[Protective effect of selenium in acute T-2 mycotoxicosis].
Male Wistar rats were fed diets supplemented with selenium (0.5 and 2.5 mg/kg) for 6 weeks. When T-2 toxin was administered at 3.8 mg/kg body weight; sings of intoxication were less distinct in rats fed selenium-supplemented diets. Mortality caused by T-2 toxin was two times lower if selenium content amounted to 2.5 mg/kg. The level of cytochrome P-450 and the rate of deethylation of 7-ethoxycoumarin were considerably decreased in the liver of rats that received T-2 toxin and fed a diet with high selenium content. At the same time the activity of epoxide hydrolase and UDP-glucuronosyltransferase was significantly higher (1.6 and 1.7 times more) as compared with unsupplemented group. The results obtained allow to assume that there is a relationship between the decrease of T-2 toxin toxicity and the change in its metabolism in rats fed selenium-supplemented diets.


[Sudden cardiac death in familial hypertrophic cardiomyopathy. Identification of high-risk patients].
Hypertrophic cardiomyopathy (HCM) is a relatively frequent, genetically determined primary cardiomyopathy, characterized by most often asymmetric hypertrophy of the ventricular septum with or without systolic obstruction of the left ventricular outflow tract. HCM is a genetically heterogeneous disease, with 12 different disease-causing genes beeing indentified to date. Histologically the disease is characterized by hypertophy and disarray of myofibrils as well as by an increase in myocardial fibrosis. Clinically, these changes may lead to palpitations, dyspnoe on exertion, and/or angina pectoris. However, they also lead to an increased propensity to the development of severe ventricular tachyarrhythmias and sudden cardiac death. The incidence of sudden death is significantly increased in HCM, particularly in affected young subjects. Risk stratification in HCM should include a complete clinical-cardiological evaluation that should also consider new diagnostic features, e. g. MR imaging. Major risk factors for sudden cardiac death include a survived cardiac arrest (ventricular fibrillation), non-sustained and sustained ventricular tachycardia, a history of premature familial sudden death, unexplained syncope, an abnormal blood pressure response on exercise, and left ventricular thickness greater than or equal to 3 cm. Ideally, risk stratification should also include genetic testing, since some gene mutations seem to be associated with a higher risk for sudden cardiac death than others. However, genetic testing in HCM in not yet available on a routine basis. The implantation of a cardioverter/defibrillator is first-line therapy in patients with documented ventricular tachycardia/fibrillation or patients who have survived sudden cardiac death. These devices also play an important role in the primary prevention of sudden cardiac death in HCM. Algorithms and scores are available to estimate the risk of sudden death, however, the decision to implant a cardioverter/defibrillator remains an individual decision in every single patient.


MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells.
Chromosome-wide inactivation is an epigenetic signature of sex chromosomes. The mechanism by which the chromosome-wide domain is recognized and gene silencing is induced remains unclear. Here we identify an essential mechanism underlying the recognition of the chromosome-wide domain in the male germline. We show that mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX), defines the chromosome-wide domain, initiates meiotic sex chromosome inactivation (MSCI), and leads to XY body formation. Importantly, MSCI consists of two genetically separable steps. The first step is the MDC1-independent recognition of the unsynapsed axis by DNA damage response (DDR) factors such as ataxia telangiectasia and Rad3-related (ATR), TOPBP1, and γH2AX. The second step is the MDC1-dependent chromosome-wide spreading of DDR factors to the entire chromatin. Furthermore, we demonstrate that, in somatic cells, MDC1-dependent amplification of the γH2AX signal occurs following replicative stress and is associated with transcriptional silencing. We propose that a common DDR pathway underlies both MSCI and the response of somatic cells to replicative stress. These results establish that the DDR pathway centered on MDC1 triggers epigenetic silencing of sex chromosomes in germ cells.


In Vitro Skin Permeation Methodology for Over-The-Counter Topical Dermatologic Products.
For topically applied over-the-counter (OTC) products, the association of unwanted systemic exposure and adverse events may be difficult to ascertain without a recognition or determination of in vivo absorption. Evaluation of skin permeability using a validated in vitro permeation methodology can provide important information for both initial formulation selection and reformulation during the product life cycle. Additionally, a comparison of permeation rates between formulations using a validated methodology could reduce the number of nonclinical studies needed as part of reformulation. However, many in vitro permeation tests (IVPTs) have produced results with high variability and low reproducibility between study sites. It is unclear if this is due to a lack of a standardized protocol, or lack of control of multiple key experimental factors including skin source, preparation, receptor fluid, and study design. This review presents the authors perspective on the potential regulatory utility of IVPT and proposes steps to improve the accuracy and reproducibility of IVPT. The focus of this review is on topical dermatologic drugs with an initial emphasis on the OTC marketplace where reformulations are more common.


A pharmacovigilance study on antiepileptic medications in a paediatric hospital in Italy.
The standard treatment for epilepsy is based on the appropriate use of antiseizure medications (ASMs) to prevent the recurrence of seizures. For the newer ASMs, however, little information on their safety profile is available. This work sought to fill this gap by creating a database for ASM use in a paediatric hospital and the adverse drug reactions (ADRs) reported. This observational single-centre study was conducted from January 2018 to December 2020 and recorded the type of ASM treatment for paediatric epileptic patients cared for at the Neuropsychiatry Unit of the Salesi Paediatric Hospital in Ancona, Italy, as well as any ADRs. In all, 519 patients were admitted to the ward with a diagnosis of epilepsy, 362 (69.7%) of whom were prescribed ASMs. Valproic acid was the most frequently prescribed drug (29.96%), followed by levetiracetam (13.97%) and carbamazepine (9.16%). We recorded 24 ADRs in 20 patients, half of which (n=12) occurred with polytherapy. Among the ADRs associated with monotherapy, 25% (n=6) were induced by carbamazepine; 12.5% (n=3) were associated with either valproic acid, clonazepam or lamotrigine; 8.3% (n=2) were associated with perampanel, clobazam or levetiracetam; while one patient experienced ADR due to vigabatrin, one due to ethosuximide and one due to cannabidiol. The median patient age was 7.5 years and most ADRs were not serious. During the 3-year observation period, 6% of epileptic patients on ASMs showed one or more ADRs. Carbamazepine was responsible for about a quarter of these reactions, two of which were serious. Half of the ADRs occurred with polytherapy, which often included valproic acid and stiripentol. It is to be hoped that such active pharmacovigilance through the collaboration of hospital pharmacists and physicians will serve to improve the management of treatment.


Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.
SS-cream is a topical agent made from the extracts of natural products for treating premature ejaculation (PE). To determine the optimal clinical dosage of SS-cream on PE, we investigated the safety and efficacy of SS-cream with various doses. A double blind, randomized placebo controlled clinical study was performed. Fifty patients completed the study. Mean age of the patients was 37.1+/-1.O y and mean ejaculatory latency was 1.35+/-0.07 min. Sexual satisfaction rate of both the partner and patient was 16.2%. Each patient was instructed to apply the different cream (placebo, SS-cream 0.05, 0.10, 0.15, 0.20 g) on glans penis 1 h before sexual intercourse in random fashion. The ejaculatory latency was measured by stop watch and the satisfaction rate of both partner and patient was also recorded two times in the screening period and after the application of each test drugs. Clinical efficacy was considered if ejaculatory latency was prolonged more than 2 min and sexual satisfaction rate increased more than 20% than that of pretest values. The mean ejaculatory latencies were significantly prolonged after using various test drugs (placebo 2.27+/-0.32, SS-cream 0.05 g 4.47+/-0.81, 0.10 g 5.34+/-0.79, 0.15 g 6.22+/-0.87, 0.20 g 11.06+/-1.17 min, respectively). Clinical efficacies evaluated by ejaculatory latency were placebo 18%, SS-cream 0.05 g 30%, 0.10 g 60%, 0.15 g 54%, 0.20 g 84%, respectively. The satisfaction rate was also significantly increased dose-dependently (placebo 26%, SS-cream 0.05 g 60%, 0.10 g 70%, 0.15 g 78%, 0.20 g 90%, respectively). A side effect such as local mild burning sensation was noted in 35/250 times (14%) and no adverse effect on sexual function and no systemic side effects were observed. From the result of logistic regression analysis on clinical efficacy, the ED50 of SS-cream was obtained as 0.10 g. SS-cream 0.20 g was effective in 84% without any serious systemic side effects. From the above results, our conclusions are that SS-cream is effective on the treatment of PE with a few local side effects and that clinical optimal dose of SS-cream is 0.20 g.


Quality improvement interventions to prevent healthcare-associated infections in neonates and children.
Healthcare-associated infections cause substantial harm to hospitalized neonates and children. Efforts that prevent these infections are a major focus of current patient safety initiatives. This review focuses on the reports of quality improvement interventions to prevent central line-associated bloodstream infections (CLABSIs) in neonates and children. Single-center and multicenter collaborative studies have examined the effect of quality improvement interventions to reliably implement central line insertion and maintenance bundles on CLABSI rates in neonatal and pediatric intensive care units. Quality improvement interventions were associated with reductions in CLABSI rates in neonates and children by a half or more, although many of the studies have important methodologic limitations. Studies that utilized improvement science methodologies demonstrated larger improvement effects, but required a sizable investment of institutional support and personnel time. Quality improvement interventions to reduce CLABSI are an important component of patient safety initiatives. Future studies of quality improvement interventions to reduce HAI among hospitalized neonates and children will benefit from further investigation of methods to enhance reliable implementation of evidence-based practices, factors that enable multicenter collaboratives to be more successful, and better understanding of the causes of heterogeneity in the results at different centers.


Australian Trends in Academic Literature Concerned With Family and Domestic Violence Perpetrators: A Bibliometric Literature Review.
In this article, we used a novel hybrid approach to review literature concerned with family and domestic violence (FADV) perpetrators. Our intention was to chart the research and publication activity of authors with Australian affiliation to identify homegrown evidence related to stopping the perpetration of violence. This involved systematic searching of literature from the Scopus electronic database, utilization of VOSviewer to sort keyword co-occurrences and authorship linking for 1,494 publication records over a 30-year period, and the review of 21 articles with perpetrator focus, identified from the 50 most cited publications. We found that Australians' authoring interests in FADV, over the last three decades, with perpetrator focus were predominantly concentrated on gender, rape and sexual assault, coercive control, and child abuse. In the most cited literature, six major themes were identified: perpetrator motivations, perpetrator interventions, patterns of violence, pandemic duet, perception of blame, and cyberstalking and violence. An upward curve in Australian authoring activity in the period under review aligns with societal shifts in which FADV was once considered a private issue and has now become ubiquitous in the public domain. Our findings revealed that research into perpetrators is insufficient to promote a zero-tolerance approach to FADV. Our corresponding in-depth literature review provides valuable insights surrounding perpetrator intervention programs with the goal of more effectively addressing the emerging challenge of technology-facilitated coercive control.


Spatiotemporal control over growth factor delivery from collagen-based membrane.
Exogenous administration of growth factors has been identified as a potential therapeutic approach for healing wounds. A way to enhance the efficacy of growth factors would be to achieve spatiotemporal control over their delivery to desired sites for an extended period. In this study, we designed and prepared a kind of double-layered collagen membrane, a dense layer and a loose layer, which incorporated basic fibroblast growth factor (bFGF)-loaded chitosan-heparin nanoparticles. The nanoparticles were prepared by polyelectrolyte gelation process and then were sandwiched between the two layers of collagen membrane. The release of model protein human serum albumin (HSA) from the double-layered membrane was tracked by radio-label assay, and the bioactivity of the growth factor on fibroblast cell (L929) was evaluated by MTT assay. The release of protein displayed a spatiotemporal control model and its release in undesired direction was lessened. The bFGF maintained the bioactivities after release from the membranes. Moreover, different release amounts of bFGF from the different layers of the membrane induced significant difference in cell proliferation when the cells were seeded on the different layers of membrane in vitro. This kind of double-layered collagen membrane could have potential applications in the field of tissue repair due to the spatiotemporal control over growth factor delivery, the mild fabrication conditions, and the simple processes.


The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study.
Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut-joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (n = 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies.


Sensitivity Improvement to Active Piezoresistive AFM Probes Using Focused Ion Beam Processing.
This paper presents a comprehensive modeling and experimental verification of active piezoresistive atomic force microscopy (AFM) cantilevers, which are the technology enabling high-resolution and high-speed surface measurements. The mechanical structure of the cantilevers integrating Wheatstone piezoresistive was modified with the use of focused ion beam (FIB) technology in order to increase the deflection sensitivity with minimal influence on structure stiffness and its resonance frequency. The FIB procedure was conducted based on the finite element modeling (FEM) methods. In order to monitor the increase in deflection sensitivity, the active piezoresistive cantilever was deflected using an actuator integrated within, which ensures reliable and precise assessment of the sensor properties. The proposed procedure led to a 2.5 increase in the deflection sensitivity, which was compared with the results of the calibration routine and analytical calculations.


Dose-Dependent Synergistic Interactions of Colistin with Rifampin, Meropenem, and Tigecycline against Carbapenem-Resistant Klebsiella pneumoniae Biofilms.
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) can cause biofilm-related bloodstream infections associated with significant morbidity and mortality worldwide. We investigated the bactericidal activities of colistin (CST), rifampin (RIF), meropenem (MEM), gentamicin (GEN), and tigecycline (TGC) alone and that of CST in combination with RIF, MEM, GEN, or TGC against CR-Kp mature biofilms. Twenty CR-Kp blood isolates were derived from an equal number of bloodstream infections in adult patients. Biofilm formation was assessed by staining with 0.4% crystal violet and measuring the optical density spectrophotometrically at 545 nm. Biofilm damage was measured as the percent reduction of metabolic activity by an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] assay. The MIC50 for biofilms was determined as the minimum concentration that caused ≥50% bacterial damage compared to that for untreated controls. Antibacterial drug interactions were analyzed by the Bliss independence model. Four of the 20 CR-Kp isolates were biofilm producers. Biofilm MIC50s of CST, RIF, MEM, GEN, and TGC for these isolates were 64, 8, >256, 128, and 8 mg/liter, respectively. Synergistic interactions were observed at 32 to 64 mg/liter of CST combined with 0.25 to 4 mg/liter of RIF, at 32 mg/liter of CST combined with 0.007 to 0.25 mg/liter of MEM, and at 16 to 32 mg/liter of CST combined with 16 to 64 mg/liter of TGC. The synergy was highest for CST plus RIF, with a mean ΔE ± standard error (SE) of 49.87% ± 9.22%, compared to 29.52% ± 4.97% for CST plus MEM (P < 0.001) and 32.44% ± 6.49% for CST plus TGC (P < 0.001). Indifferent results were exhibited by CST plus GEN. None of the combinations exhibited antagonism. These drug interaction findings, especially those for CST with RIF, may be of importance in the treatment of biofilm-related CR-Kp infections.


Day-to-Day Blood Pressure Variability and Risk of Incident Chronic Kidney Disease in a General Japanese Population.
Background Several longitudinal studies have reported that higher visit-to-visit blood pressure variability is associated with greater risk for developing chronic kidney disease. However, no population-based studies have investigated the association between day-to-day home blood pressure variability and incident chronic kidney disease. Methods and Results A total of 2342 Japanese community-dwelling residents aged ≥40 years without chronic kidney disease at baseline were followed up by annual health examinations for 10 years. Home blood pressure was measured 3 times every morning for 28 days. Day-to-day coefficients of variation of home systolic blood pressure levels were categorized into quintiles. Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m2 or the presence of proteinuria. The hazard ratios for developing chronic kidney disease were estimated with a Cox proportional hazards model. During the follow-up period, 772 participants developed chronic kidney disease. Increased coefficients of variation of home systolic blood pressure were associated significantly with higher risk of chronic kidney disease after adjusting for confounders (P for trend <0.001): Individuals in the highest quintile of coefficients of variation had a 1.50-fold (95% CI, 1.17-1.94) greater risk of developing chronic kidney disease than those in the lowest quintile. The combination of higher coefficients of variation and higher mean value of home systolic blood pressure was associated with the multivariable-adjusted risk of developing chronic kidney disease. Conclusions These findings suggest that increased day-to-day blood pressure variability is a significant risk factor for developing chronic kidney disease in a general Japanese population.


[Meningocerebral hernia and defects of the tegmen. Diagnosis and surgical treatment].
Eight defects of the tegmen tympani or antri have been operated on during the last two years. Among these cases, 4 brain herniae were associated with the defect of the tegmen. Magnetic resonance imaging permitted to evaluate accurately the space occupying lesions into the mastoid cavity and disclosed the brain and/or meningeal herniations. The defect of the tegmen was oblitered through a middle fossa approach whereas the hernia was resected through a mastoid approach when necessary.


Analysis of Cadmium Contamination in Lettuce (Lactuca sativa L.) Using Visible-Near Infrared Reflectance Spectroscopy.
In order to rapidly and accurately monitor cadmium contamination in lettuce and understand the growth conditions of lettuce under cadmium pollution, lettuce is used as the test material. Under different concentrations of cadmium stress and at different growth stages, relative chlorophyll content of lettuce leaves, the cadmium content in the leaves, and the visible-near infrared reflectance spectra are detected and analyzed. An inversion model of the cadmium content and relative chlorophyll content in the lettuce leaves is established. The results indicate that cadmium concentrations of 1 mg/kg and 5 mg/kg promote relative chlorophyll content, while concentrations of 10 mg/kg and 20 mg/kg inhibit relative chlorophyll content. The cadmium content in the leaves increases with increasing cadmium concentrations. Cadmium stress caused a "blue shift" in the red edge position only during the mature period, while the red valley position underwent a "blue shift" during the seedling and growth periods and a "red shift" during the mature period. The green peak position exhibited a "blue shift". After model validation, it was found that the model constructed using the ratio of red edge area to yellow edge area and the normalized values of red edge area and yellow edge area effectively estimated the cadmium content in lettuce leaves. The model established using the normalized vegetation index of the red edge and the ratio of the peak green value to red shoulder amplitude can effectively estimate the relative chlorophyll content in lettuce leaves. This study demonstrates that the visible-near infrared spectroscopy technique holds great potential for monitoring cadmium contamination and estimating chlorophyll content in lettuce.


Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention.
The duration of time that elective noncardiac surgery (NCS) should be delayed after percutaneous coronary intervention (PCI) with bare metal stents (BMSs) is unknown. This large, single-center, retrospective study examined the relation between complication rate in patients with BMSs undergoing NCS and the duration of time between PCI and NCS. Primary endpoints included in-hospital major adverse cardiac events (death, myocardial infarction, stent thrombosis, or repeat revascularization with either coronary artery bypass grafting or PCI of the target vessel) and bleeding events. The relation between the events and the timing of noncardiac surgery after PCI with BMS was assessed using univariate analysis and multiple logistic regression. From January 1, 1990, to January 1, 2005, a total of 899 patients were identified. The frequency of major adverse cardiac events was 10.5% when NCS was performed less than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90 days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after PCI with BMS. In univariate and multivariate analyses, a shorter time interval between PCI with BMS and noncardiac surgery was significantly associated with increased incidence of major adverse cardiac events (univariate: P < 0.001; odds ratio = 4.0; 95% confidence interval, 2.0-8.3; multivariate: P = 0.006; odds ratio = 3.2; 95% confidence interval, 1.5-6.9). Bleeding events were not associated with time between PCI with BMS and NCS or with the use of antiplatelet therapy in the week before NCS. The incidence of major adverse cardiac events is lowest when NCS is performed at least 90 days after PCI with BMS.


Association between bacterial vaginosis and partner concurrency: a longitudinal study.
The study aimed to test if there was an association between prevalent bacterial vaginosis (BV) and women reporting that their partner had other partners at the same time (partner concurrency). This association has not been assessed in a longitudinal cohort. The Longitudinal Study of Vaginal Flora recruited a cohort of 3620 non-pregnant women aged 15-44 years who presented for routine primary healthcare at 12 clinics in Birmingham, Alabama. Behavioural questionnaires and vaginal smears were obtained quarterly for a year and BV was defined by a Nugent score 7 or higher as well as Amsel criteria. Mixed effects logistic regression was used to assess the relationship between prevalent BV and reporting that one's partner had other partners in the preceding 3-6 months time interval. Nugent score prevalent BV was associated with both reporting that one's partner definitely (adjusted OR (aOR) 1.5; 95% CI 1.2 to 1.8) and possibly (aOR 1.5; 95% CI 1.2 to 1.8) engaged in partner concurrency in the preceding 3-6 months time period. Prevalent BV diagnosed by Amsel criteria was similar. A diagnosis of prevalent BV was associated with reporting that one's partner possibly or definitely engaged in partner concurrency.


Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma.
Recent studies have shown that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes are associated with the pathogenesis of aldosterone-producing adenoma. Clinical profile and biochemical characteristics of the mutations in Chinese patients with aldosterone-producing adenoma remain unclear. In this study, we performed DNA sequencing in 168 Chinese patients with aldosterone-producing adenoma and found 129 somatic mutations in KCNJ5, 4 in ATP1A1, 1 in ATP2B3, and 1 in CACNA1D. KCNJ5 mutations were more prevalent in female patients and were associated with larger adenomas, higher aldosterone excretion, and lower minimal serum K(+) concentration. More interestingly, we identified a novel somatic KCNJ5 mutation (c.445-446insGAA, p.T148-T149insR) that could enhance CYP11B2 mRNA upregulation and aldosterone release. This mutation could also cause membrane depolarization and intercellular Ca(2+) increase. In conclusion, somatic KCNJ5 mutations are conspicuously more popular than mutations of other genes in aldosterone-producing adenomas of Chinese patients. The T148-T149insR mutation in KCNJ5 may influence K(+) channel selectivity and autonomous aldosterone production.


[Changes in gastric electric activity and serum catecholamine level under the influence of electromagnetic microwaves (experimental studies)].
Chronic experiments on 17 dogs revealed that ultrahigh-frequency electromagnetic waves applied on epigastric area and head induce a double-phase response: depressed electric activity of gaster and increased total catecholamines level during exposure, but higher gastric activity and lower levels of epinephrine and norepinephrine in 24 hours after each of 10 procedures and during 7 days after 10 procedures. Double-phase changes in electric activity of gaster could be explained by double-phase fluctuations of humoral division in chromaffin system.


Stratigraphic sections, bedding sequences, and random processes.
Both dependent and independent random processes can be used to study and synthesize stratigraphic sections and bedding sequences. Synthetic stratigraphic sections can be modeled to fit any geologic problem with a good correspondence between the synthetic and actual stratigraphic sections. To synthesize a sedimentary sequence, one needs only a transition procedure to go from one lithology or bedding type to another, and frequency distributions of thickness for the various lithologies. A sedimentation process with a "memory" is termed Markovian; if the past has no influence on either present or future sedimentation, it is called an independent trials process.


Sequential push-pull pumping mechanism for washing and evacuation of an immunoassay reaction chamber on a microfluidic CD platform.
A centrifugal compact disc (CD) microfluidic platform with reservoirs, micro-channels, and valves can be employed for implementing a complete immunoassay. Detection or biosensor chambers are either coated for immuno-interaction or a biosensor chip is inserted in them. On microfluidic CDs featuring such multi-step chemical/biological processes, the biosensor chamber must be repeatedly filled with fluids such as enzymes solutions, buffers, and washing solutions. After each filling step, the biosensor chamber needs to be evacuated by a passive siphoning process to prepare it for the next step in the assay. However, rotational speed dependency and limited space on a CD are two big obstacles to performing such repetitive filling and siphoning steps. In this work, a unique thermo-pneumatic (TP) Push-Pull pumping method is employed to provide a superior alternative biosensor chamber filling and evacuation technique. The proposed technique is demonstrated on two CD designs. The first design features a simple two-step microfluidic process to demonstrate the evacuation technique, while the second design shows the filling and evacuation technique with an example sequence for an actual immunoassay. In addition, the performance of the filling and evacuation technique as a washing step is also evaluated quantitatively and compared to the conventional manual bench top washing method. The two designs and the performance evaluation demonstrate that the technique is simple to implement, reliable, easy to control, and allows for repeated push-pulls and thus filling and emptying of the biosensor chamber. Furthermore, by addressing the issue of rotational speed dependency and limited space concerns in implementing repetitive filling and evacuation steps, this newly introduced technique increases the flexibility of the microfluidic CD platform to perform multi-step biological and chemical processes.


Speciation analysis of organoarsenic species in marine samples: method optimization using fractional factorial design and method validation.
Organoarsenic species in marine matrices have been studied for many years but knowledge gaps still exist. Most literature focuses on monitoring of arsenic (As) species using previously published methods based on anion- and cation-exchange high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). These studies are often limited to few As species and/or only specific method performance characteristics are described. Most marine certified reference materials (CRMs) are only certified for arsenobetaine (AB) and dimethylarsinate (DMA), making it difficult to evaluate the accuracy of analytical methods for other organoarsenic species. To address these gaps, the main objective of this work was to develop and validate a method for speciation analysis of a broad range of organoarsenic species in marine matrices. Optimum extraction conditions were identified through a 27-3 fractional factorial design using blue mussel as test sample. The effects of sample weight, type and volume of extraction solution, addition of H2O2 to the extraction solution, extraction time and temperature, and use of ultrasonication were investigated. The highest As recoveries were obtained by using 0.2 g as sample weight, 5 mL of aqueous methanol (MeOH:H2O, 50% v/v) as extractant, extraction carried out at 90 °C for 30 min, and without ultrasonication. Anion- and cation-exchange HPLC-ICP-MS settings were subsequently optimized. The method detected a total of 33 known and unknown As species within a run time of 23 and 20 min for cation-exchange and anion-exchange, respectively. A single-laboratory validation was conducted using several marine CRMs: BCR 627 (tuna fish tissue), ERM-CE278k (mussel tissue), DORM-4 (fish protein), DOLT-5 (dogfish liver), SQID-1 (cuttlefish), TORT-3 (lobster hepatopancreas), and CRM 7405-b (hijiki seaweed). Method performance characteristics were evaluated based on selectivity, limits of detection and quantification, linearity, trueness, precision, and measurement uncertainty. This work proposes an extraction procedure which allowed satisfactory quantification of As species with low solvent and energy consumption, supporting "Green Chemistry" principles. The study also presents a new set of As speciation data, including methylated arsenic species and arsenosugars, in recently issued marine CRMs, which will be valuable for future speciation studies on As. This work is the first to report a total of 33 different As species in marine CRMs.


The changing role of quality assurance: an international industry perspective.
As a Scientific Consultant in the area of Good Laboratory Practice and Good Clinical Practice the author has been involved with Quality Assurance (QA) for 18 years and fells the time has come for Industry to explore a better way to utilize the many talents that the QA professional has achieved. They have a wealth of expertise and should become more involved in the integration of "science" with the many "GXPs" to ensure that compliance is arrived at on a cost benefit basis for the company.


Likelihood of additional work-up among women undergoing routine screening mammography: the impact of age, breast density, and hormone therapy use.
Mammography screening can involve subsequent work-up to determine a final screening outcome. Understanding the likelihood of different events that follow initial screening is important if women and their health care providers are to be accurately informed about the screening process. We conducted an analysis of additional work-up following screening mammography to characterize use of supplemental imaging and recommendations for biopsy and/or surgical consultation and the factors associated with their use. We included all events following screening mammography performed between 1/1/1998 and 12/31/1999 on a population-based sample of 37,632 New Hampshire women. We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) for supplemental imaging and recommended biopsy and/or surgical consultation as function of age, menopausal status and HRT use, breast density, and family history of breast cancer. Ninety-one percent of women (n = 34,445) did not require supplemental imaging. Among those who did (n = 3187), 84% had additional views, 9% ultrasound, and 7% received both. Supplemental imaging was affected by age (OR 0.84; 95% CI = 0.76-0.94 for 50-59; OR = 0.66; 95% CI = 0.58-0.75 for > or = 60 versus < 50), menopausal status, and HRT use (OR = 1.33; 95% CI = 1.21-1.47 for peri- or post-menopausal HRT users; OR = 1.14; 95% CI = 1.01-1.29 for premenopausal versus peri- or post-menopausal non-HRT users), breast density (OR = 1.43; 95% CI = 1.33-1.55 for dense versus fatty breasts) and family history (OR = 1.15; 95% CI = 1.06-1.25 for any versus none). In women with supplemental imaging, age (OR = 1.80; 95% CI = 1.11-2.90 for > or = 60, relative to <50) and imaging type (OR = 3.23; 95% CI = 2.38-4.38 for ultrasound with or without additional views versus additional views only) were significantly associated with biopsy and/or surgical consultation recommendation. In those with no supplemental imaging, breast density was associated with recommended biopsy and/or surgical consultation (OR = 1.53; 95% CI = 1.13-2.07 for dense versus fatty breasts). Breast density and HRT use are both independent predictors of use of supplemental imaging in women. With advancing age (age 60 and older), women were less likely to require follow-up imaging but more likely to receive a recommendation for biopsy and/or surgical consultation. This information should be used to inform women about the likelihood of services received as part of the screening work-up.


Hysterectomy in obstetric practice.
A 9-year review (1971-1979) is presented of patients undergoing hysterectomy in the course of pregnancy. The incidence was 1 in 1,044 pregnancies (34 in 35,506). The principal indications were ruptured uterus (9), postpartum haemorrhage (8), placenta accreta (5) and neoplastic trophoblastic disease (4). In spite of the high incidence of hysterectomy in our community, the procedure was undertaken during pregnancy with great reluctance and usually only as a life-saving procedure.


Continued Stabilization of a Cementless 3D-Printed Total Knee Arthroplasty: Five-Year Results of a Randomized Controlled Trial Using Radiostereometric Analysis.
Three-dimensional (3D) printing of highly porous orthopaedic implants aims to promote better osseointegration, thus preventing aseptic loosening. However, short-term radiostereometric analysis (RSA) after total knee arthroplasty (TKA) has shown higher initial migration of cementless 3D-printed tibial components compared with their cemented counterparts. Therefore, critical evaluation of longer-term tibial component migration is needed. We investigated migration of a cementless 3D-printed and a cemented tibial component with otherwise similar TKA design during 5 years of follow-up, particularly the progression in migration beyond 2 years postoperatively. Seventy-two patients were randomized to a cementless 3D-printed Triathlon Tritanium (Stryker) cruciate-retaining (CR) TKA or a cemented Triathlon CR (Stryker) TKA implant. Implant migration was evaluated with RSA at baseline and postoperatively at 3 months and at 1, 2, and 5 years. The maximum total point motion (MTPM) of the tibial component was compared between the groups at 5 years, and progression in migration was assessed between 2 and 5 years. Individual implants were classified as continuously migrating if the MTPM was ≥0.1 mm/year beyond 2 years postoperatively. Clinical scores were evaluated, and a linear mixed-effects model was used to analyze repeated measurements. At 5 years, the mean MTPM was 0.66 mm (95% confidence interval [CI], 0.56 to 0.78 mm) for the cementless group and 0.53 mm (95% CI, 0.43 to 0.64 mm) for the cemented group (p = 0.09). Between 2 and 5 years, there was no progression in mean MTPM for the cementless group (0.02 mm; 95% CI, -0.06 to 0.10 mm) versus 0.07 mm (95% CI, 0.00 to 0.14) for the cemented group. One implant was continuously migrating in the cementless group, and 4 were continuously migrating in the cemented group. The clinical scores were comparable between the groups across the entire time of follow-up. No significant difference in mean migration was found at 5 years between the cementless and cemented TKA implants. Progression of tibial component migration was present beyond 2 years for the cemented implant, whereas the cementless implant remained stable after initial early migration. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.


Exercise Therapy and Cardiovascular Toxicity in Cancer.
Cardio-oncology is an emerging discipline focused predominantly on the detection and management of cancer treatment-induced cardiac dysfunction (cardiotoxicity), which predisposes to development of overt heart failure or coronary artery disease. The direct adverse consequences, as well as those secondary to anticancer therapeutics, extend beyond the heart, however, to affect the entire cardiovascular-skeletal muscle axis (ie, whole-organism cardiovascular toxicity). The global nature of impairment creates a strong rationale for treatment strategies that augment or preserve global cardiovascular reserve capacity. In noncancer clinical populations, exercise training is an established therapy to improve cardiovascular reserve capacity, leading to concomitant reductions in cardiovascular morbidity and its attendant symptoms. Here, we overview the tolerability and efficacy of exercise on cardiovascular toxicity in adult patients with cancer. We also propose a conceptual research framework to facilitate personalized risk assessment and the development of targeted exercise prescriptions to optimally prevent or manage cardiovascular toxicity after a cancer diagnosis.


Meat morals: relationship between meat consumption consumer attitudes towards human and animal welfare and moral behavior.
The aim of this work is to explore the relation between morality and diet choice by investigating how animal and human welfare attitudes and donation behaviors can predict a meat eating versus flexitarian versus vegetarian diet. The results of a survey study (N=299) show that animal health concerns (measured by the Animal Attitude Scale) can predict diet choice. Vegetarians are most concerned, while full-time meat eaters are least concerned, and the contrast between flexitarians and vegetarians is greater than the contrast between flexitarians and full-time meat eaters. With regards to human welfare (measured by the Moral Foundations Questionnaire), results show that attitudes towards human suffering set flexitarians apart from vegetarians and attitudes towards authority and respect distinguish between flexitarians and meat eaters. To conclude, results show that vegetarians donate more often to animal oriented charities than flexitarians and meat eaters, while no differences between the three diet groups occur for donations to human oriented charities.


Evaluation of working capacity in case of mental disorders.
Incidence of mental disorders in our country and in the world is growing and significantly impact working capacity. The goal of the study: to investigate which group of mental disorders and to what extent impacts the disability comparing two analyzed years (1999 and 2009). 420 subjects were processed (143 in 1999 and 277 in 2009) from the Una-Sana Canton with mental disorders who were referred for evaluation of working capacity at professional authority in the first instance (Disability Commission) in Bihac. Disability Commission gave "Review, assessment and opinion" for each individual from which the author recorded data into the questionnaire necessary for the study. More men are sent for evaluation, aged 50 and over, who are not employed. Number of assessments has increased by almost double. The most addressed are from the group of affective disorders, who did not have disability during 1999 in majority, but in 2009 they are the leaders in disability, with schizophrenia. There is increased number of assessments, and most of them from the group of affective disorders whose participation in disability increases. Schizophrenia and affective disorders are the leading causes of disability.


Update on Endoscopic Approaches for the Management of Gastroesophageal Reflux Disease.
Gastroesophageal reflux disease (GERD) is one of the most commonly encountered gastrointestinal diseases in outpatient clinics. Proton pump inhibitors (PPIs) are the cornerstone of the treatment of GERD. However, approximately one-third of patients have suboptimal response to PPIs. The management options in such cases include antireflux surgery or endoscopic antireflux treatments. Antireflux surgery is not popular due to its invasive nature and potential for adverse events. Therefore, minimally invasive endoscopic antireflux therapies are gaining popularity for the management of PPI-dependent and PPI-refractory GERD. These endoscopic therapies include radiofrequency application, endoscopic fundoplication modalities, and mucosal resection techniques. In appropriately selected patients, the response to these endoscopic modalities is encouraging. Unlike surgical fundoplication, endoscopic antireflux therapies are less likely to be associated with complications such as dysphagia and gas-bloat syndrome. On the other hand, antireflux surgery remains the ideal treatment in patients with a large hiatal hernia (laparoscopic Nissen fundoplication), morbid obesity (gastric bypass), and severe reflux esophagitis. Endoscopic treatment modalities bear the potential to narrow the treatment gap between PPIs and antireflux surgery. Long-term follow-up studies and randomized comparison with antireflux surgery are required to provide a clear understanding of the current role of endoscopic modalities in patients with PPI-refractory and PPI-dependent GERD.


Vaginal hysterectomy be anterior delivery of the uterine corpus.
Of 285 vaginal hysterectomies done by a modification of the Doderlein-Kronig technic, almost 70% of patients had an intraoperative blood loss of less than 200 ml. Only four required transfusions. A postoperative pelvic abscess was the only severe infection, and it responded to treatment. One patient had a ruptured ectopic pregnancy 46 days after hysterectomy. Advantages of this procedure are good anatomic exposure and minimal blood loss.


Signs, symptoms, and ill-defined conditions in Persian Gulf War veterans: findings from the Comprehensive Clinical Evaluation Program.
The purpose of this study was to analyze the type and frequency of signs, symptoms, and ill-defined conditions (SSID; International Classification of Diseases-9th Revision, Clinical Modification (ICD-9-CM) codes 780-799) identified by physicians evaluating Persian Gulf War veterans; to determine the influence of the extent of evaluation on the type and frequency of SSID diagnoses; and to search for evidence for a new illness, or illness related to wartime exposures, in veterans with ill-defined conditions. Comprehensive examinations were provided for 21,579 consecutive Persian Gulf War veterans with symptoms or health concerns after the war. Data recorded on all individuals includes demographics, self-reported exposures, symptoms, and physician-assigned ICD-9-CM primary and secondary diagnoses. A detailed psychosocial history, including a multidisciplinary discussion, was incorporated for a subset of participants. SSID conditions were primary diagnoses for 17.2% of veterans, and either primary or secondary diagnoses for 41.8%. Although some SSIDs were objective conditions (eg, sleep apnea), most were simply symptoms. More comprehensive evaluation, especially the multidisciplinary discussion of findings, decreased the frequency of symptoms as diagnoses and increased the number of DSM-IV psychiatric diagnoses. Ill-defined conditions were not associated with particular self-reported exposures or demographic variables. Ill-defined conditions identified by physicians in Gulf War veterans are most often symptoms. More definitive, often psychological, diagnoses can be made by increasing the intensity of the evaluation and by multidisciplinary input. Evidence for a new or unique illness related to wartime exposures did not emerge from this analysis.


Presurgical Orthopedic Intervention Prior to Cleft Lip and Palate Repair: Nasoalveolar Molding Versus Passive Molding Appliance Therapy.
Nasoalveolar molding (NAM) is a widely used presurgical orthopedic device, despite disputes over its effectiveness. This study compares the outcomes after cleft lip and nose repair in patients who received NAM versus those who underwent passive alveolar molding with lip taping. A retrospective review of patients with complete unilateral cleft lip and palate who received either NAM (n = 16) or passive molding (n = 10) treatments was conducted. Alveolar gap width was measured on maxillary casts until time of palatoplasty. Nasolabial symmetry was assessed by examining anthropometric ratios on post-operative three-dimensional photographs. Burden of care was evaluated by analyzing the number of patient appointments attended, treatment costs, and caregiver satisfaction surveys. No statistically significant difference existed in alveolar gap at time of initial appointment or palatoplasty, however the gap was smaller in the NAM cohort at time of lip and nose repair. No statistically significant difference existed in postsurgical heminasal width, nostril width, nostril height, labial height or nasal ala projection asymmetry between the NAM and the passive molding cohort. Patients in the NAM group attended more dental appointments and incurred higher treatment costs compared to the passive molding group. Caregivers reported high satisfaction with treatment outcomes in both cohorts. There were no differences between NAM and passive molding regarding postsurgical nasolabial appearance and patient satisfaction. Both treatments narrow the alveolar gap. However, NAM places a higher burden of care on families.


Purification and characterization of a cytochrome P450 from liver microsomes of Xenopus laevis.
A new cytochrome P450 (P450) has been purified to near homogeneity from Xenopus laevis liver microsomes. Two steps of column chromatographies (n-octylamino Sepharose 4B and Mono Q) and fast protein liquid chromatofocusing were performed consecutively, and the final preparation containing 19 nmol P450/mg protein gave a single band of 52 kDa on SDS-PAGE at an isoelectric point of 6.7. This enzyme had a common feature of microsomal P450s in NH2-terminal region, and some of the internal sequences were similar to the corresponding sequences of reported P450s. The purified Xenopus P450 cross-reacted with antibodies against CYP2B1, rat CYP2E1, and CYP2C13, but not with rat CYP1A1, CYP3A2, or CYP4A1. Upon reconstitution with rat NADPH-cytochrome P450 reductase and phospholipid, the Xenopus P450 catalyzed aniline hydroxylation and N-nitrosodimethylamine N-demethylation. Cytochrome b5 enhanced these reactions. This P450 did not catalyze the hydroxylation of either hexobarbital or testosterone. Thus, the catalytic activities of this P450 were comparable with those of mammalian CYP2E1. Expression of this P450 was observed in liver, kidney, lung, and testis, and the level was highest in kidney. Tissue specificity of expression was the same in both male and female frogs.


Evaluating the Effects of Different Sleep Supplement Modes in Attenuating Metabolic Consequences of Night Shift Work Using Rat Model.
To study the effects of chronic-simulated night shift work using the rat model and examines if a particular sleep supplement mode could be better in alleviating the effects. The male Wistar rats were randomly divided into the control (CTL: 8 rats) and night shift work (NW: 24 rats) groups of rats. Based on the sleep supplement strategy, the NW group was further segregated into three subgroups (8 rats each); late sleep supplement group (LSS), early sleep supplement group (ESS), and intermittent sleep supplement group (ISS). Sleep deprivation was achieved using the standard small-platform-over water method. Parameters such as animal body weight and food intake were measured daily. The intraperitoneal glucose tolerance test, fasting plasma insulin concentration, insulin resistance index and insulin sensitivity were measured twice, in the 4th and 8th weeks of the study. Plasma corticosterone concentration and pathological changes in islets (insulitis) were measured at the end of the 8th week. In NW group, night work resulted in a gain of body weight and albeit lower than that of the CTL group. NW rats also had higher food intake, showed impaired glucose metabolism and higher plasma corticosterone concentration. The sleep supplement experiments suggested that compared to the other modes, intermittent sleep supplement had significantly low changes in the body weight, glucose metabolism and the islet cells. Similar to previous studies, we also found that night shift work adversely impacts the body weight and glucose metabolism in rats. However, upon evaluating different sleep supplement strategies, we found the intermittent sleep supplement strategy to be most effective.


Multiple cues for winged morph production in an aphid metacommunity.
Environmental factors can lead individuals down different developmental pathways giving rise to distinct phenotypes (phenotypic plasticity). The production of winged or unwinged morphs in aphids is an example of two alternative developmental pathways. Dispersal is paramount in aphids that often have a metapopulation structure, where local subpopulations frequently go extinct, such as the specialized aphids on tansy (Tanacetum vulgare). We conducted various experiments to further understand the cues involved in the production of winged dispersal morphs by the two dominant species of the tansy aphid metacommunity, Metopeurum fuscoviride and Macrosiphoniella tanacetaria. We found that the ant-tended M. fuscoviride produced winged individuals predominantly at the beginning of the season while the untended M. tanacetaria produced winged individuals throughout the season. Winged mothers of both species produced winged offspring, although in both species winged offspring were mainly produced by unwinged females. Crowding and the presence of predators, effects already known to influence wing production in other aphid species, increased the percentage of winged offspring in M. tanacetaria, but not in M. fuscoviride. We find there are also other factors (i.e. temporal effects) inducing the production of winged offspring for natural aphid populations. Our results show that the responses of each aphid species are due to multiple wing induction cues.


The birth and development of the forced expiratory manoeuvre: a tribute to Robert Tiffeneau (1910-1961).
The forced expiratory manoeuvre was first described by Tiffeneau and Pinelli working in Paris (France), in December 1947, who proposed measurement of the "pulmonary capacity usable on exercise" (capacité pulmonaire utilisable à l'effort) (CPUE), the maximal volume expelled in one second after a deep inspiration. It was intended to replace the measurement of the maximum breathing capacity, a difficult and tiring manoeuvre. A similar approach was later followed in the USA by Gaensler, who proposed the "timed vital capacity" in 1951. The name CPUE was changed to "volume expiratoire maximum seconde" (VEMS) by a group of European experts, who met in Paris on February 13, 1954, whereas the expression "forced expiratory volume" was adopted by the British Thoracic Society in 1957. Despite numerous attempts to examine the forced expiration in a different manner, the VEMS and/or forced expiratory volume in one second (FEV1) remain, after 50 yrs the main variables used daily by the respiratory physician. Although primarily a pharmacologist, Robert Tiffeneau (1910-1961) undoubtedly deserves to figure among the pioneers of respiratory medicine.


How to spot the recurring lumbar disc? Risk factors for recurrent lumbar disc herniation (rLDH) in adult patients with lumbar disc prolapse: a systematic review and meta-analysis.
Despite a fast-growing evidence-base examining the relationship of certain clinical and radiological factors such as smoking, BMI and herniation-type with rLDH, there remains much debate around which factors are clinically important. We conducted a systematic review and meta-analysis to identify risk factors for recurrent lumbar disc herniation (rLDH) in adults after primary discectomy. A systematic literature search was carried out using Ovid-Medline, EMBASE, Cochrane library and Web of Science databases from inception to 23rd June-2022. Observational studies of adult patients with radiologically-confirmed rLDH after ≥3 months of the initial surgery were included, and their quality assessed using the Quality-In-Prognostic-Studies (QUIPS) appraisal tool. Meta-analyses of univariate and multivariate data and a sensitivity-analysis for rLDH post-microdiscectomy were performed. Twelve studies (n=4497, mean age:47.3; 34.5% female) were included, and 11 studies (n=4235) meta-analysed. The mean follow-up was 38.4 months. Mean recurrence rate was 13.1% and mean time-to-recurrence was 24.1 months (range: 6-90 months). Clinically, older age (OR:1.04, 95%CI:1.00-1.08, n=1014), diabetes mellitus (OR:3.82, 95%CI:1.58-9.26, n=2330) and smoking (OR:1.80, 95%CI:1.03- 3.14, n=3425) increased likelihood of recurrence. Radiologically, Modic-change type-2 (OR:7.93, 95%CI:5.70-11.05, n=1706) and disc extrusion (OR:12.23, 95%CI:8.60-17.38, n=1706) increased likelihood of recurrence. The evidence did not support an association between rLDH and sex; BMI; occupational labour/driving; alcohol-consumption; Pfirmann- grade, or herniation-level. Older patients, smokers, patients with diabetes, those with type-2 Modic-changes or disc extrusion are more likely to experience rLDH. Higher quality studies with robust adjustment of confounders are required to determine the clinical bearing of all other potential risk factors for rLDH.


Spatio-temporal changes in neurofilament proteins immunoreactivity following kainate-induced cerebellar lesion in rats.
1. Spatio-temporal changes in phosphorylated (pNFP) and nonphosphorylated (npNFP) neurofilament proteins were assessed immunocytochemicaly in adult rat cerebellum, 2-30 days following unilateral injection of kainic acid (KA) or physiological saline (s.c.). 2. Analysis of the staining intensity and pattern demonstrated that injection of both KA and physiological saline elicited significant and long-lasting increase of pNFP and npNFP immunoreactivity, at the ipsilateral, and to lesser extent at the contralateral side of lesion. 3. Kainate intoxication induced abundant expression of pNFP and npNFP in cerebellar white matter, as well as in all layers of perilesioned cortex. Higher pNFP expression was evidenced in the Purkinje cell layer, particularly at cell bodies, initial segments, and proximal dendrites, which normally do not contain pNFP. In addition, synaptophysin immunocytochemistry was used as a marker of synaptogenesis and plasticity. 4. Spatio-temporal pattern of NFP and synaptophysin expression suggests that perilesioned cortex undergoes dynamic changes following brain demage and possess a reparative capacity to abridge the consequences of brain trauma.


[Diagnosis of hereditary hemochromatosis with molecular analysis of DNA in patients with anti-HCV positive liver cirrhosis. Clinical case].
A case of hereditary hemochromatosis in a patient affected by anti-HCV positive liver cirrhosis is described. The difficulties for an exact diagnosis are underlined. Really, it can be particularly difficult to make a differential diagnosis between hereditary hemochromatosis and secondary hemochromatosis, if liver cirrhosis has already been found. Practically, at this stage of disease, the histological and clinical aspects of these two forms become completely interchangeable. Moreover, diagnostic difficulties increase when, at the same time, the patient presents more causes of potential liver damage. In this case report, the DNA-analysis, obtained by polymerase chain reaction amplification and enzymatic digestion, allows to make the diagnosis of hereditary hemochromatosis, because it showed the presence of two genetic mutations, considered responsible for the disease. Both the hereditary hemochromatosis and the HCV infection, had greatly contributed to the development of liver cirrhosis. In the future, DNA-analysis by amplification with polymerase chain reaction, can assume relevant importance for the screening of affected patients' first grade parents too. It could permit an early diagnosis of hereditary hemochromatosis and then to start a timelier and more efficacious therapy, to prevent an irreversible histological damage.


Structural Phenomena in a Vesicle Membrane Obtained through an Evolution Experiment: A Study Based on MD Simulations.
The chemical evolution of biomolecules was clearly affected by the overall extreme environmental conditions found on Early Earth. Periodic temperature changes inside the Earth's crust may have played a role in the emergence and survival of functional peptides embedded in vesicular compartments. In this study, all-atom molecular dynamic (MD) simulations were used to elucidate the effect of temperature on the properties of functionalized vesicle membranes. A plausible prebiotic system was selected, constituted by a model membrane bilayer from an equimolar mixture of long-chain fatty acids and fatty amines, and an octapeptide, KSPFPFAA, previously identified as an optimized functional peptide in an evolution experiment. This peptide tends to form the largest spontaneous aggregates at higher temperatures, thereby enhancing the pore-formation process and the eventual transfer of essential molecules in a prebiotic scenario. The analyses also suggest that peptide-amphiphile interactions affect the structural properties of the membrane, with a significant increase in the degree of interdigitation at the lowest temperatures under study.


Management of acute thromboembolic limb ischemia.
Acute arterial occlusion affecting the extremities remains a significant cause of death and limb loss. Our approach to the management of these patients has been selective, and it is based upon a clinical distinction between embolism and thrombosis. Patients with acute embolic occlusion are treated with prompt embolectomy. Patients with thrombosis are given a course of heparin therapy, followed by elective arterial repair if necessary. Deterioration of the limb is an indication for emergency reconstruction, and nonviable limbs are amputated early. This approach to treatment was assessed in a 1-year prospective study, involving 29 patients with embolism and 50 patients with thrombosis. The initial diagnosis was found to be incorrect for seven patients (8.9%). Of the patients with embolism, four died (13.8%) and three required amputation (10.4%). There were six deaths (12%) among the patients with thrombosis, but eleven required amputation (22%), and in seven of these amputation was the definitive treatment. We have concluded that the selective use of surgery is an appropriate method of treatment for patients with acute thromboembolic limb ischemia.


Glycosylphosphatidylinositol biosynthesis defects in Gpi11p- and Gpi13p-deficient yeast suggest a branched pathway and implicate gpi13p in phosphoethanolamine transfer to the third mannose.
Glycosylphosphatidylinositols (GPIs) are critical for membrane anchoring and intracellular transport of certain secretory proteins. GPIs have a conserved trimannosyl core bearing a phosphoethanolamine (EthN-P) moiety on the third mannose (Man-3) through which the glycolipid is linked to protein, but diverse GPI precursors with EthN-Ps on Man-1 and Man-2 have also been described. We report on two essential yeast genes whose products are required late in GPI assembly. GPI11 (YDR302w) encodes a homologue of human Pig-Fp, a protein implicated in the addition of EthN-P to Man-3. PIG-F complements the gpi11 deletion, but the rescued haploids are temperature sensitive. Abolition of Gpi11p or Pig-Fp function in GPI11 disruptants blocks GPI anchoring and formation of complete GPI precursors and leads to accumulation of two GPIs whose glycan head groups contain four mannoses but differ in the positioning and number of side chains, probably EthN-Ps. The less polar GPI bears EthN-P on Man-2, whereas the more polar lipid has EthN-P on Man-3. The latter finding indicates that Gpi11p is not required for adding EthN-P to Man-3. Gpi13p (YLL031cp), a member of a family of phosphoryltransferases, is a candidate for the enzyme responsible for adding EthN-P to Man-3. Depletion of Gpi13p in a Gpi11p-defective strain prevents formation of the GPI bearing EthN-P on Man-3, and Gpi13p-deficient strains accumulate a Man(4)-GPI isoform that bears EthN-P on Man-1. We further show that the lipid accumulation phenotype of Gpi11p-deficient cells resembles that of cells lacking Gpi7p, a sequence homologue of Gpi13p known to add EthN-P to Man-2 of a late-stage GPI precursor. This result suggests that in yeast a Gpi11p-deficiency can affect EthN-P addition to Man-2 by Gpi7p, in contrast to the Pig-Fp defect in mammalian cells, which prevents EthN-P addition to Man-3. Because Gpi11p and Pig-Fp affect EthN-P transfer to Man-2 and Man-3, respectively, these proteins may act in partnership with the GPI-EthN-P transferases, although their involvement in a given EthN-P transfer reaction varies between species. Possible roles for Gpi11p in the supply of the EthN-P donor are discussed. Because Gpi11p- and Gpi13p-deficient cells accumulate isoforms of Man(4)-GPIs with EthN-P on Man-2 and on Man-1, respectively, and because the GPIs that accumulate in Gpi11p-defective strains are likely to have been generated independently of one another, we propose that the yeast GPI assembly pathway is branched.


Diagnoses of Dizziness- and Vertigo-related Disorders in ENT Practices in Germany.
The aim of this study was to analyze the prevalence of dizziness- and vertigo-related diagnoses in ear, nose, and throat (ENT) practices in Germany and the associated demographic characteristics based on data from a representative nationwide practice database. The study sample included patients from 138 ENT practices in Germany who received dizziness- and vertigorelated diagnoses (ICD-10 code) between January 2012 and December 2015. Collected parameters included age, sex, insurance status, prescribed medication (anatomical therapeutic chemical [ATC] class), and referrals to other specialists and hospitals. A total of 107,458 patients were available for analysis. Most common diagnoses were "dizziness and giddiness" (67.7%), "benign paroxysmal vertigo" (10.2%) and "disorder of vestibular function, unspecified" (7.2%). Referrals and admissions were made in 12.8%, mostly to radiologists (7.7%), followed by neurologists (3.7%), and hospitals (1.4%). Most referrals were made for unspecific diagnoses and for "vestibular neuronitis." The rate of medical prescriptions was 37.3%, with the most common prescription being for antivertigo preparations. Dizziness- and vertigo-related disorders are frequently diagnosed in ENT practices in Germany. The majority of these diagnoses are unspecific and lead to an increased rate of referrals and hospital admissions. The medical prescription rate, especially of antivertigo preparations, was high, even among patients with benign paroxysmal positioning vertigo. This study reflects a mostly pragmatic approach to a complex diagnostic and therapeutic challenge in daily ENT practice as well as the limited ability of the ICD-10 system to classify the underlying etiology.


An integrative review of care networks for adolescents who have experienced sexual violence.
Interventions aimed at children and adolescents who have suffered sexual violence should be coordinated across different services and include a range of actors if they are to ensure comprehensive, interdisciplinary and continuous care. Sexual violence against adolescents involves specific issues, such as the risk of pregnancy, abortion, the right to emergency contraception, and the difficulty some people have in discerning between violence and consent. The objective of this study was to identify and analyze national literature on care networks for adolescents who have experienced sexual violence. We conducted an integrative literature review, performing a content analysis of 11 articles focusing on the following five thematic categories: concepts of networks, network-based care services, network-based care practices, difficulties in implementing network-based care, and proposals for network-based care. Few of the analyzed articles presented a definition of care networks or described how they work. The findings show that literature focusing specifically on care networks for adolescents who have experienced sexual violence is scarce. Finally, it was noted that few articles discussed the role of the family, health regions and other potentially important actors in care networks.


The relationship between physical activity, clinical and cognitive characteristics and BDNF mRNA levels in patients with severe mental disorders.
Background: Here we aimed to clarify the association of physical activity with cognitive function and current mood in severe mental disorders in the most extensive sample to date. Secondly, we aimed to investigate the relationship between physical activity and BDNF mRNA levels.Methods: Three hundred and six patients with a DSM-IV schizophrenia (SZ) or bipolar disorder (BD) spectrum diagnosis were included. Clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV. Depressive symptomatology was measured using the Inventory of Depressive Symptoms (IDS-C) and the Calgary Depression Scale for Schizophrenia (CDSS). All patients underwent neuropsychological assessment. Physical activity was measured as hours spent on any regular physical activity (≥ or ˂90 min) per week. BDNF mRNA was measured in plasma using standardised procedures.Results: Patients with ≥90 min of physical activity per week had fewer depressive symptoms (P ˂0.001, Cohen's d = 0.48) and performed significantly better on working memory (P ˂ 0.001, d = 0.44) and executive functioning tasks (P ˂ 0.001, d = 0.50) compared to the ˂90-min group. BDNF mRNA was positively associated with physical activity (P = 0.046) and cognitive functioning (P = 0.037).Conclusions: Our study suggests a positive association between self-reported physical activity, cognitive function, mood and BDNF mRNA levels in severe mental disorders.


Deviation from Clinical Routines Can Reveal Sources of Device Design Vulnerability.
The ability to adequately ventilate a patient is critical and sometimes a challenge in the emergency, intensive care, and anesthesiology settings. Commonly, initial ventilation is achieved through the use of a face mask in conjunction with a bag that is manually squeezed by the clinician to generate positive pressure and flow of air or oxygen through the patient's airway. Large or small erroneous openings in the breathing circuit can lead to leaks that compromise ventilation ability. Standard procedure in anesthesiology is to check the circuit apparatus and oxygen delivery system prior to every case. Because the face mask itself is not a piece of equipment that is associated with a source of leak, some common anesthesia machine designs are constructed such that the circuit is tested without the mask component. We present an example of a leak that resulted from complete failure of the face mask due to a tiny tear in its cuff by the patient's sharp teeth edges. This subsequently prevented formation of a seal between the face mask and the patient's face and rendered the device incapable of generating the positive pressure it is designed to deliver. This instance depicts the broader lesson that deviation from clinical routines can reveal unappreciated sources of vulnerability in device design.


Role of leukocyte-derived pro-opiomelanocortin peptides in endotoxic shock.
The immune and neuroendocrine systems communicate and maintain homeostasis through various mechanisms, including the use of common signal and recognition molecules and the use of similar processes. This type of integrated network has profound effects on the onset and outcome of certain disease states, including endotoxic shock, in which a cascade of mediators influence the pathophysiologic responses. We have found that some of the common signal molecules shared between the immune and neuroendocrine systems are the peptide hormones adrenocorticotropin (ACTH) and endorphins (END). Our investigations have shown that these molecules are produced in vitro by cells of the immune system treated with various stimuli, including immunological stimuli such as bacterial lipopolysaccharide (LPS; endotoxin), virus infection (Newcastle virus; NDV), and the more classical neuroendocrine stimuli corticotropin-releasing hormone (CRH). We have proposed that the production of END by the peripheral immune system contributes to the pool of opioid peptides associated with the pathophysiology of endotoxic shock. Lymphocytes from LPS-sensitive C3HeB/FeJ mice but not LPS-resistant C3H/HeJ mice produce END and ACTH both in vitro and in vivo after treatment with LPS. Purification of the in vitro produced LPS-induced END from B-lymphocyte spleen cells followed by injections into both LPS-sensitive and -resistant mice elicits changes in body temperature and respiration rate. The spleen cells from the LPS-sensitive mice process ACTH and END differently depending on the stimulus for induction and the cell type in which the processing takes place. CRH or virus induce ACTH 1-39 and beta-END, whereas inductions with LPS yield major products of ACTH 1-22 to 1-26 and gamma-END, products that are for the most part unique to the immune system. We have shown that LPS induces a novel protease that functions optimally at pH 5 to cleave ACTH 1-39 into ACTH 1-22 to 1-26. This enzyme is present in LPS, but not mock or CRH-induced B cells from LPS-sensitive mice. The LPS-resistant mice did not possess this enzyme and therefore produced only the high-molecular-weight pro-opiomelanocortin (POMC)-like molecule. The inability to produce ACTH and END, presumably by their inability to process the precursor, may account, in part, for their lack of response to the LPS. The POMC peptides also may play an indirect role in orchestrating the pathophysiologic response, since both ACTH and END were shown to induce tumor necrosis factor (TNF). Our data strongly suggest that lymphocyte POMC peptides ACTH and END are important mediators in the overall response to endotoxin.


Utilization management in a large managed behavioral health organization.
The utilization management process of a managed behavioral health organization was examined to determine the frequency and types of reviews and the extent to which rationing of service was achieved through the denial of services. A case study of the utilization management program of a large managed behavioral health organization was done. Information was gathered from claims for 1997, and utilization review data were drawn from 51 plans. Data were examined by review type and authorization actions. The utilization management program performed a total of 9, 639 reviews. The most common type was concurrent review for additional outpatient therapy visits (46 percent). The second most common type was concurrent facility review (12.9 percent). The vast majority of authorizations were approved at the level requested by the provider (91.8 percent). Very few services were denied (.8 percent) or approved at a level lower than requested by the provider (1.3 percent). Although concerns have been raised about the high denial rates of utilization management programs, this study found very low denial rates. Further studies are needed to determine the precise mechanisms used in utilization management programs to control utilization. In addition, the large number of reviews raises questions about the time and opportunity costs of the review process.


Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?
Carnitine palmitoyl transferase I (CPT1) catalyzes the transport of long-chain fatty acids into mitochondria for beta-oxidation. A link between CPT1 and apoptosis has been suggested on the basis of several experimental data. Nevertheless, results are contradictory about the effective role of CPT1 in cell survival control and cancer development. Conversely, Fatty acid synthase (FAS) enzyme, required for the synthesis of fatty acids, is found over-expressed in tumors and inhibition of FAS triggers apoptosis in human cancer cells. We have studied the tumor-specific modulation of CPT1 and FAS in human colorectal cancer (n = 11) and breast carcinomas (n = 24). CPT1 was significantly decreased in the cytoplasm of tumoral samples (p < or = 0.04), whereas FAS was increased (p < or = 0.04). A striking CPT1 nuclear localization was evident in the tumors (p < or = 0.04). In the nuclear environment the protein would modulate the levels of acetyl/acyl-CoA implicated in the regulation of gene transcription. At this purpose, we performed in vitro experiments using epithelial neoplastic (MCF-7, Caco-2, HepG2 cells) and non neoplastic cell lines (MCF-12F) confirming a nuclear localization of CPT1 protein exclusively in neoplastic cells. Moreover histone deacetylase (HDAC) activity showed significantly higher levels in nuclear extracts from neoplastic than from control cells. HDAC1 and CPT1 proteins coimmunoprecipitated in nuclear extracts from MCF-7 cells. The treatment with HDAC inhibitors such as trichostatin A and butyrate significantly decreased nuclear expression of CPT1 and its bond to HDAC1. We also identified the existence of CPT1A mRNA transcript variant 2 in MCF-7, beside to the classic isoform 1. The peculiar localization of CPT1 in the nuclei of human carcinomas and the disclosed functional link between nuclear CPT1 and HDAC1 propose a new role of CPT1 in the histonic acetylation level of tumors.


Genetics and genomics of autism spectrum disorder: embracing complexity.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by impairments in social communication and social interaction and the presence of repetitive behaviors and/or restricted interests. ASD has profound etiological and clinical heterogeneity, which has impeded the identification of risk factors and pathophysiological processes underlying the disorder. A constellation of (i) types of genetic variation, (ii) modes of inheritance and (iii) specific genomic loci and genes have all recently been implicated in ASD risk, and these findings are currently being extended with functional analyses in model organisms and genotype-phenotype correlation studies. The overlap of risk loci between ASD and other NDDs raises intriguing questions around the mechanisms of risk. In this review, we will touch upon these aspects of ASD and how they might be addressed.


Geriatric oral health competency among dental providers.
Geriatrics as an educational topic has been a high priority in current health care. The innovative Age-Friendly health system with the 4Ms structure (what Matters most, Medication, Mentation, Mobility) needs to be integrated into oral health and dental services training. The purpose of this study is to respond to one question: are the graduating general dentists trained and prepared to treat medically vulnerable elderly in communities? All pre-doctorate dental students from first year to fourth year were invited to voluntarily respond to an online survey provided on Qualtrics. The survey provided examples of two broken molar teeth that need extraction. First, students were asked how comfortable they felt extracting the two molars based on the x-rays. Then, the question was repeated to evaluate if they felt comfortable with extracting the teeth in a patient with one chronic condition and related medication(s). Finally, the students were again questioned whether they feel comfortable to provide the same service to medically vulnerable patients with multiple health conditions and polypharmacy. The majority of students who participated in this study said they were comfortable with extracting the teeth of patients without any chronic condition. However, many more chose to refer medically vulnerable patients with multiple chronic conditions and polypharmacy to a specialist. Dental education in many U.S. dental schools may provide adequate education and create competent general dentists. Yet, the competency and confidence required for dentists to be able to treat older adults with multiple health conditions and using prescribed or over-the-counter medication is insufficient.


Miniature swine as an animal model in photodermatology: factors influencing sunburn cell formation.
Swine have played an important role as animal models in dermatological research. In order to evaluate the usefulness of pig skin in photodermatology, sunburn cell (SBC) formation in the epidermis of miniature swine and erythema production were studied. SBCs were readily formed in the epidermis of the swine by ultraviolet radiation. Suberythemal doses of broad-band UVB radiation were effective in producing SBCs, and there was a dose-response relationship between SBC formation and ultraviolet radiation. When SBC formation was related to ultraviolet radiation in terms of biological dose (i.e. minimal erythema dose) neither the spectral characteristics of the sources nor the degree of pigmentation in the skin affected the response. When SBC formation was related to physical dose (J/m2) the protection value of tanning was evident. These results, when coupled with the morphological and physiological similarities between human and porcine skin, demonstrate the usefulness of this animal model in photodermatology.


The effects of fatigue on robotic surgical skill training in Urology residents.
This study reports on the effect of fatigue on Urology residents using the daVinci surgical skills simulator (dVSS). Seven Urology residents performed a series of selected exercises on the dVSS while pre-call and post-call. Prior to dVSS performance a survey of subjective fatigue was taken and residents were tested with the Epworth Sleepiness Scale (ESS). Using the metrics available in the dVSS software, the performance of each resident was evaluated. The Urology residents slept an average of 4.07 h (range 2.5-6 h) while on call compared to an average of 5.43 h while not on call (range 3-7 h, p = 0.08). Post-call residents were significantly more likely to be identified as fatigued by the Epworth Sleepiness Score than pre-call residents (p = 0.01). Significant differences were observed in fatigued residents performing the exercises, Tubes and Match Board 2 (p = 0.05, 0.02). Additionally, there were significant differences in the total number of critical errors during the training session (9.29 vs. 3.14, p = 0.04). Fatigue in post-call Urology residents leads to poorer performance on the dVSS simulator. The dVSS may become a useful instrument in the education of fatigued residents and a tool to identify fatigue in trainees.


Cutaneous malignant melanoma metastatic to the vitreous.
A 38-year-old man previously had a cutaneous malignant melanoma excised from his right shoulder. He presented to our clinic with neovascular glaucoma, corneal edema, large pigmented keratic precipitates, anterior chamber reaction, and pigmented aggregates in the vitreous of his left eye. There were no other ocular findings. Subsequent enucleation was performed and the globe was studied histopathologically. Special stains and electron microscopy showed the presence of both macrophages and malignant melanin-producing cells within the vitreous. The diagnosis of cutaneous malignant melanoma metastatic to the vitreous was made based on these findings. This is a rarely reported clinical entity, for which a high index of suspicion should be maintained.


Novel IL-21 signaling pathway up-regulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas.
Interleukin-21 (IL-21), a member of the IL-2 cytokine family, has diverse regulatory effects on natural killer (NK), T, and B cells. In contrast to other cytokines that are usually immunostimulatory, IL-21 can induce apoptosis of murine B cells at specific activation-differentiation stages. This effect may be used for treatment of B-cell malignancies. Herein we report that diffuse large B-cell lymphoma (DLBCL) cell lines exhibit widespread expression of the IL-21 receptor (IL-21R) and that IL-21 stimulation leads to cell-cycle arrest and caspase-dependent apoptosis. IL-21 also induces apoptosis in de novo DLBCL primary tumors but does not affect viability of human healthy B cells. Furthermore, IL-21 promotes tumor regression and prolongs survival of mice harboring xenograft DLBCL tumors. The antilymphoma effects of this cytokine are dependent on a mechanism involving IL-21-activated signal transducer and activator of transcription 3 (STAT3) up-regulating expression of c-Myc. This up-regulation promotes a decrease in expression of antiapoptotic Bcl-2 and Bcl-X(L) proteins triggering cell death. Our results represent one of the first examples in which the STAT3-c-Myc signaling pathway, which can promote survival and oncogenesis, can induce apoptosis in neoplastic cells. Moreover, based on IL-21's potency in vitro and in animal models, our findings indicate that this cytokine should be examined in clinical studies of DLBCL.


New image-guided ultra-minimally invasive lumbar decompression method: the mild procedure.
Lumbar canal stenosis is a common source of chronic low back and leg pain. Minimally Invasive Lumbar Decompression (mild(R)) is a new minimally invasive treatment for pain relief from symptomatic central lumbar canal stenosis. The procedure involves limited percutaneous laminotomy and thinning of the ligamentum flavum in order to increase the critical diameter of the stenosed spinal canal. The objective of this technical report is to evaluate the acute safety of the mild procedure. Manual and electronic chart survey was conducted by 14 treating physicians located in 9 U.S. states on 90 consecutive patients who underwent the mild procedure. Patients within local geographical practice areas were selected in keeping with product Instructions For Use. Those patients requiring lumbar decompression via tissue resection at the perilaminar space, within the interlaminar space and at the ventral aspect of the lamina were treated. Data collected included any complications and/or adverse events occurring during or immediately following the procedure prior to discharge. Of 90 procedures reviewed, there were no major adverse events or complications related to the devices or procedure. No incidents of dural puncture or tear, blood transfusion, nerve injury, epidural bleeding, or hematoma were observed. Data were not specifically collected; however, regardless of difficulty, in this series none of the procedures were aborted and none resulted in adverse events. Efficacy parameters were not collected in this safety survey. This review demonstrates the acute safety of the mild procedure with no report of significant or unusual patient complications. To establish complication frequency and longer-term safety profile associated with the treatment, additional studies are currently being conducted. Survey data on file at Vertos Medical, Inc.


Simian hepatitis A virus (HAV) strain AGM-27: comparison of genome structure and growth in cell culture with other HAV strains.
Fragments of cDNA representing greater than 99% of the entire genome of wild-type hepatitis A virus (HAV) strain AGM-27, isolated from an African green monkey, were obtained by the polymerase chain reaction and sequenced. Comparison with other HAV isolates revealed differences in the predicted amino acid sequence in functionally critical parts of the genome. Comparison of the biological properties of AGM-27 with those of human wild-type and cell culture-adapted HM-175 strains revealed that AGM-27 grew in cell culture significantly better than did wild-type HM-175, but not as well as cell culture-adapted HM-175. AGM-27 and cell culture-adapted HM-175 were distinguishable by their differential growth in CV-1, FRhK-4 and primary AGMK cells.


Heat stress induces proteomic changes in the liver and mammary tissue of dairy cows independent of feed intake: An iTRAQ study.
Heat stress decreases milk yield and deleteriously alters milk composition. Reduced feed intake partially explains some of the consequences of heat stress, but metabolic changes in the mammary tissue and liver associated with milk synthesis have not been thoroughly evaluated. In the current study, changes of protein abundance in the mammary tissue and liver between heat-stressed cows with ad libitum intake and pair-fed thermal neutral cows were investigated using the iTRAQ proteomic approach. Most of the differentially expressed proteins from mammary tissue and liver between heat-stressed and pair-fed cows were involved in Gene Ontology category of protein metabolic process. Pathway analysis indicated that differentially expressed proteins in the mammary tissue were related to pyruvate, glyoxylate and dicarboxylate metabolism pathways, while those in the liver participated in oxidative phosphorylation and antigen processing and presentation pathways. Several heat shock proteins directly interact with each other and were considered as central "hubs" in the protein interaction network. These findings provide new insights to understand the turnover of protein biosynthesis pathways within hepatic and mammary tissue that likely contribute to changes in milk composition from heat-stressed cows.


Host range of Cercospora apii and C. beticola and description of C. apiicola, a novel species from celery.
The genus Cercospora is one of the largest and most heterogeneous genera of hyphomycetes. Cercospora species are distributed worldwide and cause Cercospora leaf spot on most of the major plant families. Numerous species described from diverse hosts and locations are morphologically indistinguishable from C. apii and subsequently are referred to as C. apii sensu lato. The importance and ecological role that different hosts play in taxon delimitation and recognition within this complex remains unclear. It has been shown that Cercospora leaf spot on celery and sugar beet are caused respectively by C. apii and C. beticola, both of which are part of the C. apii complex. During this study we characterized a new Cercospora species, C. apiicola, which was isolated from celery in Venezuela, Korea and Greece. The phylogenetic relationship between C. apiicola and other closely related Cercospora species was studied with five different gene areas. These analyses revealed that the C. apiicola isolates cluster together in a well defined clade. Both C. apii and C. beticola sensu stricto form well defined clades and are shown to have wider host ranges and to represent distinct species.


Reaction of reindeer to obstructions and disturbances.
In Scandinavia, highways and railroads have not generally created obstructions to the movement of domesticated reindeer, although thousands of animals are killed each year in accidents. Some disruption in the movements of wild reindeer in Norway has been associated with the construction of a railroad and highway through an alpine plateau south of Trondheim. Hydroelectric projects have had the greatest detrimental effects on reindeer by flooding rangelands and obstructing migration routes. Special problems are created by the fluctuating water levels in reservoirs and rivers; efforts to mitigate the effects of these fluctuations have been only partially successful. Reindeer have strong traditions for migrating along specific routes, and realignment of these routes is extremely difficult. Conflicts of interest exist between reindeer herders and foresters. During their winter feeding, the deer damage young trees. The cutting of forests usually results in a deterioration of the area as a rangeland for reindeer. Herbicides used in forestry have been implicated in the death of some reindeer in Sweden, and research is now under way to determine the effects of herbicides on reindeer. The increased use of fences in reindeer husbandry in Scandinavia has emphasized the fact that reindeer behavior and characteristics of the terrain must be considered if fences are to be successful in directing or controlling the movements of reindeer. Herders now use snowmobiles instead of reindeer for transportation and herding, but the machines disturb the reindeer and must be used with discretion. Recent evidence indicates that large amounts of industrial waste in the atmosphere are carried from the British Isles and central Europe to Scandinavia, where they fall out in rain and snow. This has raised concern about the influence of the wastes on lichens, the main winter food supply of reindeer. Studies are now under way in Finland, Sweden, and Norway, through the International Biological Program, to determine the growth rates of the several lichen species that are important to reindeer.


Intranodal Palisaded Myofibroblastoma: A Diagnostic Differential for Inguinal Lymphadenopathy.
BACKGROUND Benign tumors of the lymph nodes are rare and are not usually considered in the differential diagnosis in cases of lymphadenopathy because reactive hyperplasia, lymphoma, and metastatic carcinoma are the most likely causes of enlarged nodes. Intranodal palisaded myofibroblastoma (IPM) is a very rare benign mesenchymal tumor of the lymph nodes most often affecting but not limited to the inguinal region, with up to 92 cases reported in the English literature. The cell of origin is the intranodal differentiated smooth muscle cell or myofibroblast. Although the pathophysiology of IPM remains unclear, theories about viral oncogenesis and mutational changes in the ß-catenin gene with subsequent abnormal expression of ß-catenin and cyclin D1 have been raised. CASE REPORT We report a case of IPM in a 48-year-old man who presented with a mass in the left groin, with inconclusive imaging. The typical histologic findings of smooth muscle actin, cyclin D1, and ß-catenin positive intranodal spindle cell proliferation with characteristic palisades, amianthoid fibers, collagenous bodies, lack of atypia, and very low mitotic count, together with characteristic profile on ancillary testing, confirmed the diagnosis. In addition to staining with smooth muscle actin, cyclin D1 and ß-catenin, immunohistochemical studies showed focal positivity with desmin, a finding previously reported in 2 of the published cases. Surgical excision is usually curative, with a 6% recurrence rate and no reported cases of locally aggressive disease or malignant transformation. CONCLUSIONS Although rare, IPM should be included in the differential diagnosis of isolated lymphadenopathy.


Approach to Obesity in the Older Population.
Until recently, weight loss in older obese people was feared because of ensuing muscle loss and frailty. Facing overall increasing longevity, high rates of obesity in older individuals (age ≥ 65 years) and a growing recognition of the health and functional cost of the number of obesity years, abetted by evidence that intentional weight loss in older obese people is safe, this approach is gradually, but not unanimously, being replaced by more active principles. Lifestyle interventions that include reduced but sufficient energy intake, age-adequate protein and micronutrient intake, coupled with aerobic and resistance exercise tailored to personal limitations, can induce weight loss with improvement in frailty indices. Sustained weight loss at this age can prevent or ameliorate diabetes. More active steps are controversial. The use of weight loss medications, particularly glucagon-like peptide-1 analogs (liraglutide as the first example), provides an additional treatment tier. Its safety and cardiovascular health benefits have been convincingly shown in older obese patients with type 2 diabetes mellitus. In our opinion, this option should not be denied to obese individuals with prediabetes or other obesity-related comorbidities based on age. Finally, many reports now provide evidence that bariatric surgery can be safely performed in older people as the last treatment tier. Risk-benefit issues should be considered with extreme care and disclosed to candidates. The selection process requires good presurgical functional status, individualized consideration of the sequels of obesity, and reliance on centers that are highly experienced in the surgical procedure as well as short-term and long-term subsequent comprehensive care and support.


Learning from public health and hospital resilience to the SARS-CoV-2 pandemic: protocol for a multiple case study (Brazil, Canada, China, France, Japan, and Mali).
All prevention efforts currently being implemented for COVID-19 are aimed at reducing the burden on strained health systems and human resources. There has been little research conducted to understand how SARS-CoV-2 has affected health care systems and professionals in terms of their work. Finding effective ways to share the knowledge and insight between countries, including lessons learned, is paramount to the international containment and management of the COVID-19 pandemic. The aim of this project is to compare the pandemic response to COVID-19 in Brazil, Canada, China, France, Japan, and Mali. This comparison will be used to identify strengths and weaknesses in the response, including challenges for health professionals and health systems. We will use a multiple case study approach with multiple levels of nested analysis. We have chosen these countries as they represent different continents and different stages of the pandemic. We will focus on several major hospitals and two public health interventions (contact tracing and testing). It will employ a multidisciplinary research approach that will use qualitative data through observations, document analysis, and interviews, as well as quantitative data based on disease surveillance data and other publicly available data. Given that the methodological approaches of the project will be largely qualitative, the ethical risks are minimal. For the quantitative component, the data being used will be made publicly available. We will deliver lessons learned based on a rigorous process and on strong evidence to enable operational-level insight for national and international stakeholders.