterium contains two different enzymes, MtdA and MtdB, both of which are dehydrogenases able to use methylene-dH₄MPT, an intermediate in the oxidation of formaldehyde to formate. Unique to MtdA is a second enzymatic activity with methylene-H₄F. Since methylene-H₄F is the entry point into the biomass pathways, MtdA plays a key role in assimilatory metabolism. However, its role in oxidative metabolism via the dH₄MPT-dependent pathway and its apparent inability to replace MtdB in vivo on methanol growth are not understood. Here, we have shown that an mtdB mutant is able to grow on methylamine, providing a system to study the role of MtdA. We demonstrate that the absence of MtdB results in the accumulation of methenyl-dH₄MPT. Methenyl-dH₄MPT is shown to be a competitive inhibitor of the reduction of methenyl-H₄F to methylene-H₄F catalyzed by MtdA, with an estimated Ki of 10 μM. Thus, methenyl-dH₄MPT accumulation inhibits H₄F-dependent assimilation. Overexpression of mch in the mtdB mutant strain, predicted to reduce methenyl-dH₄MPT accumulation, enhances growth on methylamine. Our model proposes that MtdA regulates carbon flux due to differences in its kinetic properties for methylene-dH₄MPT and for methenyl-H₄F during growth on single-carbon compounds.


Optimization of photodynamic therapy using negative pressure.
The goal of this study is to demonstrate an alternative procedure to perform topical photodynamic therapy (PDT). Here, we propose the combined use of negative pressure and a 5-Aminolevulinic acid (5-ALA) cream occlusion to increase protoporphyrin IX (PPIX) formation. PDT using topical 5-ALA as a prodrug and precursor of PPIX has been used in the treatment and diagnosis of different types of cancer and skin diseases. The use of 5-ALA offers many advantages as a localized and non-systemic application, but it shows limitations in relation to skin penetration. Many authors have discussed the limitations of 5-ALA penetration through the skin. The skin penetration of 5-ALA can be optimized using mechanical devices associated with typical PDT procedure. For this study, 20% 5-ALA cream was applied to a 9 cm(2) area of skin, and an occlusive dressing was placed. The PPIX production was collected at the skin surface, using fluorescence spectroscopy and widefield fluorescence imaging, for 7 h, and after 24 h. We observed that in the presence of negative pressure therapy, the PPIX production, distribution, and elimination are greater and faster than in the control group. The PPIX formation was ∼30% in deeper skin layers, quantified by fluorescence spectroscopy analysis, and ∼20% in surface skin layers, quantified by widefield fluorescence imaging analysis. Negative pressure induction can also help PDT application in the case of inefficient PPIX production. These results can be useful for optimizing the PDT.


Regulation of bacterial gene expression by ribosome stalling and rescuing.
Ribosome is responsible for protein synthesis and is able to monitor the sequence and structure of the nascent peptide. Such ability plays an important role in determining overall gene expression profile of the bacteria through ribosome stalling and rescuing. In this review, we briefly summarize our current understanding of the regulation of gene expression through ribosome stalling and rescuing in bacteria, as well as mechanisms that modulate ribosome activity. Understanding the mechanisms of how bacteria modulate ribosome activity will provide not only fundamental insights into bacterial gene regulation, but also new candidate targets for the development of novel antimicrobial agents.


Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): I. Seasonal patterns and effects of stress and adrenocorticotropic hormone.
The secretion of steroids from the adrenal gland is a classic endocrine response to perturbations that can affect homeostasis. During an acute stress response, glucocorticoids (GC), such as corticosterone (CORT), prepare the metabolic physiology and cognitive abilities of an animal in a manner that promotes survival during changing conditions. Although GC functions during stress are well established, much less is understood concerning how adrenal androgens, namely dehydroepiandrosterone (DHEA) are influenced by stress. I conducted three field studies (one experimental and two descriptive) aimed at identifying how both CORT and DHEA secretion in free-living male northern cardinals (Cardinalis cardinalis), vary during acute stress; across different circulations (brachial vs. jugular); in response to ACTH challenge; and during the annual cycle. As predicted, restraint stress increased plasma CORT, but unexpectedly DHEA levels decreased, but the latter effect was only seen for blood sampled from the jugular vein, and not the brachial. The difference in DHEA between circulations may result from increased neural uptake of DHEA during stress. Injection with exogenous adrenocorticotropic hormone (ACTH) increased CORT concentrations, but failed to alter DHEA levels, thus suggesting ACTH is not a direct regulator of DHEA. Monthly field sampling revealed distinct seasonal patterns to both initial and restraint stress CORT and DHEA levels with distinct differences in the steroid milieu between breeding and non-breeding seasons. These data suggest that the CORT response to stress remains relatively consistent, but DHEA secretion is largely independent of the response by CORT. Although CORT functions have been well-studied in wild animals, little research exists for the role of DHEA and their variable relationship sets the stage for future experimental research addressing steroid stress responses.


Airbag asthma: a case report and review of the literature.
Although airbags are a significant development in automobile safety, they have brought with them new medical problems. To describe a case of new-onset asthma occurring after exposure to a deployed airbag's contents. A 47-year-old man had a 2.5-year history of chest tightness, decreased exercise tolerance, and nocturnal and activity-associated cough beginning after a head-on motor vehicle collision when he was driving an automobile equipped with dual driver-passenger airbags. The collision activated both airbags, with the driver's side airbag breaking open, filling the automobile with particulates. The driver remained in the car for 3 minutes and developed acute shortness of breath and chest tightness for the first time in his life. He had a smoking history of 1 pack-year 20 years earlier. Before that time he could exercise frequently, running for 30 minutes almost daily without difficulty. After the collision, he had respiratory symptoms at rest and after exercise, requiring daily control and rescue medication. Subsequently, he developed bronchospasm following exposure to nonspecific agents, which he had never previously experienced. Skin test reactivity was detectable only to dust mite. Methacholine challenge results were markedly positive at 8 weeks and 2.5 years after the incident. Video laryngoscopy revealed normal vocal cord appearance and function. Our patient represents the first case, to our knowledge, of new-onset, persistent, irritant-induced asthma following airbag deployment. Physicians should be aware of its possibility after airbag exposure, since prompt institution of aggressive therapy may improve patient outcome and dampen or prevent persistent disease.


e-Drug3D: 3D structure collections dedicated to drug repurposing and fragment-based drug design.
In the drug discovery field, new uses for old drugs, selective optimization of side activities and fragment-based drug design (FBDD) have proved to be successful alternatives to high-throughput screening. e-Drug3D is a database of 3D chemical structures of drugs that provides several collections of ready-to-screen SD files of drugs and commercial drug fragments. They are natural inputs in studies dedicated to drug repurposing and FBDD. e-Drug3D collections are freely available at http://chemoinfo.ipmc.cnrs.fr/e-drug3d.html either for download or for direct in silico web-based screenings.


Surgery for 'asymptomatic' mild primary hyperparathyroidism improves some clinical symptoms postoperatively.
Most primary hyperparathyroidism (pHPT) patients do not conform to the guidelines for parathyroidectomy established by an international panel of specialists and have a mild pHPT. This group is typically defined as 'asymptomatic'. The primary aim of this study was to determine symptom improvement in this 'asymptomatic' group after parathyroidectomy. Secondly, we aimed to create a preoperative clinical score predicting postoperative symptom resolution. A prospective nonrandomized study included patients with mild pHPT. A questionnaire (22 items) was given to 'asymptomatic' patients preoperatively and at 3, 6, and 12 postoperative months. A logistic regression was performed to create a preoperative clinical score. One hundred and sixteen patients were included. Postoperatively, HPT was resolved in 98% of patients. Twelve of 22 nonspecific symptoms were improved at 1 year. Subgroups analysis showed a greater improvement in patients <70 years and those with a serum calcium level ≥2.6 mmol/l preoperatively. A clinical score, based on age and five symptoms, was established to predict the clinical improvement after surgery in mild pHPT patients with a positive predictive value of 81%. Patients with asymptomatic pHPT have clinical improvement of their symptoms postoperatively even after 1 year. Younger patients and those with higher preoperative calcium levels show the best improvement.


A prospective study of percutaneous vertebroplasty in patients with myeloma and spinal metastases.
To assess patient outcome in a consecutive series of patients with myeloma and spinal metastases who underwent percutaneous vertebroplasty. Data were gathered prospectively on all patients undergoing percutaneous vertebroplasty between June 2001 and June 2010. Outcome measures included visual analogue pain scores (VAS) and Roland-Morris Questionnaire (RMQ) in patients treated since 2005 as well as complications and long-term outcome in all patients. One hundred and twenty-eight patients underwent percutaneous vertebroplasty for myeloma (n=41) or spinal metastases (n=87) over a 9 year period. VAS scores fell from 7.75 ± 1.88 pre-vertebroplasty to 4.77 ± 2.69 post-vertebroplasty (p=0.001). RDQ scores improved from 18.55 ± 4.79 to 13.5 ± 6.96 (p=0.001). Complications were recorded in three patients: cement extension to vena cava (n=1), local haematoma (n=1), and loss of sensation over T1 dermatome (n=1). The Kaplan-Meier estimate of 5 year survival post-vertebroplasty was 40% for patients with myeloma and 25% for those with metastases. This large prospective study demonstrates percutaneous vertebroplasty reduces pain and improves disability in patients from intractable pain from myeloma or spinal metastases and now forms an important part of the multimodality treatment for these patients.


Examining multi-objective deep reinforcement learning frameworks for molecular design.
Drug design and optimization are challenging tasks that call for strategic and efficient exploration of the extremely vast search space. Multiple fragmentation strategies have been proposed in the literature to mitigate the complexity of the molecular search space. From an optimization standpoint, drug design can be considered as a multi-objective optimization problem. Deep reinforcement learning (DRL) frameworks have demonstrated encouraging results in the field of drug design. However, the scalability of these frameworks is impeded by substantial training intervals and inefficient use of sample data. In this paper, we (1) examine the core principles of deep or multi-objective RL methods and their applications in molecular design, (2) analyze the performance of a recent multi-objective DRL-based and fragment-based drug design framework, named DeepFMPO, in a real-world application by incorporating optimization of protein-ligand docking affinity with varying numbers of other objectives, and (3) compare this method with a single-objective variant. Through trials, our results indicate that the DeepFMPO framework (with docking score) can achieve success, however, it suffers from training instability. Our findings encourage additional exploration and improvement of the framework. Potential sources of the framework's instability and suggestions of further modifications to stabilize the framework are discussed.


Development of Cutaneous Wound in Diabetic Immunocompromised Mice and Use of Dental Pulp-Derived Stem Cell Product for Healing.
Chronic nonhealing wounds impact nearly 15% of Medicare beneficiaries (8.2 million) in the United States costing $28-$32 billion annually. Despite advancement in wound management, approximately 8% of diabetic Medicare beneficiaries have a foot ulcer and 1.8% will have an amputation. The development of a regenerative approach is warranted to save these before-mentioned amputations. To this extent, herein, we describe the detailed methods in generating a type 1 diabetes mellitus (T1DM) condition in immunocompromised mice, inducing cutaneous wound, and application of dental pulp stem cell-derived secretory products for therapeutic assessment. This model helps in evaluating the efficacy of stem cell-based therapy and helps with the investigation of involved mechanisms in impaired cutaneous wound healing caused by hyperglycemic stress due to type 1 diabetes.


Should β blockers no longer be considered first-line therapy for the treatment of essential hypertension without comorbidities?
Although most guidelines committees historically recommended initial diuretics and/or β blockers for uncomplicated hypertension, clinical trial outcomes analyzed in the last 5 to 7 years have been suboptimal with atenolol, the world's most popular β blocker. Several meta-analyses have suggested that despite lowering blood pressure, any and all β blockers inadequately protect hypertensive patients from cardiovascular events. These phenomena have been attributed to ineffective lowering of central aortic or inter-visit blood pressures, or adverse metabolic effects (particularly when combined with diuretics). Although there has never been a head-to-head comparison of atenolol with any other β blocker in hypertensive patients, indirect comparisons can be done with network and Bayesian meta-analyses, which suggest that heterogeneity of β-blockers' pharmacology also extends to outcomes. Although once-daily atenolol as initial antihypertensive therapy may be unwise, whether initial β blockers newer than atenolol reduce cardiovascular risk to the same extent as other antihypertensive drugs should be answered with more clinical trials.


[Patch tests performed with Epidian in workers exposed to epoxy resins].
The patch tests according to the Jadassohn-Bloch's method were made with five Polish epoxy resins--"Epidian"--in 487 workers exposed to their action, and in 113 persons of the control group. The percentage of sensitized persons among 487 examined amounted to 22,8%, the results of test in the control group being negative. It has been found that particularly sensitizing action is produced by the non hardened resins (the percentage of persons sensitized in the group working at non hardened resins was 26,7, at hardening ones--2.6).


A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum.
Protein arginine methyltransferases (PRMTs) regulate many important cellular processes, such as transcription and RNA processing in model organisms but their functions in human malaria parasites are not elucidated. Here, we characterize PfPRMT5 in Plasmodium falciparum, which catalyzes symmetric dimethylation of histone H3 at R2 (H3R2me2s) and R8, and histone H4 at R3 in vitro. PfPRMT5 disruption results in asexual stage growth defects primarily due to lower invasion efficiency of the merozoites. Transcriptomic analysis reveals down-regulation of many transcripts related to invasion upon PfPRMT5 disruption, in agreement with H3R2me2s being an active chromatin mark. Genome-wide chromatin profiling detects extensive H3R2me2s marking of genes of different cellular processes, including invasion-related genes in wildtype parasites and PfPRMT5 disruption leads to the depletion of H3R2me2s. Interactome studies identify the association of PfPRMT5 with invasion-related transcriptional regulators such as AP2-I, BDP1, and GCN5. Furthermore, PfPRMT5 is associated with the RNA splicing machinery, and PfPRMT5 disruption caused substantial anomalies in RNA splicing events, including those for invasion-related genes. In summary, PfPRMT5 is critical for regulating parasite invasion and RNA splicing in this early-branching eukaryote.


Epidemiology and aetiology of heart failure.
Heart failure (HF) is a rapidly growing public health issue with an estimated prevalence of >37.7 million individuals globally. HF is a shared chronic phase of cardiac functional impairment secondary to many aetiologies, and patients with HF experience numerous symptoms that affect their quality of life, including dyspnoea, fatigue, poor exercise tolerance, and fluid retention. Although the underlying causes of HF vary according to sex, age, ethnicity, comorbidities, and environment, the majority of cases remain preventable. HF is associated with increased morbidity and mortality, and confers a substantial burden to the health-care system. HF is a leading cause of hospitalization among adults and the elderly. In the USA, the total medical costs for patients with HF are expected to rise from US$20.9 billion in 2012 to $53.1 billion by 2030. Improvements in the medical management of risk factors and HF have stabilized the incidence of this disease in many countries. In this Review, we provide an overview of the latest epidemiological data on HF, and propose future directions for reducing the ever-increasing HF burden.


Automatic and non-targeted analysis of the volatile profile of natural and alkalized cocoa powders using SBSE-GC-MS and chemometrics.
A total of 56 key volatile compounds present in natural and alkalized cocoa powders have been rapidly evaluated using a non-target approach using stir bar sorptive extraction gas chromatography mass spectrometry (SBSE-GC-MS) coupled to Parallel Factor Analysis 2 (PARAFAC2) automated in PARADISe. Principal component analysis (PCA) explained 80% of the variability of the concentration, in four PCs, which revealed specific groups of volatile characteristics. Partial least squares discriminant analysis (PLS-DA) helped to identify volatile compounds that were correlated to the different degrees of alkalization. Dynamics between compounds such as the acetophenone increasing and toluene and furfural decreasing in medium and strongly alkalized cocoas allowed its differentiation from natural cocoa samples. Thus, the proposed comprehensive analysis is a useful tool for understanding volatiles, e.g., for the quality control of cocoa powders with significant time and costs savings.


Studies on estrogen induced pituitary tumor in the rat with special reference to the relationship of the tuberoinfundibular dopamine neuron system.
Pituitary tumors were experimentally induced in female Wistar rats by repeated injections of estradiol dipropionate. The hypothalamus and pituitary tumors were studied simultaneously by fluorescence histochemistry and immunohistochemistry. The pituitary gland became larger with a concomitant increase of serum prolactin in proportion to the dose of estrogen. Estrogen-induced pituitary tumor exhibited a proliferating prolactin cells by the peroxidase immunohistochemical method. Ultramicroscopical findings showed that these tumor cells were in an extremely hyperfunctional state. The dopamine neuronal perikarya in the hypothalamic arcuate nucleus and their terminals in the external layer of the median eminence were examined by fluorescence histochemistry in the rats bearing estrogen induced pituitary tumor and it was concluded that in our experimental conditions, estrogen effected directly on pituitary rather than on the hypothalamus and consequently dopamine synthesis in the arcuate neurons and its release into portal capillaries were accelerated simultaneously in order to inhibit prolactin secretion from tumor cells.


Implementation of the Canadian Emergency Department Triage and Acuity Scale (CTAS) in an Urgent Care Center in Saudi Arabia.
The objectives of the study is to review and assess the implementation of the applied modified five-level triage and acuity scale triage system in AL-Yarmook Urgent Care Center (UCC), King Abdulaziz Residential City, Riyadh, Saudi Arabia. An observational cross-sectional study was conducted, where a data collection sheet was designed and distributed to triage nurses. The data collection was done during the triage process and was directly observed by the co-investigator. The triage system was reviewed by measuring three time intervals as quality indicators: time before triage (TBT), time before being seen by physician (TBP), and total length of stay (TLS) taking in consideration the timing of presentation and the level of triage. A total of 187 patients visiting the UCC during December 2014 were included. There was an almost equal distribution of males 98 (52 %) and females 89 (48 %) with most of the patients being in the age group of 14 years and younger (n = 85, 46 %). The visits of the patients were classified according to the level of triage from patients to be seen immediately by the physician to those who had been triaged out. Overall, 173 patients (92.5 %) were seen by the physician in a timely manner according to triage guidelines, while 14 patients (7.5 %) were not. The mean time was 5.36 min in TBT, 22.6 min in TBP, and 59 min in TLS. The median time to be seen by the physician was significantly greater (p = 0.001) for the urgent cases on the weekends (25 min; IQR, 21,30) as compared to the weekdays (17 min; IQR, 14,21). Generally, the results did not show significant increases in TBT, TBP, the number of patients not seen at the proper time, or referral and admission rates during weekends. The Canadian Emergency Department Triage and Acuity Scale (CTAS) is adaptable to countries beyond Canada and can be implemented successfully. The applied CTAS triage system in Al-Yarmouk UCC in Riyadh, Saudi Arabia, is considered to be well applied. Overall, urgent cases have been seen by physicians in a timely manner according to the triage system, and there was no delay in the management of critical cases which need prompt attention.


Protective effect of (-)-epigallocatechin-3-gallate on capsaicin-induced DNA damage and oxidative stress in human erythrocyes and leucocytes in vitro.
The aim of this study is to show that protective effects of the main catechin (-)-epigallocatechin-3-gallate (EGCG) against capsaicin (CAP) induced oxidative stress and DNA damage in human blood in vitro. Superoxide dismutase, catalase, glutathione peroxidase and malondialdehyde (MDA) level were studied in erythrocytes and leucocytes with increased concentrations of CAP. DNA damage in leucocytes was measured by the comet assay. Human blood cells have been administered with doses between 0 and 200 μM of CAP and/or EGCG (20 μM) for an hour at 37 °C. Treatment with CAP alone has increased the levels of MDA and decreased antioxidant enzymes in human blood cells. A significant increase in tail DNA%, mean tail length and tail moment indicating DNA damage has been observed at the highest dose of CAP treatment when compared to controls. Treatment of cells with CAP plus EGCG prevented CAP-induced changes in antioxidant enzyme activities and MDA level and mean tail lenght indicating DNA damage. A significant increase in mean tail lenght was observed at high doses of CAP. These data suggest that EGCG can prevent toxicity to human erythrocytes and leucocytes caused by CAP, only at low doses.


Next steps in regenerative medicine.
Pluripotent stem cells have opened the gate to cell replacement therapy. As we inch closer to clinical application, we must improve the effectiveness of cell-based therapies. I will discuss the combination of cell transplantation with gene therapy, medication, and rehabilitation to set sight on the next frontier of regenerative medicine.


Effects of Exoskeletal Lower Limb Robot Training on the Activities of Daily Living in Stroke Patients: Retrospective Pre-Post Comparison Using Propensity Score Matched Analysis.
There is limited evidence of gait training using newly developed exoskeletal lower limb robot called Hybrid Assistive Limb (HAL) on the function and ability to perform ADL in stroke patients. In clinical settings, we frequently find it challenging to conduct a randomized controlled trial; thus, a large-scale observational study using propensity score analysis methods is a feasible alternative. The present study aimed to determine whether exoskeletal lower limb robot training improved the ability to perform ADL in stroke patients. Acute stroke patients who were admitted to our facility from April 2016 to March 2017 were evaluated in the conventional rehabilitation period (CRP) and those admitted from April 2017 to June 2019 were evaluated in the HAL rehabilitation period (HRP). We started a new gait rehabilitation program using HAL at the midpoint of these two periods. The functional outcomes or ADL ability outcomes of the patients in the CRP and the subsequent HRP were compared using propensity score matched analyses. Propensity score matching analysis was performed for 108 stroke patients (63 from the CRP and 45 from the HRP), and 36 pairs were matched. The ADL ability, defined by the FIM scores and FIM score change, was significantly higher in patients admitted during the HRP. In addition, more stroke patients obtained practical walking ability during hospitalization in the HRP. Gait training using HAL affects the ADL ability and obtaining of practical walking ability of stroke patients.


Prolyl oligopeptidase inhibition ameliorates experimental pulmonary fibrosis both in vivo and in vitro.
Pulmonary fibrosis is a progressive disease characterized by lung remodeling due to excessive deposition of extracellular matrix. Although the etiology remains unknown, aberrant angiogenesis and inflammation play an important role in the development of this pathology. In this context, recent scientific research has identified new molecules involved in angiogenesis and inflammation, such as the prolyl oligopeptidase (PREP), a proteolytic enzyme belonging to the serine protease family, linked to the pathology of many lung diseases such as pulmonary fibrosis. Therefore, the aim of this study was to investigate the effect of a selective inhibitor of PREP, known as KYP-2047, in an in vitro and in an in vivo model of pulmonary fibrosis. The in vitro model was performed using human alveolar A549 cells. Cells were exposed to lipopolysaccharide (LPS) 10 μg/ml and then, cells were treated with KYP-2047 at the concentrations of 1 μM, 10 μM and 50 μM. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide colorimetric assay, while inflammatory protein expression was assessed by western blots analysis. The in vivo model was induced in mice by intra-tracheal administration of bleomycin (1 mg/kg) and then treated intraperitoneally with KYP-2047 at doses of 1, 2.5 and 5 mg/kg once daily for 12 days and then mice were sacrificed, and lung tissues were collected for analyses. The in vitro results demonstrated that KYP-2047 preserved cell viability, reduced inflammatory process by decreasing IL-18 and TNF-α, and modulated lipid peroxidation as well as nitrosative stress. The in vivo pulmonary fibrosis has demonstrated that KYP-2047 was able to restore histological alterations reducing lung injury. Our data demonstrated that KYP-2047 significantly reduced angiogenesis process and the fibrotic damage modulating the expression of fibrotic markers. Furthermore, KYP-2047 treatment modulated the IκBα/NF-κB pathway and reduced the expression of related pro-inflammatory enzymes and cytokines. Moreover, KYP-2047 was able to modulate the JAK2/STAT3 pathway, highly involved in pulmonary fibrosis. In conclusion, this study demonstrated the involvement of PREP in the pathogenesis of pulmonary fibrosis and that its inhibition by KYP-2047 has a protective role in lung injury induced by BLM, suggesting PREP as a potential target therapy for pulmonary fibrosis. These results speculate the potential protective mechanism of KYP-2047 through the modulation of JAK2/STAT3 and NF-κB pathways.


[How to communicate with families of patients in complete isolation during SARS-CoV-2 pandemic multidisciplinary working group "ComuniCoViD".]
The global emergency caused by the SARS-CoV-2 pandemic has suddenly changed how we communicate with families in all the CoViD-19 care settings, due to the obligation to maintain complete social isolation. Healthcare workers are isolated from their families, and must manage the consequences of this isolation just like the patients. They and their families perceive the personal attitudes, closeness and psychological support from the care teams. This perception of genuine participation by the healthcare workers during isolation is especially important when a patient dies, and it may influence the process of grief. This document is intended for all healthcare professionals caring for CoViD-19 patients, particularly those in more severe clinical conditions and it is aimed to help the care team to communicate with families distanced from the patient. The document consists of three parts: 1) presentation of the statements for communicating with patients family members during isolation; 2) discussion of key points as a theoretical framework for the statements; 3) instructions for telephone communication, with a checklist and a worksheet. The document was written by authors from different disciplines (doctors, nurses, psychologists, legal experts) and was then reviewed by a group of experts comprising professionals, people who have experienced ICU hospitalization, and their families. Finally, the document was approved by the National Boards of the Italian Society of Anesthesia and Intensive Care (SIAARTI), Italian Association of Critical Care Nurses (Aniarti), Italian Society of Emergency Medicine (SIMEU), and Italian Society of Palliative Care (SICP).


Mind the model: effect of instrumentation on inducibility of atrial fibrillation in a sheep model.
Atrial electrical remodeling, shortening of the atrial effective refractory period (AERP) underlying atrial fibrillation (AF) has been described in different animal models. However, there remains some controversy regarding the time course of this electrical remodeling and the need for secondary factors in the development of AF. We investigated the effect of instrumentation on the inducibility of AF. We hypothesized that epicardial instrumentation could be a confounding factor that accelerates the development of AF. Thirty sheep were rapidly atrially paced at 600 beats/min for 15 weeks: 15 were endocardially instrumented and paced (endo), and 15 were both endocardially and epicardially instrumented. Six of these animals were endocardially paced (sham) and 9 were epicardially paced (epi). The underlying rhythm was determined at regular intervals, and electrophysiologic study was performed. AF developed significantly faster in the epi group. After 3 weeks of pacing, the cumulative incidence of sustained AF (>1 hour) already was 70% in this group versus only 14% and 20% in the endo and sham groups, respectively. After 15 weeks of pacing, this difference was no longer evident. Baseline AERP and minimal AERP, reached before the development of AF, were not significantly different in the three groups. Epicardial instrumentation (epi and sham) increased baseline left and right atrial pressures, but only epicardial stimulation (epi) led to early development of AF. In this sheep model of AF, the experimental setup is a major determinant of the inducibility of AF. Not epicardial instrumentation per se but epicardial stimulation accelerated the development of AF. Different animal models


Data on soil properties and halophilic bacterial densities in the Na Si Nuan Secondary Forest at Kantharawichai District, Maha Sarakham, Thailand.
Saline soil is one of the most crucial problems of arid and semiarid regions because it reduces growth of plant and microorganisms. In Thailand, the inland saline soils are found mostly in the northeastern part especially in Maha Sarakham Province where 85% of the province has geological characteristics as rock salt beds. Saline soil often experiences low soil fertility problems which multiply the adverse effects on plant growth. Interestingly, the Na Si Nuan Secondary Forest, Kantharawichai District, Maha Sarakham, is not affected by salinity although almost the entire province of Maha Sarakham is salt-affected area. Saline soil is a habitat of halophilic bacteria. Bacteria are the most important microorganisms contribute to soil fertility and soil health. Thus data regarding the density of culturable halophilic bacteria and soil properties in this forest soil is useful for reclamation of saline soil and helping to sustain the forest ecosystem.


Ocular biometrics and uncorrected visual acuity for detecting myopia in Chinese school students.
The study is to evaluate the performance of ocular biometric measures and uncorrected visual acuity (UCVA) for detecting myopia among Chinese students. Among 5- to 18-year-old Chinese students from two cities of China, trained eye-care professionals performed assessment of ocular biometrics (axial length (AL), corneal curvature radius (CR), anterior chamber depth) under noncycloplegic conditions using NIDEK Optical Biometer AL-Scan, distance visual acuity using retro-illuminated logMAR chart with tumbling-E optotypes, and cycloplegic refractive error using NIDEK autorefractor with administration of 0.5% tropicamide. Spherical equivalent (SER) in diopters (D) was calculated as sphere plus half cylinder, and myopia was defined as SER ≤ - 0.5 D. Performances of ocular biometrics and UCVA (individually and in combination) for detecting myopia were evaluated using sensitivity and specificity, predictive values, and area under ROC curve (AUC) in both development dataset and validation dataset. Among 3436 students (mean age 9.7 years, 51% female), the mean (SD) cycloplegic SER was - 0.20 (2.18) D, and 1269 (36.9%) had myopia. Cycloplegic SER was significantly correlated with AL (Pearson Correlation coefficient r = - 0.82), AL/CR ratio (r = - 0.90), and UCVA (r = 0.79), but was not correlated with CR (r = 0.02, p = 0.15). The AL/CR ratio detected myopia with AUC 0.963 (95% CI 0.957-0.969) and combination with UCVA improved the AUC to 0.976 (95% CI 0.971-0.981). Using age-specific AL/CR cutoff (> 3.00 for age < 10 years, > 3.06 for 10-14 years, > 3.08 for ≥ 15 years) as myopia positive, the sensitivity and specificity were 87.0% (95% CI 84.4-89.6%) and 87.8% (86.0-89.6%), respectively, in the development dataset and 86.4% (95% CI 83.7-89.1%) and 89.4% (95% CI 87.3-91.4%), respectively, in the validation dataset. Combining AL/CR and UCVA (worse than 20/32 for age < 10 years, and 20/25 for ≥ 10 years) provided 91.9% (95% CI 90.4-93.4%) sensitivity and 87.0% (95% CI 85.6-88.4%) specificity, positive value of 80.6% (95% CI 78.5-82.6%) and negative value of 94.8% (95% CI 93.8-95.8%). These results suggest that AL/CR ratio is highly correlated with cycloplegic refractive error and detects myopia with high sensitivity and specificity, AL/CR ratio alone or in combination with UCVA can be used as a tool for myopia screening or for estimating myopia prevalence in large epidemiological studies with limited resources for cycloplegic refraction.


Protein Tyrosine Kinase 6 Regulates UVB-Induced Signaling and Tumorigenesis in Mouse Skin.
Protein tyrosine kinase 6 (PTK6, also called BRK) is an intracellular tyrosine kinase expressed in the epithelial linings of the gastrointestinal tract and the skin, where it is expressed in nondividing differentiated cells. We found that PTK6 expression increases in the epidermis following UVB treatment. To evaluate the roles of PTK6 in the skin following UVB-induced damage, we exposed back skin of Ptk6 +/+ and Ptk6 -/- SENCAR mice to incremental doses of UVB for 30 weeks. Wild-type mice were more sensitive to UVB and exhibited increased inflammation and greater activation of signal transducer and activator of transcription-3 (STAT3) than Ptk6-/- mice. Disruption of Ptk6 did not have an impact on proliferation, although PTK6 was expressed and activated in basal epithelial cells in wild-type mice following UVB treatment. However, wild-type mice exhibited shortened tumor latency and increased tumor load compared with Ptk6-/- mice, and STAT3 activation was increased in these tumors. PTK6 activation was detected in UVB-induced tumors, and this correlated with increased activating phosphorylation of focal adhesion kinase (FAK) and breast cancer anti-estrogen resistance 1 (BCAR1). Activation of PTK6 was also detected in human squamous cell carcinomas of the skin. Although PTK6 has roles in normal differentiation, it also contributes to UVB-induced injury and tumorigenesis in vivo.


Full genome analysis of hepatitis B virus genotype E strains from South-Western Africa and Madagascar reveals low genetic variability.
The eight genotypes of hepatitis B virus (HBV), A-H, have a characteristic geographical distribution. The high prevalence of genotype E within a wide expanse of Africa makes it important to characterize this genotype. Although the preS/S region of a large number of genotype E isolates has been sequenced, to date only eight complete genotype E genomes have been published. The aim of this study, therefore, was to sequence and characterize the complete genome of genotype E isolates obtained from geographically distinct regions in Africa, including Namibia, Angola, and Madagascar. The nine newly sequenced genotype E isolates were closely related with an intra-group nucleotide divergence of 1.2%, reflecting their close geographical origin. All genotype E strains have the same characteristics, an in-frame deletion of three nucleotides (one amino acid) in the 5' pre-S1, a signature pattern of amino acids in the pre-S1 region and the serological subtype ayw4. In addition, we have identified another unique attribute of genotype E strains, the introduction of another start codon Met(83) in the pre-S1 region that may result in the translation of an elongated middle hepatitis B surface protein (MHBs).


The incremental validity of lumbar surface EMG, behavioral observation, and a symptom checklist in the assessment of patients with chronic low-back pain.
This study evaluated the comparative ability of lumbar surface EMG, behavioral observation, and a symptom checklist to correctly classify three groups of participants, (1) 18 patients with chronic low-back pain (CLBP), demonstrating excessive and/or anatomically inconsistent motor, sensory, and tenderness responses during a neurological examination, (2) 33 patients with CLBP exhibiting few or no inconsistent responses, and (3) 30 healthy matched controls. Discriminant analyses were used to develop predictive models. Correct classification rates for the individual assessments and all combinations of assessments were contrasted. Each modality predicted group membership significantly better than weighted chance (23%), with the symptom checklist approach having the highest individual correct classification rate (64%). The best combination of modalities was the symptom checklist and lumbar surface EMG (70% correct classification rate). The sensitivity and specificity of the individual assessments and all combinations of assessments are also presented.


Patterns of oxycodone controlled release use in older people with cancer following public subsidy of oxycodone/naloxone formulations: An Australian population-based study.
Public subsidy of the oxycodone/naloxone controlled release (CR) combination in December 2011 expanded the overall market for oxycodone CR in the general public in Australia; we evaluate its impact in people with cancer. We used Repatriation Pharmaceutical Benefits dispensing data linked with the NSW Cancer Registry for Department of Veterans' Affairs (DVA) healthcare card holders 65 years and older residing in NSW between 2004 and 2013 to identify clients with cancer and their opioid dispensings. We used interrupted time series analysis to model changes in monthly rates of oxycodone CR tablets dispensed and initiations. We performed a retrospective cohort study to examine changes in client characteristics and opioid utilization over time by comparing clients initiating oxycodone CR before and after subsidy. The rate of oxycodone CR tablets dispensed/month increased by 20% from December 2011, due to uptake of the oxycodone/naloxone CR combination; monthly initiations increased immediately by 17%. Initiations of buprenorphine, fentanyl, and morphine declined from December 2011. DVA healthcare card holders were significantly more likely to initiate the 5 mg oxycodone CR formulation; more likely to use immediate release oxycodone in the 90 days following initiation; and less likely to use a weak opioid in the 90 days preceding oxycodone CR initiation following December 2011 than they were prior to that time. The public subsidy of the oxycodone/naloxone CR formulation expanded the overall oxycodone CR market for DVA healthcare card holders with cancer. Our findings highlight the need for updated guidelines around risk management for opioid treatment in patients with cancer.


Diabetes mellitus early warning and factor analysis using ensemble Bayesian networks with SMOTE-ENN and Boruta.
Diabetes mellitus (DM) has become the third chronic non-infectious disease affecting patients after tumor, cardiovascular and cerebrovascular diseases, becoming one of the major public health issues worldwide. Detection of early warning risk factors for DM is key to the prevention of DM, which has been the focus of some previous studies. Therefore, from the perspective of residents' self-management and prevention, this study constructed Bayesian networks (BNs) combining feature screening and multiple resampling techniques for DM monitoring data with a class imbalance in Shanxi Province, China, to detect risk factors in chronic disease monitoring programs and predict the risk of DM. First, univariate analysis and Boruta feature selection algorithm were employed to conduct the preliminary screening of all included risk factors. Then, three resampling techniques, SMOTE, Borderline-SMOTE (BL-SMOTE) and SMOTE-ENN, were adopted to deal with data imbalance. Finally, BNs developed by three algorithms (Tabu, Hill-climbing and MMHC) were constructed using the processed data to find the warning factors that strongly correlate with DM. The results showed that the accuracy of DM classification is significantly improved by the BNs constructed by processed data. In particular, the BNs combined with the SMOTE-ENN resampling improved the most, and the BNs constructed by the Tabu algorithm obtained the best classification performance compared with the hill-climbing and MMHC algorithms. The best-performing joint Boruta-SMOTE-ENN-Tabu model showed that the risk factors of DM included family history, age, central obesity, hyperlipidemia, salt reduction, occupation, heart rate, and BMI.


Publication bias in gastroenterological research - a retrospective cohort study based on abstracts submitted to a scientific meeting.
The aim of this study was to examine the determinants of publication and whether publication bias occurred in gastroenterological research. A random sample of abstracts submitted to DDW, the major GI meeting (1992-1995) was evaluated. The publication status was determined by database searches, complemented by a mailed survey to abstract authors. Determinants of publication were examined by Cox proportional hazards model and multiple logistic regression. The sample included abstracts on 326 controlled clinical trials (CCT), 336 other clinical research reports (OCR), and 174 basic science studies (BSS). 392 abstracts (47%) were published as full papers. Acceptance for presentation at the meeting was a strong predictor of subsequent publication for all research types (overall, 54% vs. 34%, OR 2.3, 95% CI 1.7 to 3.1). In the multivariate analysis, multi-center status was found to predict publication (OR 2.8, 95% CI 1.6-4.9). There was no significant association between direction of study results and subsequent publication. Studies were less likely to be published in high impact journals if the results were not statistically significant (OR 0.5, 95 CI 95% 0.3-0.6). The author survey identified lack of time or interest as the main reason for failure to publish. Abstracts which were selected for presentation at the DDW are more likely to be followed by full publications. The statistical significance of the study results was not found to be a predictor of publication but influences the chances for high impact publication.


Diagnostic Imaging of Diseases Affecting the Guttural Pouch.
The most common diseases of the guttural pouch are empyema, tympany, mycosis and temporohyoid osteoarthropathy. The challenge in diagnosis of guttural pouch diseases lies in the complex anatomy of the guttural pouch and adjacent associated structures. Diagnostic imaging is a good complement to endoscopy for the diagnosis of some guttural pouch diseases, especially to make a full assessment of the lesions involving the pouch and surrounding structures. This review article describes the value of each diagnostic imaging technique in the diagnosis of guttural pouch disease and the corresponding imaging findings. Radiography is generally used as the first line to complement endoscopic findings, and can give useful additional information although it is limited by superimposition. Ultrasonographic examination of the guttural pouch is of limited value due to the presence of gas in the guttural pouch but can eventually be used to detect fluid within the pouch or can help to evaluate the soft tissues located lateral and ventral to the guttural pouch. Cross-sectional imaging, especially CT, is increasingly available and appears to be the best technique to fully assess the surrounding soft tissues and to precisely identify lesions of the temporohyoid apparatus, temporal bone and skull base that are associated with guttural pouch disease.


Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety.
To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period. In all, 134 children (89 female) with various rheumatic diseases were treated with biologic agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus (12.7%) and vasculitis (4.5%). All patients received concomitant therapy (corticosteroids and disease-modifying antirheumatic drugs). In total, 273 treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47 adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept). Therapy was switched to another agent in 57 (42.5%) patients, mainly because of inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events were notified; of these, the most frequent were infusion-related reactions (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One patient developed macrophage activation syndrome. Biologic agents were used in children with a range of rheumatic diseases. Of these, the most frequent was JIA. Off-label use of biologic agents in our cohort is common. These agents seem safe. However, they may associated with various adverse events. Sequential therapy seems well tolerated. However, this should be carefully balanced and considered on an individual basis.


Recurrent pericardial effusion and tamponade after epicardial pacemaker lead placement: a case report.
Epicardial pacemaker placement is often necessary in pacemaker-dependent patients with ongoing device pocket infection or lack of venous access. Pericardial effusion and tamponade are rare but serious complications of this procedure. A 38-year-old woman presented with nausea, diaphoresis, and hypotension 7 days after epicardial lead placement. Echocardiography revealed a large pericardial effusion with signs of tamponade. Despite initial improvement after pericardiocentesis, she continued to develop symptomatic pericardial effusions. The patient ultimately underwent pleuro-pericardial window surgery, which resulted in sustained resolution of effusion recurrence. Cases of recurrent pericardial effusion and tamponade following epicardial lead placement have been reported in the literature, although they are rare. While extensive partial pericardiectomy or total pericardiectomy was required to achieve adequate control of fluid accumulation in prior case reports, our patient was successfully managed with a pleuro-pericardial window.


The effects of repeated audiogenic convulsions on the organization of sleep in rats.
The organization of sleep in Krushinskii-Molodkina rats, with an inherited predisposition to audiogenic convulsions, was studied during and after repeated audiogenic convulsions consisting of two, three, or five relatively rare (separated by intervals of 90 min) or three, five, or nine relatively frequent (separated by intervals of 45 min) generalized clonic-tonic convulsions. In rats subjected to repeated seizures with rare convulsions, behavior in the periods between individual convulsions was dominated by passive waking (75.2 +/- 4.6% of the time), with a low level (24.8 +/- 4.3%) of slow-wave and a complete absence of fast-wave sleep, i.e., there was selective removal of the fast-wave sleep phase from the sleep-waking cycle of the rats. In rats subjected to frequent seizures with frequent convulsions, the period between convulsions showed only passive waking, with complete loss of slow-wave and fast-wave sleep, i.e., total sleep deprivation took place. The minimal latent period before the appearance of the first episodes of slow-wave sleep after repeated convulsions was 59.9 +/- 10.8 min; that for fast-wave sleep was 158.2 +/- 13.4 min. However, the first episodes of slow-wave and fast-wave sleep had an essentially normal structure, though episodes shorter than those in controls were seen, albeit more rarely. Despite the prolonged (up to 7 h) absence of slow-wave sleep during seizures and the prolonged (8.5 h) decrease in fast-wave sleep, there was no compensatory increase in the levels of these states in the sleep-waking cycle during the 12 h of recovery after seizures. Overall, the recovery period after repeated seizures was characterized by an increase (compared with controls) in the total proportion of waking in the behavior of the rats, with a decrease in the total duration of slow-wave and fast-wave sleep. It is concluded that the paroxysmal status significantly disorganizes the operation of the sleep-generating structures of the brain. The functioning of the systems responsible for slow-wave sleep is less affected, while impairments of the activity of the systems responsible for the formation of fast-wave sleep are more significant, affecting primarily the mechanisms triggering this sleep phase.


Invasive group A streptococcal disease: should close contacts routinely receive antibiotic prophylaxis?
Group A streptococci (Streptococcus pyogenes) causes a wide range of illnesses from non-invasive disease--eg, pharyngitis--to more severe invasive infections--eg, necrotising fasciitis and toxic shock-like syndrome. There remains uncertainty about the risk of secondary cases of invasive disease occurring among close contacts of an index case and how best to manage that risk. We do not consider that currently available evidence justifies the routine administration of chemoprophylaxis to close contacts. We suggest that the appropriate response should be to routinely inform all household contacts of a patient with invasive group A streptococcal disease about the clinical manifestations of invasive disease and to seek immediate medical attention if they develop such symptoms.


A topology-based method to mitigate the dosimetric uncertainty caused by the positional variation of the boost volume in breast conservative radiotherapy.
To improve local control rate in patients with breast cancer receiving adjuvant radiotherapy after breast conservative surgery, additional boost dose to the tumor bed could be delivered simultaneously via the simultaneous integrated boost (SIB) modulated technique. However, the position of tumor bed kept changing during the treatment course as the treatment position was aligned to bony anatomy. This study aimed to analyze the positional uncertainties between bony anatomy and tumor bed, and a topology-based approach was derived to stratify patients with high variation in tumor bed localization. Sixty patients with early-stage breast cancer or ductal carcinoma in situ were enrolled. All received adjuvant whole breast radiotherapy with or without local boost via SIB technique. The delineation of tumor bed was defined by incorporating the anatomy of seroma, adjacent surgical clips, and any architectural distortion on computed tomography simulation. A total of 1740 on-board images were retrospectively analyzed. Positional uncertainty of tumor bed was assessed by four components: namely systematic error (SE), and random error (RE), through anterior-posterior (AP), cranial-caudal (CC), left-right (LR) directions and couch rotation (CR). Age, tumor location, and body-mass factors including volume of breast, volume of tumor bed, breast thickness, and body mass index (BMI) were analyzed for their predictive role. The appropriate margin to accommodate the positional uncertainty of the boost volume was assessed, and the new plans with this margin for the tumor bed was designed as the high risk planning target volume (PTV-H) were created retrospectively to evaluate the impact on organs at risk. In univariate analysis, a larger breast thickness, larger breast volume, higher BMI, and different tumor locations correlated with a greater positional uncertainty of tumor bed. However, BMI was the only factor associated with displacements of surgical clips in the multivariate analysis and patients with higher BMI were stratified as high variation group. When image guidance was aligned to bony structures, the SE and RE of clip displacement were consistently larger in the high variation group. The corresponding PTV-H margins for the high- and low-variation groups were 7, 10, 10 mm and 4, 9, 6 mm in AP, CC, LR directions, respectively. The heart dose between the two plans was not significantly different, whereas the dosimetric parameters for the ipsilateral lung were generally higher in the new plans. In patients with breast cancer receiving adjuvant radiotherapy, a higher BMI is associated with a greater positional uncertainty of the boost tumor volume. More generous margin should be considered and it can be safely applied through proper design of beam arrangement with advanced treatment techniques.


The Relative Merits of Direct Angioplasty versus Intravenous Thrombolytic Therapy for the Treatment of Acute Myocardial Infarction.
There is growing interest in the use of angioplasty as the primary method to achieve coronary artery reperfusion in patients with acute myocardial infarction. The use of thrombolytic therapy has been established as effective in many large clinical trials, while only a few small studies have been completed comparing primary angioplasty with thrombolytic therapy. This paper briefly compares the use of these two treatment modalities and concludes that primary angioplasty is the preferred approach in patients with cardiogenic shock and for those patients with large myocardial infarctions who have contraindications to thrombolytic therapy. Other patients with AMI should receive thrombolytic therapy unless there are contraindications to this treatment.


Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease.
The relationship between severity and zonal location of steatosis and the presence of steatohepatitis and various histological features that define NASH has not been formally studied. We conducted a study to examine the relationship of severity and zonal location of steatosis to the presence of NASH and to other histological features that define NASH in adult patients with NAFLD. Steatosis was graded as mild, moderate or severe. We examined the relationship between severity and zonal location of steatosis and the following: lobular inflammation, presence of ballooning, Mallory bodies, fibrosis score, and definite steatohepatitis. Mild, moderate and severe steatosis was present in 44%, 31% and 25% of biopsies, respectively. Definite steatohepatitis was present in 59% and advanced fibrosis in 29% of liver biopsies. Increasing levels of steatosis severity were positively associated with lobular inflammation (p<0.0001), zone 3 fibrosis (p<0.001), and definite steatohepatitis (p=0.02), but were unrelated to ballooning, Mallory bodies, or advanced fibrosis. As compared to zone 3 steatosis, pan-acinar steatosis was more often associated with ballooning, Mallory bodies, and advanced fibrosis. Patients with severe steatosis are more likely to have steatohepatitis. More studies are needed to confirm this observation and to explore its significance.


Right sided heart failure secondary to hypereosinophilic cardiomyopathy - clinical manifestation and diagnostic pathway.
Hypereosinophilic cardiomyopathy is a rare restrictive cardiomyopathy which often presents with left-sided heart failure. We present an interesting case of a 58-year-old male patient with known hypereosinophillic syndrome who had presented with congestive cardiac failure with predominant features of right-sided volume overload. Cardiac magnetic resonance imaging confirmed the diagnosis by demonstrating obliteration of the right ventricular apex and endocardial-delayed gadolinium enhancement at the mid-septal and inferior segment, at both the right ventricular and left ventricular apical region, consistent with fibrosis. He was successfully treated with intravenous diuretics to good effect. This case report demonstrates a rare clinical presentation of right ventricle involvement in hypereosinophilic cardiomyopathy and the current pathway for diagnosis with the favoured emergence of cardiac magnetic resonance imaging. All patients with hypereosinophilic syndrome should be closely monitored for signs of cardiac involvement, as early treatment carries a better prognosis.


H-2 control of polyadenylated mRNA production in the spleen of mice injected with Brucella antigens.
RNA was extracted from the splenocytes of Brucella abortus antigen stimulated mice and of control mice. The proportion of chromatographically separated polyadenylated 11.2S mRNA, was determined. With the technique used, only stimulated mice exhibited significant amounts of this RNA species. The highest level was reached 1 day after the stimulation, and the decay from this level presented an oscillatory form during the 4 weeks following the injection. In two different genetic backgrounds, H-2b mice did not respond to the stimulus, in contrast to H-2a and H-2f mice. H-2b/H-2f heterozygotes behaved roughly as intermediate between H-2b and H-2f mice. This genetic control seems to parallel the genetic control of some Brucella-induced, thymus-dependent events previously described.


Rehabilitation outcomes in females with spinal cord injury: a follow-up study.
A follow-up study was carried out on patients with spinal cord injury discharged from the G. F. Strong Rehabilitation Centre, Vancouver, British Columbia, Canada over a five year period with a minimum time from discharge to follow up of 18 months. Those no longer residing in the province, under the age of sixteen years on discharge, or who had made a substantial recovery were eliminated from the study. All of the patients included required a wheelchair or other aids for ambulation and had loss of normal bowel and bladder control. Twenty-four patients out of 37 who met the criteria were interviewed and details of medical, social, vocational and psychological outcomes are presented. In addition there were four deaths, the causes of which are discussed. Interesting comparisons between tetraplegic and paraplegic patients are given. Some differences between the findings in female and male patients are included.


Experimental retinal autoimmunity (ERA) in strain 13 guinea pigs: induction of ERA-retinopathy with rhodopsin.
Strain 13 guinea pigs injected with either homologous or bovine rhodopsin, the visual pigment of the retinal outer segments, in complete Freund's adjuvant (CFA) developed experimental retinal autoimmunity (ERA). Initial clinical signs of disease were seen within 21 days after immunization. Pathologic examination of the eyes revealed the presence of inflammatory cells in the choroid and the destruction of the retinal rod outer segments. The unique feature of this disease is that despite the destruction of the inner and outer segments of the retina, at no time is there a substantial inflammatory cell infiltrate. Even as late as 45 days after immunization, when destruction of the retinal ganglion cell layer was noted, no inflammatory cells were detected in the retina. These findings suggest that the retinal inner and outer segments are the target of the autoimmune reaction subsequent to sensitization with purified rhodopsin-CFA.


Generalization of cognitive training in an Australian sample of schizophrenia patients.
The present study was undertaken to evaluate the effect of cognitive training in improving trained and untrained cognitive processes in schizophrenia. A simple pre- and post experimental study with a three month follow-up was conducted to determine the efficacy of cognitive training in speed of processing and executive functions improving cognition in 22 schizophrenia patients. Significant improvement was found in those cognitive domains specifically targeted in the training protocol, but also to a limited extent on verbal memory and social cognition. There was also evidence of improvements in symptoms and social functioning. The training effects failed to transfer to community functioning skills however. Except for social cognition, these improvements were maintained at 3month follow-up. The study highlights the importance of understanding the mechanisms that contribute to the transfer of skills as well as the maintenance of cognitive changes in individuals with schizophrenia.


Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging.
Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy-Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.


Treatment with pimecrolimus cream 1% clears irritant dermatitis of the periocular region, face and neck.
Irritant dermatitis of the face and neck is particularly prevalent in women > or = 30 years old, who typically present with periocular cutaneous symptoms. Current therapies are limited, indicating a need for rapid, effective alternatives. Pimecrolimus cream 1%, a nonsteroid, cell-selective inhibitor of inflammatory-cytokine release, is effective in the treatment of inflammatory skin diseases, such as chronic irritant dermatitis of the hands, and thus offers a potential therapeutic option for this indication. This study reports on the safety and efficacy of pimecrolimus treatment in patients with irritant periocular dermatitis, extending to the face and neck in some patients. Twenty-seven patients with periocular irritant dermatitis (extending onto the face and neck in eight) were treated twice daily with pimecrolimus cream 1% for 7 d, followed by once-daily application for a further 7 d. Erythema, swelling, and pruritus were assessed at baseline, weeks 1-4 using a 4-point clinical score (0, absent; 1, mild; 2, moderate; and 3, severe). All patients showed marked improvement within 2-3 d of treatment with disease clearance in 23 of 27 patients within 14 d. In the remaining four patients, mild relapse occurred at weeks 3-4, but improvement was observed following a further 10-d treatment. Side-effects were mild and transient. Pimecrolimus cream 1% provides a new potential option for treatment of irritant dermatitis of the periocular region, head and neck. Further double-blind, controlled studies are required to confirm the efficacy and safety of pimecrolimus cream 1% for this indication.


HGF and bFGF Secreted by Adipose-Derived Mesenchymal Stem Cells Revert the Fibroblast Phenotype Caused by Vocal Fold Injury in a Rat Model.
To investigate how adipose-derived mesenchymal stem cells (ADSCs), secreted hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) affect the fibroblast phenotype after vocal fold injury. We cultured primary normal (uninjured) and injured vocal fold fibroblasts (VFFs). A transwell co-culture system of ADSCs and injured VFFs was constructed in vitro, then the effects of HGF or bFGF were inhibited. The proliferation, extracellular matrix (ECM) secretion and transformation of VFFs were observed. Compared with uninjured VFFs, the secretion of collagen by injured VFFs increased significantly, hyaluronan synthase 1 (HAS1) secretion decreased, and VFF transformation increased significantly. After co-culture with ADSCs, the proliferation of VFFs was accelerated and the transformation was inhibited. Co-culture inhibited the expression of type I and III collagen and promoted the expression of HAS1. When HGF or bFGF secretion was inhibited, the proliferation of injured VFFs was inhibited. The inhibitory effect on collagen was reduced by both groups, but this was more obvious with the anti-HGF group. The anti-bFGF group had a more prominent effect on HAS1 secretion after injury than the anti-HGF group but the difference was not statistically significant. The inhibition of the transformation of injured VFFs was reduced while α-smooth muscle actin was upregulated, which was more obvious with the anti-HGF group. ADSCs and secreted HGF and bFGF can revert the fibroblast phenotype caused by vocal fold injury. The effects of HGF are more significant than bFGF on collagen secretion and the transformation of VFFs into myofibroblasts. However, bFGF is more effective than HGF in upregulating HAS1.


Fathers and Asthma Care: Paternal Involvement, Beliefs, and Management Skills.
To compare asthma care roles of maternal and paternal caregivers, and examine associations between caregiver involvement and the outcomes of adherence, morbidity, and parental quality of life (QoL). Mothers and fathers in 63 families of children, ages 5-9 years, with persistent asthma completed semistructured interviews and questionnaires. Adherence was measured via electronic monitoring. Paired t tests compared parental asthma care roles, and analysis of covariance, controlling for socioeconomic status, evaluated associations of asthma outcomes with caregiver involvement scores. Mothers had higher scores on measures of involvement, beliefs in medication necessity, and on four subscales of the Family Asthma Management System Scale interview (Asthma Knowledge, Relationship with Provider, Symptom Assessment, and Response to Symptoms). Maternal QoL was lowest when both maternal and paternal involvement was high. Paternal involvement was associated with increased morbidity. There is room for enhancement of fathers' asthma care roles. Higher levels of paternal involvement may be driven by family need.


Cognitive Functioning and Health in Hispanic/Latina Breast Cancer Survivors.
We examined the effect of waist-to-hip ratio, body mass index (BMI), diet, and physical activity on cognitive functioning among Hispanic/Latina breast cancer survivors in a cross-sectional design study. Participants were 54 Hispanic/Latina breast cancer survivors and completed the NIH Toolbox Cognition Battery. Linear Regression Models tested if statistically significant correlations held with covariates. After controlling for covariates, moderate and hard physical activity were not associated with cognition. However, very hard physical activity was positively associated with faster processing speed (β = 0.56, p < 0.001) and composite cognition score (β = 0.36, p < 0.05). Total time (minutes) of moderate to very hard physical activity was positively associated with cognitive flexibility (β = 0.52, p < 0.001). Total caloric intake was positively associated with episodic memory (β = 0.35 p < 0.05). BMI and WHR were not associated with cognition. These findings showed positive association with engagement in more MVPA and harder intensity physical activity to better cognitive functioning among Hispanic/Latina breast cancer survivors.ClinicalTrials.gov NCT02780271.


Heat shock transcription factor 1 inhibits H₂O₂-induced cardiomyocyte death through suppression of high-mobility group box 1.
Heat shock transcription factor 1 (HSF1), which has been identified as an endogenous cardioprotective factor, possesses considerable anti-inflammatory effects and the ability against oxidative stress. However, the mechanisms have not been fully characterized yet. In this study, we investigated the effects of HSF1-regulated HMGB1 on cardiomyocyte death. Cultured cardiomyocytes were transfected with empty vector or HSF1 plasmid before the exposure to H(2)O(2). Cell death was assessed by cell staining. Additionally, the levels of intracellular and extracellular HMGB1 as well as its subcellular location were detected, and the expression of heat shock proteins (HSP27 and HSP90) in the cardiomyocytes was also determined. Not only did H(2)O(2) significantly increase cell death, but also elevated the levels of intracellular and extracellular HMGB1 and induced its translocation, whereas, as expected, HSF1 overexpression effectively attenuated cell death. Furthermore, HSF1 inhibited the intracellular expression of HMGB1 at early stage of oxidative stress and subsequently, HSF1 did negatively regulate the extracellular levels and the translocation of HMGB1 at late stage. Besides, the expression of HSP27 and HSP90 was significantly increased. These results suggested HSF1-attenuated cardiomyocyte death via reducing intracellular and extracellular levels of HMGB1 as well as preventing its translocation, which was partially associated with HSP27 and HSP90 up-regulated by HSF1 overexpression.


Selective and synergistic cobalt(III)-catalyzed three-component C-H bond addition to dienes and aldehydes.
Two-component C-H bond additions to a large variety of coupling partners have been developed with applications towards materials, natural product and drug synthesis. Sequential three-component C-H bond addition across two different coupling partners potentially enables the convergent synthesis of complex molecular scaffolds from simple precursors. Here, we report three-component Co(III)-catalyzed C-H bond additions to dienes and aldehydes that proceeds with high regio- and stereoselectivity resulting in two new carbon-carbon σ-bonds and from four to six new stereocenters. The reaction relies on the synergistic reactivity of the diene and aldehyde with neither undergoing C-H bond addition alone. A detailed mechanism is supported by X-ray structural characterization of a Co(III)-allyl intermediate, observed transfer of stereochemical information, and kinetic isotope studies. The applicability of the method to biologically relevant molecules is exemplified by the rapid synthesis of the western fragment of the complex ionophore antibiotic lasalocid A.


Induction by pathogen, salt and drought of a basic class II chitinase mRNA and its in situ localization in pepper (Capsicum annuum).
Northern blot and in situ hybridization analyses revealed that a pepper basic class II chitinase gene (CAChi2) is constitutively expressed in floral organs and root endodermis, but not in leaf, stem and fruit of pepper. Resistance of pepper leaves to Colletotrichum coccodes infection at a late growth stage was correlated with induction of beta-1,3-glucanase and PR-1 mRNA, but not of chitinase (CAChi2) mRNA. Transcriptional activation of the CAChi2 gene in pepper leaves occurred during anthracnose development. The CAChi2 transcripts were mainly localized in phloem cells of vascular tissues of pepper leaves infected with C. coccodes. The CAChi2 gene was also differentially induced in leaf and stem tissue by treatment with abscisic acid (ABA), sodium chloride or drought. Strong accumulation of the CAChi2 transcripts occurred in pepper stem tissues due to high salt and drought, and also due to treatment with ABA. These results suggest involvement of the chitinase gene in protection of pepper plants against the pathogen, but also document cross talk with stress signals mediated by ABA, high salinity and drought.


Maternal dietary B vitamin intake, other than folate, and the association with orofacial cleft in the offspring.
Periconceptional folic acid supplementation is suggested to prevent orofacial clefts (OFCs). Other B vitamins however may be beneficial as well. To investigate the maternal periconceptional dietary intake of thiamine, riboflavin, niacin, pyridoxine and cobalamin in association with the occurrence of OFC. Two hundred and six mothers of a child with nonsyndromic OFC and 203 control mothers filled out a general questionnaire and a food frequency questionnaire around 14 months postpartum as a proxy for periconceptional intake. After exclusion of known pregnant and lactating mothers, those who reported to have altered their diet compared to the periconceptional period, and mothers with incidental folic acid supplement use periconceptionally, data of 182 OFC mothers and 173 controls were analysed. After logarithmic transformation, geometric means (P5-P95) were calculated and compared between the groups. After subsequent adjustment for energy, quintiles of dietary B vitamin intake were created. The periconceptional intake of thiamine, niacin and pyridoxine was significantly lower in mothers of an OFC child. A trend towards risk reduction for OFC with increasing dietary intake was demonstrated for thiamine (p = 0.04) and pyridoxine (p = 0.03). Risk reductions were only demonstrated in women using folic acid supplements periconceptionally. Supplement users tended to consume a diet richer in B vitamins. Periconceptional intake of thiamine, niacin and pyridoxine seems to contribute to the prevention of OFC.


Modeling paradigms for medical diagnostic decision support: a survey and future directions.
Use of computer based decision tools to aid clinical decision making, has been a primary goal of research in biomedical informatics. Research in the last five decades has led to the development of Medical Decision Support (MDS) applications using a variety of modeling techniques, for a diverse range of medical decision problems. This paper surveys literature on modeling techniques for diagnostic decision support, with a focus on decision accuracy. Trends and shortcomings of research in this area are discussed and future directions are provided. The authors suggest that-(i) Improvement in the accuracy of MDS application may be possible by modeling of vague and temporal data, research on inference algorithms, integration of patient information from diverse sources and improvement in gene profiling algorithms; (ii) MDS research would be facilitated by public release of de-identified medical datasets, and development of opensource data-mining tool kits; (iii) Comparative evaluations of different modeling techniques are required to understand characteristics of the techniques, which can guide developers in choice of technique for a particular medical decision problem; and (iv) Evaluations of MDS applications in clinical setting are necessary to foster physicians' utilization of these decision aids.


The "dysharmonic luteal phase" syndrome: endometrial progesterone receptor and estradiol dehydrogenase.
The dysharmonic luteal phase (DLP) syndrome is defined by delayed endometrial maturation despite normal plasma progesterone (P) values. In ten patients with DLP the actual date of the endometrial biopsy, dated retrospectively, was 24.7 +/- 2.3 days, whereas the histologic date was 20.0 +/- 2.6 days. The concentration of cytosolic P receptor in DLP endometrium tended to be lower, whereas the concentration of nuclear receptor was significantly higher in DLP than in seven matched patients with normal luteal phases. Endometrial estradiol-dehydrogenase activities were identical in both groups. The DLP syndrome cannot be explained by a decreased sensitivity of the endometrium to P and is probably merely functional in nature.


Biosynthesis of heme in mammals.
Most iron in mammalian systems is routed to mitochondria to serve as a substrate for ferrochelatase. Ferrochelatase inserts iron into protoporphyrin IX to form heme which is incorporated into hemoglobin and cytochromes, the dominant hemoproteins in mammals. Tissue-specific regulatory features characterize the heme biosynthetic pathway. In erythroid cells, regulation is mediated by erythroid-specific transcription factors and the availability of iron as Fe/S clusters. In non-erythroid cells the pathway is regulated by heme-mediated feedback inhibition. All of the enzymes in the heme biosynthetic pathway have been crystallized and the crystal structures have permitted detailed analyses of enzyme mechanisms. All of the genes encoding the heme biosynthetic enzymes have been cloned and mutations of these genes are responsible for a group of human disorders designated the porphyrias and for X-linked sideroblastic anemia. The biochemistry, structural biology and the mechanisms of tissue-specific regulation are presented in this review along with the key features of the porphyric disorders.


Concepts for critical organ dosimetry in three-dimensional image-based breast brachytherapy.
To investigate dose-volume histogram (DVH) parameters for organs at risk (OARs) in sectional three-dimensional image-based accelerated partial breast irradiation. Skin, lung, and ribs were defined as OARs and the heart was discussed. Two different skin-contouring methods were tested on phantom before applying to the patient cohort. First, an inside skin wall contour was delineated with three different wall thicknesses to demonstrate the influence of contouring on DVH parameter. Second a structure was defined, delineated outside of the phantom surface, such that a three-dimensional skin volume was extended like a virtual bolus contour. Point dose values and DVH parameters were reported for 25 patient cases. The DVH parameters D0.1 cc = 65+/-21, D1 cc = 45+/-8, and D10 cc = 30+/-4 cGy/pulse for the outside skin structure around the breast corresponded to skin surface areas of 1+/-1, 6+/-3, and 6+/-11cm2. Lung volume receiving 20 Gyalphabeta3 was 8.3+/-11cm3. D0.1 cc and D2 cc in the most exposed rib were 0.7+/-0.3 and 0.4+/-0.2 Gy/pulse, respectively. In accelerated partial breast irradiation treatment planning, dose to OAR can be reported in a more sophisticated way with DVH parameters than using points only. The suggested method of skin delineation using the defined outside structure allows calculating reliable and reproducible DVH parameters.


Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma.
To investigate the biological roles and underlying molecular mechanisms of long non-coding RNA (lncRNA) PVT1 in Hepatocellular carcinoma (HCC). qRT-PCR was performed to measure the expression of miRNA and mRNA. Western blot was performed to measure the protein expression. CCK-8 assay was performed to determine cell proliferation. Flow cytometry was performed to detect cell apoptosis. Wounding-healing assay and Transwell assay was performed to detect cell migration and invasion. Dual luciferase reporter assay was performed to verify the target relationship. Quantichrom iron assay was performed to check uptake level of cellular iron. PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. In addition, the expression of miR-150 was down-regulated, while the expression of HIG2 was up-regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could partly reverse the biological effects of PVT1 knockdown on proliferation, motility, apoptosis and iron metabolism in vitro, which might be associated with dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed tumorigenesis and iron metabolism disorder by regulating the expression of miR-150 and HIG2. Taken together, the present study demonstrates that PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and provide potential therapeutic targets for HCC.


Neurology practice and stroke services across East China: a multi-site, county-level hospital-based survey.
Neurological disorders are an economic and public health burden which requires efficient and adequate medical resources. Currently, little is known about the status of the quality of neurological care services available in China. As neurological primary care is mostly provided at the county hospital level, investigation of this geographical level is required. The aim of this study is to evaluate currently available neurology care services in Yangtze River Delta Urban Agglomerations in east China. A multi-site, county-level hospital-based observational survey was conducted in east China from January 2017 to December 2017. A questionnaire was made to assess hospital and the departmental patient care capabilities, human resources and technical capacity in neurology departments. Of 228 hospitals across the Yangtze River Delta Urban Agglomerations, 217 documents were returned. Of these, 22 were excluded due to invalid hospital information or duplicate submission. Overall, most hospitals have neurology departments (162, 83.1%) while less than half of the hospitals have a stroke center (80, 41.0%) and neurology emergency department (46, 23.6%). Among 162 hospitals with neurology department, 5 were excluded due to inadequate sharing, leaving 157 hospitals for analysis. About 84.1% of these neurology departments can administer intravenous thrombolysis while about one third of them has the ability to perform arterial thrombectomy (36.9%). In addition, 46.2% of hospitals can carry out computed tomography angiography (CTA) in emergency room. Tertiary care hospitals are much more equipped with modern medical resources compared to the secondary hospitals. In four administrative regions, the neurology services are better in more economically advanced regions. Neurological care services need to be enhanced at the county-level hospitals to improve health care delivery.


A comparison of two procedures to estimate three basic monitoring landscape metrics for monitoring.
An interesting alternative to wall-to-wall mapping approaches for the estimation of landscape metrics is to use sampling. Sample-based approaches are cost-efficient, and measurement errors can be reduced considerably. The previous efforts of sample-based estimation of landscape metrics have mainly been focused on data collection methods, but in this study, we consider two estimation procedures. First, landscape metrics of interest are calculated separately for each sampled image and then the image values are averaged to obtain an estimate of the entire landscape (separated procedure, SP). Second, metric components are calculated in all sampled images and then the aggregated values are inserted into the landscape metric formulas (aggregated procedure, AP). The national land cover map (NLCM) of Sweden, reflecting the status of land cover in the year 2000, was used to provide population information to investigate the statistical performance of the estimation procedures. For this purpose, sampling simulation with a large number of replications was used. For all three landscape metrics, the second procedure (AP) produced a lower relative RMSE and bias than the first one (SP). A smaller sample unit size (50 ha) produced larger bias than a larger one (100 ha), whereas a smaller sample unit size produced a lower variance than a larger sample unit. The efficiency of a metric estimator is highly related to the degree of landscape fragmentation and the selected procedure. Incorporating information from all of the sampled images into a single one (aggregated procedure, AP) is one way to improve the statistical performance of estimators.


Aplastic anaemia. Histological investigation of methacrylate embedded bone marrow biopsy specimens; correlation with survival after conventional treatment in 15 adult patients.
Aplastic anaemia is a rare disease with a poor prognosis: 40% of the patients die within 6 months after diagnosis. The clinical condition and laboratory data show only a poor correlation with the chance of survival for longer than 6 months. Conventional bone marrow biopsy investigations did not have any predictive value, but methyl-methacrylate embedded biopsy material from 15 patients given only supportive care showed histological features considered important for the assessment of the prognosis. In 3 micron methacrylate sections non-myeloid cells, like lymphocytes, could be readily distinguished from erythropoietic cells. Three types of inflammatory infiltrate were easily distinguished according to amount and distribution. Seven of the eight patients with marked infiltration (Grade III) died within 6 months after biopsy, but none of the patients with a sparse infiltrate (Grade I), including five patients in remission. In six of 10 patients, who were not in remission, histological data permitted correction of the clinically estimated prognosis.


Biliary complications associated with selective internal radiation (SIR) therapy for unresectable liver malignancies.
Selective internal radiation (SIR) therapy using 90yttrium microspheres is effective for treating selected cases of unresectable liver malignancies with little morbidity. We herein report two cases illustrating a very rare complication of SIR. A 68-year-old patient with inoperable recurrent hepatocellular carcinoma received one treatment of SIR with 90yttrium microspheres and 4 months later presented with obstructive jaundice. Percutaneous transhepatic cholangiography revealed diffusely dilated intrahepatic ducts with multiple biliary strictures. Hepatic angiography showed normal hepatic arterial branches with no evidence of vascular insufficiency. Liver biopsy finally revealed cholestasis, cholangitis, and fibrosis, consistent with radiation-induced damage. Another 56-year-old patient with unresectable colorectal liver metastases presented with cholangitis 4 weeks after SIR. Ultrasonography showed no biliary dilatation, and endoscopic retrograde cholangiopancreatography demonstrated a normal biliary tree. Liver biopsy subsequently confirmed radiation-induced cholangitis.


Comparison of the repeatability of GABA-edited magnetic resonance spectroscopy with and without macromolecule suppression.
The inhibitory neurotransmitter γ-aminobutyric acid (GABA) can be measured in vivo using edited magnetic resonance spectroscopy (MRS), but quantification suffers from contamination by macromolecules (MM). It is possible to suppress this contamination using symmetric editing, but this procedure potentially compromises reliability of the GABA measurement. The aim of this study was to compare the repeatability of GABA-edited MRS with and without MM suppression. GABA' (non-MM contaminated) and GABA'+MM (MM-contaminated) concentration was measured in the occipital lobe (OCC) and anterior cingulate (AC) using symmetric and standard editing (n = 15). Each method was performed twice in each region. Within-participant coefficients of variation for each technique were 4.0% (GABA'+MM) and 8.6% (GABA') in the OCC and 14.8% (GABA'+MM) and 12.6% (GABA') in the AC. Intraclass correlation coefficients were better for the suppression method than standard editing in both the OCC (0.72 versus 0.67) and AC (0.41 versus 0.16). These findings were replicated in the OCC of a second cohort (n = 15). Symmetric suppression is shown to be comparable in repeatability to standard GABA-editing. Measuring a purer quantification of GABA becomes increasingly important as more research is conducted on links between GABA concentration, pathology and healthy behavior.


Effects of resection thickness on mechanics of resurfaced patellae.
Patellar resection thickness during total knee replacement (TKR) has been cited as a contributor to patellar fracture, anterior knee pain and quadriceps efficiency; however, optimal thickness required to minimize clinical complications remains unclear. The objectives of the current study were to determine how patellar resection thickness and bone quality impacts patellar bone strain, kinematics, and quadriceps efficiency. A series of specimen-specific finite element models of the knee joint with distributed patellar bone material properties were developed. Each specimen was virtually implanted with a TKR system. Each specimen was analyzed with patellar bone resected to thicknesses which varied from 9 to 14 mm. Simulations with reduced modulus bone were also performed. Each model perturbation was evaluated during a dynamic squat cycle, and bone strain, quadriceps force and six-degree-of-freedom kinematics were predicted. Highest peak bone strain was predicted in the thinnest patellae, indicating greatest risk of patellar fracture; highest median bone strain was predicted in the thickest patellae. Consistent differences in quadriceps efficiency were predicted; in early flexion the thickest patellae required the least quadriceps force. Greater sagittal plane tilt was observed for the thinnest patellae. Reduced modulus models (50% lower modulus) demonstrated an increase in peak bone strain of up to seven times the original modulus models. Understanding the complex interactions between patellar resection thickness, muscle requirements, kinematics, bone quality, and bone property distribution may aid in developing an understanding of which patients are most at risk from patellar fracture and anterior knee pain and how best to treat individuals to reduce potential complications.


The inhibitory effect of a combination of imidacloprid and permethrin on blood feeding by mosquitoes in dogs raised under outdoor conditions.
Combinations of imidacloprid and permethrin were frequently used to control harmful arthropod of companion animals. The inhibitory effects on blood-feeding activity of mosquitoes in dogs raised under outdoor conditions were evaluated by using combination of 10% (w/v) of imidacloprid and 50% (w/v) of permethrin as spot-on form. Dogs in the treated group received the combination imidacloprid/permethrin spot-on. After treatment, dogs in the control and treated groups were kept separately from the evening (17:00) to the morning of the following day (09:00) in two different kennels installed outdoors to mimic realistic dog-raising conditions. Mosquitoes in the kennels were collected by light traps placed in the kennels and a sweep net to determine evidence of blood feeding, and for species identification. Mosquitoes were collected at Days 5, 3 and 1 before agent treatment, and the Day of treatment, and Days 3, 7, 14, 21, 28, 35 and 42 after treatment. The percentages of blood-fed mosquitoes measured at Days 0, 3, 21, 28 and 42 after treatment were statistically significantly lower (p<0.01) in the treated group than in the control group. The most commonly collected mosquito, Culex tritaeniorhynchus, revealed statistically significant lower percentages (p<0.01) of blood-fed mosquitoes in the treated group than in the control group at the Day of treatment, and Days 3, 7, 21, 28 and 42 after treatment. It appeared that the test agent was effective in inhibiting blood feeding by adult female mosquitoes, and the efficacy lasts for 42 days after treatment under outdoor conditions.


[Pipamperone and the treatment of impulsive aggressive behaviour].
Pipamperone is prescribed to prevent impulsive aggressive behaviour in patients with intermittent explosive disorder, personality disorders or mental retardation. To investigate the scientific basis of this treatment. Various databases were searched using the terms 'pipamperon', 'pipamperone' and 'Dipiperon'. Located articles were reviewed in order to discover whether they dealt with the relationship between the drug and impulsiveness and aggression. results Six publications were found, all dating from before 1979. In view of the limited amount of research on the subject and the adverse side effects it is concluded that pipamperone is not the drug of first choice considering the treatment of impulsive aggressive behaviour.


Application of a polymerase chain reaction enzyme immunoassay in peripheral whole blood and serum specimens for diagnosis of acute human brucellosis.
A simple polymerase chain reaction-enzyme immunoassay (PCR-EIA) was employed for the rapid laboratory diagnosis of human brucellosis directly from peripheral blood. Whole blood and serum specimens were collected from 243 patients with acute brucellosis as determined by blood culture, serological tests, and the patients' clinical characteristics and from a control group of 50 healthy individuals. Diagnosis of brucellosis was established in 179 cases by isolation of Brucella spp. in blood culture and in 64 cases by clinical signs and serological investigation. Following the amplification of a 223-bp sequence of a gene that codes for the synthesis of an immunogenic membrane protein specific for the Brucella genus, the amplified product was detected in a microtiter plate by hybridization. Two hundred forty-one of the 243 patients tested had detectable Brucella DNA in either whole blood or serum specimens: 149 (61.3%) patients were positive in both whole blood and serum specimens, 43 (17.7%) were positive in serum specimens only, and 49 (20.2%) were positive in whole blood specimens only. The diagnostic specificity of the PCR-EIA assay for both specimen categories was 100%, while the sensitivity was 81.5% for whole blood specimens, 79% for serum specimens, and 99.2% for whole blood and serum specimens combined. The results suggest that the detection of Brucella DNA in whole blood and serum specimens by PCR-EIA assay is a sensitive and specific method that could assist the rapid and accurate diagnosis of acute human brucellosis.