A prospective evaluation of Medizip in Nigeria.
In a one year period between April, 1997 and March 1998 we have carried out a randomized controlled prospective study to evaluate the outcome of Medizip Surgical Zipper technique in closing 50 surgical wounds in Nigeria. There were similar sex, age and wound distribution between the Medizip study group and the conventional (needle and thread) control group. The cosmetic outcome of scar was rated as good or bad. It was good if the emerging scar was a thin linear (< or = 2 mm wide) scar, and bad if the scar was a broad flat (> 2 mm wide) or a heap-up (hypertrophic or keloidal) scar. The cosmetic outcome of scar was good in 45 (90%) of the Medizip study group as compared with 22 (44%) of the conventional control group. The observed difference between the two groups was statistically significant (P < 0.05). We observed superficial wound infection in one (2%) of the Medizip study group as compared with 10 (20%) of the conventional control group. The results of our study clearly demonstrated that the use of Medizip surgical Zipper would be a superior technique of closing surgical wounds in terms of the cosmetic outcome of scars and associated problems.


Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons.
Neurotrophins influence the epigenetic shaping of the vertebrate nervous system by regulating neuronal numbers during development and synaptic plasticity. Here we attempt to determine whether these growth factors can also regulate neurotransmitter plasticity. As a model system we used the selection between noradrenergic and cholinergic neurotransmission by paravertebral sympathetic neurons. Developing sympathetic neurons express the neurotrophin receptors TrkA and TrkC, two highly related receptor tyrosine kinases. Whereas the TrkA ligand nerve growth factor (NGF) has long been known to regulate both the survival and the expression of noradrenergic traits in sympathetic neurons, the role of TrkC and of its ligand neurotrophin-3 (NT3) has remained unclear. We found that TrkC expression in the avian sympathetic chain overlaps substantially with that of choline acetyltransferase. In sympathetic chain explants, transcripts of the cholinergic marker genes choline acetyltransferase and vasoactive intestinal polypeptide were strongly enriched in the presence of NT3 compared with NGF, whereas the noradrenergic markers tyrosine hydroxylase and norepinephrine transporter were reduced. The transcription factor chicken achaete scute homolog 1 was coexpressed with cholinergic markers. The effects of NT3 are reversed and antagonized by NGF. They are independent of neuronal survival and developmentally regulated. These results suggest a role for NT3 as a differentiation factor for cholinergic neurons and establish a link between neurotrophins and neurotransmitter plasticity.


Ponseti treatment for clubfeet: an international perspective.
The purpose of this article is to acquaint the reader with the Ponseti method of clubfoot treatment and to describe the features of the technique that make it superior to other forms of clubfoot treatment. These features make the technique applicable across a wide spectrum of healthcare delivery systems on a truly international basis. The Ponseti method has proven to be successful around the globe, in both industrialized countries and developing nations. In many settings, nonphysician practitioners are primarily responsible for the casting phase of treatment, particularly in areas with a shortage of physicians. Internationally, researchers are effectively expanding the scope of clubfeet treated: older children, postsurgical recurrent deformities, and nonidiopathic clubfeet. The barriers that undermine the outcomes of a Ponseti clubfoot program are primarily poverty and noncompliance with the extended post-casting brace protocol. The Ponseti method should be considered the best treatment modality for all children with clubfeet. In the developing world, where most neglected clubfeet occur, emphasis should continue to be the training of practitioners and implementation of programs to reach all affected children. Research will continue to broaden the indications for the method.


[Sarcoidosis in a patient with Crohn disease].
Extra-intestinal manifestations of inflammatory bowel disease (Crohn's disease) are frequent although pulmonary signs are uncommon. We report the case of a patient with sarcoidosis and inflammatory bowel disease and discuss the common features of these two diseases.


Somatization and depression among former Soviet immigrants.
This study investigated the prevalence of pure and overlapping forms of somatization and depression in a sample of former Soviet immigrants and whether pure somatization or pure depression could be differentiated using the study variables. Study respondents completed a demographic questionnaire, the Demands of Immigration Scale, and the Symptom Checklist 90R. Respondents were classified as (a) neither depressed nor somatic, (b) only somatic, (c) only depressed, or (d) both depressed and somatic. Univariate analyses and logistical regression were used to compare these four groups and to predict the likelihood of being only depressed or only somatic. The four groups differed in terms of immigration demands, age, education, employment, and years in the U.S. A logistic regression analysis was able to classify 75% of the participants as only somatic or only depressed on the basis of certain demographic characteristics. Age, being unemployed and not looking for work, and not having a college education increased the risk of being somatic rather than depressed.


Evaluation and management of suspected retinal detachment.
Retinal detachment often is a preventable cause of vision loss. There are three types of retinal detachments: exudative, tractional, and rhegmatogenous. The most common type is rhegmatogenous, which results from retinal breaks caused by vitreoretinal traction. Risk factors for retinal detachment include advancing age, previous cataract surgery, myopia, and trauma. Patients typically will present with symptoms such as light flashes, floaters, peripheral visual field loss, and blurred vision. Early intervention facilitates prevention of retinal detachment after formation of retinal breaks and improves visual outcomes of retinal detachment surgery. Patients with acute onset of flashes or floaters should be referred to an ophthalmologist.


Impact of Short- and Long-Term Exposure to Elevated Seawater Pco2 on Metabolic Rate and Hypoxia Tolerance in Octopus rubescens.
AbstractMuch of the CO2 released by human activity into the atmosphere is dissolving into the oceans, making them more acidic. In this study we provide the first data on the short- and long-term impacts of ocean acidification on octopuses. We measured routine metabolic rate (RMR) of Octopus rubescens at elevated CO2 pressure (Pco2) with no prior acclimation and 1 or 5 wk of acclimation and critical oxygen pressure (Pcrit) after 5 wk of acclimation. Our results show that with no prior acclimation, octopuses had significantly higher RMRs in 1,500-μatm Pco2 environments than octopuses in 700- or 360-μatm environments. However, after both 1 and 5 wk of acclimation there was no significant difference in RMRs between octopuses at differing Pco2, indicating that octopuses acclimated rapidly to elevated Pco2. In octopuses acclimated for 5 wk at 1,500 μatm Pco2, we observed impaired hypoxia tolerance, as demonstrated by a significantly higher Pcrit than those acclimated to 700 μatm Pco2. Our findings suggest that O. rubescens experiences short-term stress in elevated Pco2 but is able to acclimate over time. However, while this species may be able to acclimate to near-term ocean acidification, compounding environmental effects of acidification and hypoxia may present a physiological challenge for this species.


Treatment patterns in essential tremor: Real-world evidence from a United Kingdom and France primary care database.
Essential tremor (ET) is one of the most common neurological disorders, but information on treatment pattern is still scant. The aim of this study was to describe the demographic and clinical characteristics, treatment patterns, and determinants of drug use in patients with newly diagnosed ET in France and the United Kingdom. Incident cases of ET diagnosed between January 1, 2015 and December 31, 2018 with 2 years of follow-up were identified by using The Health Improvement Network (THIN®) general practice database. During the follow-up, we assessed the daily prevalence of use and potential switches from first-line to second-line treatment or other lines of treatment. Logistic regression models were conducted to assess the effect of demographic and clinical characteristics on the likelihood of receiving ET treatment. A total of 2957 and 3249 patients were selected in the United Kingdom and France, respectively. Among ET patients, drug use increased from 12 months to 1 month prior the date of index diagnosis (ID). After ID, nearly 40% of patients received at least one ET treatment, but during follow-up drug use decreased and at the end of the follow-up approximately 20% of patients were still on treatment. Among treated patients, ≤10% maintained the same treatment throughout the entire follow-up, nearly 20% switched, and 40%-75% interrupted any treatment. Results from the multivariate analysis revealed that, both in France and the United Kingdom, patients receiving multiple concomitant therapies and affected by psychiatric conditions were more likely to receive an ET medication. This study shows that ET is an undertreated disease with a lower-than-expected number of patients receiving and maintaining pharmacological treatment. Misclassification of ET diagnosis should be acknowledged; thus, results require cautious interpretation.


Spatial Segregation of Phosphatidylinositol 4,5-Bisphosphate (PIP(2)) Signaling in Immune Cell Functions.
Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is a prevalent phosphoinositide in the inner leaflet of the plasma membrane. PIP(2) associates with an ever-growing list of proteins, and participates in a variety of cellular processes. PIP(2) signaling to the actin cytoskeleton transduces specific signals necessary for changes in morphology, motility, endocytosis, exocytosis, phagocytosis, and cell activation. The mechanism(s) by which PIP(2) signaling pathways are specific is a topic of intense investigation. One working model is the compartmentalization of PIP(2)-mediated signaling by concentrating PIP(2) in cholesterol-dependent membrane rafts, therefore providing spatial and temporal regulation. Here we discuss properties of PIP(2) signaling to the actin cytoskeleton in immune cell functioning, the association of PIP(2) cellular pools with membrane rafts, and recent work investigating models for compartmentalization of PIP(2)-mediated signaling in membrane rafts to the actin cytoskeleton.


Live Attenuated Influenza Vaccine contains Substantial and Unexpected Amounts of Defective Viral Genomic RNA.
The live attenuated influenza vaccine FluMist® was withdrawn in the USA by the Centers for Disease Control and Prevention after its failure to provide adequate protective immunity during 2013-2016. The vaccine uses attenuated core type A and type B viruses, reconfigured each year to express the two major surface antigens of the currently circulating viruses. Here Fluenz™ Tetra, the European version of this vaccine, was examined directly for defective-interfering (DI) viral RNAs. DI RNAs are deleted versions of the infectious virus genome, and have powerful biological properties including attenuation of infection, reduction of infectious virus yield, and stimulation of some immune responses. Reverse transcription polymerase chain reaction followed by cloning and sequencing showed that Fluenz™ vaccine contains unexpected and substantial amounts of DI RNA arising from both its influenza A and influenza B components, with 87 different DI RNA sequences identified. Flu A DI RNAs from segment 3 replaced the majority of the genomic full-length segment 3, thus compromising its infectivity. DI RNAs arise during vaccine production and non-infectious DI virus replaces infectious virus pro rata so that fewer doses of the vaccine can be made. Instead the vaccine carries a large amount of non-infectious but biologically active DI virus. The presence of DI RNAs could significantly reduce the multiplication in the respiratory tract of the vaccine leading to reduced immunizing efficacy and could also stimulate the host antiviral responses, further depressing vaccine multiplication. The role of DI viruses in the performance of this and other vaccines requires further investigation.


Demographic trends of sick leave absenteeism among civil service employees at a federal agency from 2004 to 2012.
To investigate the associations between demographic variables and sick leave use. We analyzed sick leave use among civil servants at a federal agency (FA) from 2004 to 2012 by demographic and FA-specific variables. We used a mixed methods approach and type III analysis to build a descriptive model of sick leave proportions and demographic variables. Sick absenteeism usage varied significantly (variation of greater than one sick day per year) by sex, Emergency Operations Center response tier, length of service at the FA, age, and general schedule pay grade level. Our final descriptive model contained age, sex, response tier and an interaction term between age and sex. Future studies should examine these associations on smaller time scales, perhaps breaking the data down by month or day of the week.


Time to detoxify medical literature from guideline overdose.
The current financial turmoil in the United States has been attributed to multiple reasons including healthcare expenditure. Health care spending has increased from 5.7 percent of the gross domestic product (GDP) in 1965 to 16 percent of the GDP in 2004. Healthcare is driven with a goal to provide best possible care available at that period of time. Guidelines are generally assumed to have the high level of certainty and security as conclusions generated by the conventional scientific method leading many clinicians to use guidelines as the final arbiters of care. To provide the standard of care, physicians follow guidelines, proposed by either groups of physicians or various medical societies or government organizations like National Comprehensive Cancer Network. This has lead to multiple tests for the patient and has not survived the test of time. This independence leads to lacunae in the standardization of guidelines, hence flooding of literature with multiple guidelines and confusion to patients and physicians and eventually overtreatment, inefficiency, and patient inconvenience. There is an urgent need to restrict articles with Guidelines and develop some strategy like have an intermediate stage of pre-guidelines and after 5-10 years of trials, a systematic launch of the Guidelines. There can be better ways than this for putting together guidelines as has been suggested by multiple authors and researchers.


Anti-Inflammatory Potential of Seasonal Sonoran Propolis Extracts and Some of Their Main Constituents.
Biological properties of Sonoran propolis (SP) are influenced by harvest time. Caborca propolis showed cellular protective capacity against reactive oxygen species, which might be implicated in anti-inflammatory effects. However, the anti-inflammatory activity of SP has not been investigated so far. This study investigated the anti-inflammatory activity of previously characterized seasonal SP extracts (SPE) and some of their main constituents (SPC). The anti-inflammatory activity of SPE and SPC was evaluated by measuring nitric oxide (NO) production, protein denaturation inhibition, heat-induced hemolysis inhibition, and hypotonicity-induced hemolysis inhibition. SPE from spring, autumn, and winter showed a higher cytotoxic effect on RAW 264.7 cells (IC50: 26.6 to 30.2 µg/mL) compared with summer extract (IC50: 49.4 µg/mL). SPE from spring reduced the NO secretion to basal levels at the lowest concentration tested (5 µg/mL). SPE inhibited the protein denaturation by 79% to 100%, and autumn showed the highest inhibitory activity. SPE stabilized erythrocyte membrane against heat-induced and hypotonicity-induced hemolysis in a concentration-dependent manner. Results indicate that the flavonoids chrysin, galangin, and pinocembrin could contribute to the anti-inflammatory activity of SPE and that the harvest time influences such a property. This study presents evidence of SPE pharmacological potential and some of their constituents.


Unpolarized emissivity of thin oil films over anisotropic Gaussian seas in infrared window regions.
In this paper, we derive the unpolarized infrared (IR) emissivity of thin oil films over anisotropic Gaussian seas from a refined physical surface spectrum model of damping due to oil. Since the electromagnetic wavelength is much smaller than the surface mean curvature radius and than the surface root mean square height, the Kirchhoff-tangent plane approximation, reduced to the geometric optics approximation, can be used. The surface can then be replaced by its local infinite tangent plane at each point of each rough surface. The multiple reflections at each interface are ignored (i.e., for both the upper air/oil interface and the lower oil/sea interface of the contaminated sea). Nevertheless, the multiple reflections between the upper and the lower interfaces of the oil film are taken into account, by assuming a locally flat and planar thin oil film, which forms a local Fabry-Perot interferometer. This means that the Fresnel reflection coefficient of a single interface can be substituted for the equivalent Fresnel reflection coefficient of the air/oil/sea film, calculated by considering an infinite number of reflections inside the layer. Comparisons of the emissivity between a clean sea and a contaminated sea are presented, with respect to emission angle, wind speed, wind direction, oil film thickness, oil type, and wavelength. Thus, oil detection, characterization, and quantization are investigated in the IR window regions.


Information systems for general practitioners for quality assessment: I. Responses of the doctors.
A questionnaire was sent to all general practitioner principals in Leicestershire and Lincolnshire (n = 669) to determine (a) the extent to which they would participate in quality assessment activities based on objective evidence of performance and (b) the personal and professional characteristics of interested doctors. The overall response rate to the questionnaire was 76% (508 replies). The highest response rates were recorded by trainers (100%), principals in training practices (94%), and younger doctors (80-86%), the lowest by overseas graduates (59%) and older doctors (65%). Distinctive patterns of interest and participation in three types of audit activities were clearly evident. Overall, 61% (310) of respondents wished to be provided with profiles of practice activity from their family practitioner committees, 36% (183) volunteered to participate in a prescribing study, and 34% (172) expressed interest in carrying out an audit in depth. Proportionately, the most enthusiastic and active groups were trainers 88%, 70%, 62%), principals in training practices (74%, 49%, 47%), and members or fellows of the Royal College of General Practitioners (71%, 50%, 45%). Also active were younger doctors, vocationally trained doctors, and principals in large group practices. These figures suggest that roughly 15 000 general practitioners in the United Kingdom would be prepared to participate in performance review activities using information provided by external agencies, 10 000 would if they had to generate some of the information, and 7500 would if they had to produce all the information themselves.


Inhibition of suicidal erythrocyte death by blebbistatin.
Blebbistatin, a myosin II inhibitor, interferes with myosin-actin interaction and microtubule assembly. By influencing cytoskeletal dynamics blebbistatin counteracts apoptosis of several types of nucleated cells. Even though lacking nuclei and mitochondria, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include energy depletion and osmotic shock, which enhance cytosolic Ca(2+) activity with subsequent Ca(2+)-sensitive cell shrinkage and cell membrane scrambling. The present study explored the effect of blebbistatin on eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in fluorescence-activated cell sorting analysis and cytosolic Ca(2+) concentration from Fluo3 fluorescence. Exposure to blebbistatin on its own (1-50 μM) did not significantly modify cytosolic Ca(2+) concentration, forward scatter, or annexin V binding. Glucose depletion (48 h) was followed by a significant increase of Fluo3 fluorescence and annexin V binding, effects significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 10 μM). Osmotic shock (addition of 550 mM sucrose) again significantly increased Fluo3 fluorescence and annexin binding, effects again significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 25 μM). The present observations disclose a novel effect of blebbistatin, i.e., an influence on Ca(2+) entry and suicidal erythrocyte death following energy depletion and osmotic shock.


The use of multiple endpoints to define the mechanism of action of reproductive toxicants and germ cell mutagens.
Although a variety of endpoints are routinely assessed in reproductive toxicity studies, the inclusion of additional (and potentially more sensitive) endpoints may increase our ability to detect adverse effects on male or female reproduction and also provide information pertaining to the mechanism of action of the reproductive toxicant. Methyl chloride (MeCl) is a well characterized reproductive toxicant in the male rat, and can serve as a model to illustrate the importance of using multiple endpoints to determine the biological basis of chemically induced toxicity in the reproductive system. Exposure of male rats to MeCl results in bilateral testicular degeneration and epididymal inflammation and sperm granuloma formation. Females bred to these males in a dominant lethal assay exhibit elevated rates of postimplantation embryonic death during the first 2 weeks after treatment and increased preimplantation embryonic loss during weeks 2 to 8 post-exposure. Since the chemical is known to be a direct-acting mutagen in vitro and a kidney carcinogen in vivo, the increased embryo death rate observed might reasonably be considered good evidence that MeCl is a direct-acting germ cell mutagen. However, subsequent investigations revealed that MeCl-induced preimplantation loss was a result of cytotoxic rather than genotoxic effects on sperm, with a significant decrease in the count of motile sperm of normal morphology in exposed males during weeks 2 to 8 after treatment. In fact, examination of the fertilization rate during these weeks using a system of embryo recovery and culture revealed that the entire elevated rate of preimplantation loss detected in the dominant lethal assay was the result of failure of fertilization; it had no genetic component at all. Postimplantation death is considered a more reliable indicator of dominant lethality than is preimplantation loss. In the MeCl dominant lethal assay, such increased postimplantation loss was detected only when the fertilizing sperm had been present at the site of MeCl-induced acute inflammation in the cauda epididymis. Inflammatory cells, such as those in the MeCl-exposed epididymis, are known to produce a variety of genetic lesions in the DNA of neighboring cells. Therefore, male rats were concurrently exposed to MeCl and treated with an anti-inflammatory agent (BW755C) to inhibit the epididymal inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)


Genome-wide scan for blood pressure in Australian and Dutch subjects suggests linkage at 5P, 14Q, and 17P.
Large-scale studies estimate the heritability of blood pressure at approximately 50%. We carried out a genome-wide linkage analysis to search for chromosomal loci that might explain this heritability using longitudinal, multiple measures of systolic and diastolic blood pressure obtained in sibling pairs and dizygotic twin pairs from 2 countries (a total of 286 pairs from Australia and 636 pairs from the Netherlands). These pairs and a large number of their parents were genotyped with microsatellite markers. Multivariate linkage analysis of the combined data of both countries, using a variance components approach, showed suggestive linkage for diastolic blood pressure on chromosomes 5p13.1 (logarithm of odds score: 2.48), 14q12 (logarithm of odds score: 2.40) and 17q24.3 (logarithm of odds score: 2.36). The highest logarithm of odds score of 1.21 for systolic blood pressure was observed on chromosome 13q34. These results replicate earlier findings and add to a slowly emerging picture of multiple loci contributing to quantitative blood pressure variation.


[Multimedia learning program for medical consultation].
To improve communicative competence during physicians' consultations, we developed a computer-assisted multimedia learning programme. This programme can be used in medical education as well as in continuing education for physicians. Dependent on individual skills and needs, the system, based on hypertext links, can be tailored to expand and improve communicative competence in a series of steps. The programme is based on a manual of medical interviewing and breaking bad news. The user gains information about theory and techniques of verbal intervention. He is trained to be able to reflectively observe and interactively intervene in video-taped and transcribed physician-patient dialogues. In a contrast-typological approach to model learning, in which negative and positive cases can be compared in a problem-based concept, alternative types of interventions can be recognised and evaluated. Finally, the learning goals in verbal intervention techniques should be subject of self-evaluation which can be objectified by further evaluations.


Association of social and cognitive impairment and biomarkers in autism spectrum disorders.
The neurological basis for autism is still not fully understood, and the role of the interaction between neuro-inflammation and neurotransmission impairment needs to be clearer. This study aims to test the possible association between impaired levels of gamma aminobutyric acid (GABA), serotonin, dopamine, oxytocin, and interferon-γ-induced protein-16 (IFI16) and the severity of social and cognitive dysfunctions in individuals with autism spectrum disorders. GABA, serotonin, dopamine, oxytocin, and IFI16 as biochemical parameters related to neurochemistry and inflammation were determined in the plasma of 52 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) or social responsiveness scale (SRS), and compared to 30 age- and gender-matched control samples. The data indicated that Saudi patients with autism have remarkably impaired plasma levels of the measured parameters compared to age and gender-matched controls. While serotonin in platelet-free plasma and dopamine did not correlated with the severity in social and cognitive dysfunction, GABA, oxytocin, and IFI16 were remarkably associated with the severity of both tested scores (SRS and CARS). The relationship between the selected parameters confirms the role of impaired neurochemistry and neuro-inflammation in the etiology of autism spectrum disorders and the possibility of using GABA, oxytocin, and IFI16 as markers of autism severity. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of clinical symptoms and provide significant guidance for future therapeutic strategy to re-establish physiological homeostasis.


Activity-dependent synaptic plasticity and metaplasticity in spinal motor networks.
Throughout life, neuronal network properties are modulated according to both external and internal stimuli. These adaptive capabilities of the central nervous system (CNS) have been generically termed "plasticity". One prominent form of CNS plasticity is the capability of synapses to change their strength. Synaptic strength is not a constant value but depends at each moment on the synapse's past activity. These changes in transmission efficacy are called activity-dependent synaptic plasticity (ADSP) and result in an increase (potentiation) or a decrease (depression) in synaptic strength. The ability of synapses to express one type of ADSP can change as a function of previous plasticity and previous activation of synapses. This plasticity of synaptic plasticity has been termed metaplasticity. ADSP and metaplasticity are now regarded as essential mechanisms for normal information processing in neuronal networks. Rhythmic activities such as locomotion are generated by rhythmically active central neuronal networks called central pattern generators (CPGs) that possess the intrinsic ability to generate rhythmic and organized activity in the absence of sensory inputs. The CPG activity arises from a complex dynamic interaction between synaptic transmission, intrinsic membrane properties and neuromodulatory inputs. A growing body of evidence suggests that the spinal cord matches the plastic and metaplastic properties found in other parts of the CNS, both under normal conditions and after spinal cord injury. Here, findings describing ADSP and its neuromodulation in vertebrate sensorimotor networks are reviewed, followed by a discussion of the potential role of ADSP and neuromodulation in the physiology and pathophysiology of motor circuit assembly.


Delayed ACL Reconstruction in Patients ≥40 Years of Age Is Associated With Increased Risk of Medial Meniscal Injury at 1 Year.
Anterior cruciate ligament (ACL) tears in the pediatric and young adult ACL-deficient knee are often associated with meniscal or chondral injury with delayed time to surgery. The incidence of ACL reconstruction performed in patients aged ≥40 years is rising, and it is unclear if delayed surgery in this cohort similarly affects the health of the meniscus and cartilage. To evaluate whether delayed reconstruction in a cohort of patients aged ≥40 years is associated with an increased risk of meniscal or chondral injury. Cohort study; Level of evidence, 3. Records of patients aged ≥40 years who underwent primary arthroscopic ACL reconstruction between 2012 and 2016 at an academic hospital were retrospectively reviewed. Patient characteristic data and time to surgery were recorded. Operative reports were analyzed for meniscal and chondral injuries as well as treatment. Patients were grouped according to time to surgery, defined as early (<90 days) or delayed (≥90 days). Logistic regression modeling was used to form associations between elapsed time to surgery and patient characteristics to meniscal and chondral damage. Additionally, risks for meniscal and chondral injury were analyzed at time points of 180 days and 1 year from injury to surgery. A total of 227 patients met the study criteria: 106 patients underwent early surgery, and 121 underwent delayed surgery. The authors identified 127 medial meniscal tears and 106 lateral meniscal tears. Medial, lateral, and patellofemoral compartment chondral injury was reported in 127, 82, and 130 patients, respectively. Delayed surgery (≥90 days) was not associated with increased risk of medial or lateral meniscal tears or any chondral injury at 90 days. Each year of increased age was associated with an increased odds ratio: 1.09 ( P = .001) for medial meniscal tears, 1.06 ( P = .014) for lateral meniscal tears, 1.10 ( P = .001) for medial compartment chondral injuries, and 1.07 ( P = .007) for patellofemoral compartment chondral injuries. Additionally, each unit of increased body mass index was associated with an increased odds ratio: 1.09 ( P = .039) for medial meniscal tears and 1.14 ( P = .003) for medial compartment cartilage injury. Analysis of 180-day and 1-year time points revealed an increased risk (odds ratio, 3.47; 95% CI, 1.55-7.77; P = .002) for medial meniscal injury when surgery was delayed for >1 year. Delayed ACL reconstruction (≥90 days) among patients aged ≥40 years was not associated with an increased risk of meniscal or chondral injury. Increasing age and body mass index were associated with higher risks of meniscal and chondral injuries in this cohort. Delay in surgery for >1 year was associated with increased risk of medial meniscal tear.


Implications of Neural Plasticity in Retinal Prosthesis.
Retinal degenerative diseases such as retinitis pigmentosa cause a progressive loss of photoreceptors that eventually prevents the affected person from perceiving visual sensations. The absence of a visual input produces a neural rewiring cascade that propagates along the visual system. This remodeling occurs first within the retina. Then, subsequent neuroplastic changes take place at higher visual centers in the brain, produced by either the abnormal neural encoding of the visual inputs delivered by the diseased retina or as the result of an adaptation to visual deprivation. While retinal implants can activate the surviving retinal neurons by delivering electric current, the unselective activation patterns of the different neural populations that exist in the retinal layers differ substantially from those in physiologic vision. Therefore, artificially induced neural patterns are being delivered to a brain that has already undergone important neural reconnections. Whether or not the modulation of this neural rewiring can improve the performance for retinal prostheses remains a critical question whose answer may be the enabler of improved functional artificial vision and more personalized neurorehabilitation strategies.


Hyaluronic acid in secretory otitis media. A biochemical study of mucoid middle-ear effusions and serum.
Middle-ear effusions of the mucoid type were collected from 14 children with secretory otitis media and analysed by a sensitive assay for hyaluronic acid. The concentration of the polysaccharide varied between three and 42 micrograms/g. in different patients but was in the same range in effusion material taken from the two ears of the same patient. As the hyaluronic acid concentrations were high compared to the serum levels, the results indicate that the effusion material contains a component derived from connective tissue.


[A curriculum based certification of competence in gynaecologic surgical oncology].
In France, we are lacking an identified pathway for training in gynaecological cancer surgery. The four competent French learned societies, the SFOG, the CNGOF, the SFCO and the SCGP, supported by the CNU of Obstetrics &Gynaecology- and UNICANCER, agreed to materialize this course and attest it by a certification awarded by a national jury. The national committee of certification in gynaecological oncology made up of 10 members, representing the 6 concerned organizations, set itself 5 objectives: the definition of the eligibility criteria for training centres; the determination of a check-list to be filled by the candidate; the determination of a targeted curriculum for the training in gynecological oncological surgery; the determination of the assets necessary for the certification of a candidate already in practice; and the practical organization of the certification. Criteria for approval of centres for training included 150 gynaecological cancer cases per year, among which 100 excisional surgeries, including 20 advanced-stage ovarian cancers. For certification of candidate who followed the curriculum established by the committee or by validation of prior experience for an actual practitioner, a candidate must validate a logbook and fill out a checklist including 4 parts: theoretical and practical training; research and publications; teaching and subscription to a continuing education program. The accomplished elements of the logbook and the checklist will be evaluated by a score. The first certification session is planned for the end of 2021. The optimisation of the surgical management of patients treated for gynaecological cancer is achieved through the identification of a training course and the certification, by a national jury, of the skills of surgeons who have completed it.


Lead isotopic composition of fly ash and flue gas residues from municipal solid waste combustors in France: implications for atmospheric lead source tracing.
Fly ash and flue gas residues from eight municipal solid waste combustors (MSWC) in France (1992--93 and 1998/ 2002) were analyzed for their Pb isotopic composition. Fly ashes are more representative of solid residual particles, whereas flue gas residues reflect mostly the composition of gas phases. Both sample types contain hundreds to thousands of micrograms of metals per gram. Leaching experiments showed that metals are present in condensed phases, probably as sulfates and chlorides, and suggest that Cd, Pb, and Zn are highly fractionated from one another during volatilization/condensation processes occurring during combustion. Although all the samples analyzed define a fairly restricted range in Pb isotopic compositions (206Pb/207Pb = 1.148-1.158 and 208Pb/206Pb = 2.101-2.114) compared to other environmental samples, some MSWC produce materials having distinct isotopic compositions, whereas others display very similar ones. Isotopic heterogeneity is also measured between samples from a single MSWC. This is interpreted as resulting from the heterogeneity of the waste source materials. The range of Pb isotopic composition of incinerator materials form a well-defined linear array in the 208Pb/206Pb versus 206Pb/207Pb diagram. This array is compatible with the previously reported European standard pollution (ESP) line and most probably represent the average lead isotopic composition of industrial atmospheric emissions in France, with the following ratios: 206Pb/207Pb = 1.154+/-0.003 and 208Pb/206Pb = 2.107+/-0.003 (1sigma).


microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer.
The aim of this study was to investigate the role of microRNA-21 (miR-21) in the regulation of phosphatase and tensin homolog deleted from chromosome-10 (PTEN) expression and proliferation of endometrioid endometrial cancer (EEC) cells. We performed a qRT-PCR assay with miR-21 and PTEN in 16 paired EEC tumor tissues and adjacent non-tumor endometrium. To investigate the regulation of PTEN by miR-21, we designed gain- and loss-of-function of miR-21 experiments in the KLE cell line by transfection with a synthetic miR-21 mimic and inhibitor. To validate the putative binding site of miR-21 in the 3' untranslated region (3'-UTR) of PTEN messenger RNA (mRNA), a dual-luciferase reporter assay was carried out. To evaluate the potential effect of miR-21 on EEC proliferation, we performed both overexpression experiments, using an miR-21 mimic, and inhibition assays, using an miR-21 inhibitor. miR-21 was overexpressed in EEC and was inversely correlated with PTEN protein expression (P<0.001). miR-21 regulated PTEN protein expression and cell proliferation in the KLE cell line and the direct binding of miR-21 to the PTEN 3'-UTR was confirmed using a dual-luciferase reporter assay. The upregulation of miR-21 led to a significant decrease in the PTEN protein expression level (P=0.007). The downregulation of miR-21 led to a significant increase in PTEN protein (P=0.002). The expression of luciferase in the wt-PTEN-3'-UTR-pGL3 group was downregulated in the presence of the miR-21 mimic (P=0.001). miR-21 was overexpressed in EEC. In conclusion, we demonstrated that the expression of PTEN protein, but not mRNA, was negatively directly regulated by miR-21 in the KLE cell line. The overexpression of miR-21 modulated EEC cell proliferation through the downregulation of PTEN.


Exploitation of ontological resources for scientific literature analysis: searching genes and related diseases.
Ontological resources such as controlled vocabularies, taxonomies and ontologies from the OBO foundry are used to represent biomedical domain knowledge. The development of such resources is a time consuming task. Once they are finished they contribute to standardization of information representation, interoperability of IT solutions, literature analysis and knowledge discovery. Text mining comprises IT solutions for information retrieval (IR) and information extraction (IE). IR technology exploits ontological resources to select documents that fit best to the processed query, for example, through indexing of the literature content with concept ids or through disambiguation of terms in the query. IE solutions make use of the ontological labels to identify concepts in the text. The text passages that denote conceptual entries are then used either to annotate named entities or to relate the named entities to each other. For knowledge discovery (KD) solutions the identified concepts in the scientific literature are used to relate entities to each other, e.g. to identify gene-disease relations based on shared molecular functions.


Polyethylene failure in New Jersey low-contact stress total knee arthroplasty.
From January 1985 to December 1990, 598 consecutive New Jersey low-contact stress (LCS) total knee arthroplasties (TKAs) were performed for gonarthrosis. Among these 598 operations, 322 were with rotating platform elements and 276 were with meniscal bearing elements. During 5 to 8 years of follow-up, eight knees had severe symptomatic polyethylene failure that required revision surgery; all eight cases were meniscal bearing types. The failed polyethylene inserts were retrieved and studied. It was observed that there were four probable failure mechanisms associated with the catastrophic polyethylene wear. First, insufficient thickness of the meniscal bearing was the major reason for wear. Second, the malpositioning of the metal tibial tray in the transverse plane resulted in the breaking of the meniscal bearing. Third, the inability of the patellar to rotate due to tissue ingrowth made the polyethylene break. Last, yellowing of the subsurface of the meniscal bearing was a sign of polyethylene failure. These four possible failure mechanisms are all associated with the design of the meniscal bearing type of LCS knee prostheses. Therefore, it is suggested that the design of the LCS knee prosthesis should be modified.


Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation.
The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.


Cancer Informatics for Cancer Centers: Scientific Drivers for Informatics, Data Science, and Care in Pediatric, Adolescent, and Young Adult Cancer.
Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues that we faced at our respective institutions and cancer centers. Here, we provide meeting highlights from the latest CI4CC Symposium, which was delayed from its original April 2020 schedule because of the COVID-19 pandemic and held virtually over three days (September 24, October 1, and October 8) in the fall of 2020. In addition to the content presented, we found that holding this event virtually once a week for 6 hours was a great way to keep the kind of deep engagement that a face-to-face meeting engenders. This is the second such publication of CI4CC Symposium highlights, the first covering the meeting that took place in Napa, California, from October 14-16, 2019. We conclude with some thoughts about using data science to learn from every child with cancer, focusing on emerging activities of the National Cancer Institute's Childhood Cancer Data Initiative.


Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases.
We identified functionally polarized subsets of CD4 memory T cells on the basis of the expression of CD11a, CD45RA and CD62L. Within the several phenotypically distinct subsets of CD4 memory cells are two that, upon stimulation, produce primarily IL-4 (MT(2), CD45RA(-)CD62L(+)CD11a(dim)) or primarily IFN-gamma (MT(1), CD45RA(-)CD62L(-)CD11a(bright)). In addition, four other phenotypically distinct subsets of CD4 cells have unique cytokine profiles. To determine the clinical relevance of the representation of these cell types, we analyzed blood from patients with the chronic diseases leprosy and atopy. These diseases are characterized as immunologically polarized, since T cell responses in affected individuals are often strongly biased towards T(h)1 (dominated by IFN-gamma production) or T(h)2 (IL-4 production). We show here that this polarization reflects homeostatic or differentiation mechanisms affecting the representation of the functionally distinct subsets of memory CD4 T cells, MT(1) and MT(2). Significantly, the representation of the MT(1) and MT(2) subsets differs dramatically between subjects with tuberculoid leprosy (a T(h)1 disease), or lepromatous leprosy or atopic disease (T(h)2 diseases). However, there was no difference in the cytokine profiles of these or any of the other finely resolved CD4 subsets, when compared between individuals across all disease states. Thus, it is the representation of these subsets in peripheral blood that is diagnostic of the polarized state of the immune system.


Evaluation of the relationship between neonatal serum asprosin levels and anthropometric measurements in newborns of mothers with and without gestational diabetes mellitus.
Asprosin is a newly identified adipokine that is expressed in the placenta. Its production is increased in women with gestational diabetes mellitus (GDM), and it is a factor related to insulin resistance. This study aimed to determine whether neonatal serum asprosin levels are associated with anthropometric characteristics of newborns born to mothers with and without GDM. This study included 51 newborns of mothers with GDM (insulin-treated or diet-treated) and 55 control newborns with their mothers. In newborns, anthropometric parameters were measured, and the concentrations of asprosin were detected by ELISA. Maternal blood glucose levels, body weight, and length were measured and body mass index (BMI) was calculated. Serum asprosin levels were significantly higher and linked to a higher risk in the newborns of mothers with GDM compared with those of the control newborns (170.3 [132.6] vs. 91.4 [68.7] ng/mL, p < 0.001). Serum asprosin levels were negatively correlated with blood glucose concentrations (r = -0.282, p = 0.045) in the newborns of mothers with GDM and significantly positively correlated with birth weight (r = 0.315, p = 0.019) in the control newborns. Newborn serum asprosin levels were positively correlated with the glucose levels (r = 0.264, p = 0.006) of all mothers. In addition, newborns born to an insulin-treated mother with GDM had significantly higher birth weight and length than newborns born to a diet-treated mother with GDM (3262.9 vs. 3137 g, p = 0.032, and 49.7 vs. 49.2 cm, p = 0.05). Although asprosin levels were higher in newborns of mothers treated with insulin, these differences were not statistically significant. Mothers with GDM had high blood glucose levels (p = 0.032). Serum levels of asprosin are increased and negatively correlated with glucose concentrations in newborns of mothers with GDM. Asprosin could be used as an early biomarker in newborns of GDM mothers.


Cytologic and bacteriologic evaluation of tracheobronchial aspirates from clinically normal foals.
Thirty-eight tracheobronchial aspirates (TBA) were collected from twenty 1 to 6-month-old foals, which were free of clinical signs of respiratory tract or other infectious disease. We collected TBA from 9 of the foals 3 times when they were approximately 8, 16, and 24 weeks old. Aspirates were examined cytologically after staining with modified Wright-Giemsa, Gram, toluidine blue, and prussian blue stains. Aerobic bacterial culturing was performed on all aspirates. Of the 20 initial TBA, 4 (20%) were normal cytologically on the basis of previously defined criteria for TBA from clinically normal horses, 6 (30%) had a high percentage of eosinophils (greater than 5%), 8 (40%) were classified as indicative of subacute inflammation, and 2 (10%) were classified as indicative of acute inflammation. Nine (45%) were positive for mast cells and none were positive for hemosiderin-laden macrophages (hemosiderophages). Of the 9 foals from which samples were collected at 16 and 24 weeks of age, results were similar, except for an increase in the number of TBA classified as indicative of chronic inflammation (33% and 22% respectively) and the number positive for hemosiderophages (33% and 88%, respectively). One TBA was considered nondiagnostic because of pharyngeal contamination. Culturing of 12 of the 37 aspirates (32%) yielded a potential microbial pathogen. Only 2 were positive cultures from the same foal. The following organisms were isolated: beta-hemolytic Streptococci spp (4), Actinobacillus/Pasteurella spp (4), Rhodococcus equi (2), unidentified nonenteric Gram-negative rod (1), and Escherichia coli (1). Thirty-four of the 37 aspirates (92%) yielded light growth of various organisms considered to be nonpathogenic and normal inhabitants of the upper respiratory tract.


Spinal cord protection during open repair of thoracic and thoracoabdominal aortic aneurysms using profound hypothermia and circulatory arrest.
Reduced risk of paraplegia is argued as an advantage of endovascular repair of descending thoracic aortic aneurysms (DTA) and thoracoabdominal aortic aneurysms (TAAA); however, paraplegia rates with open repair vary widely. We identified consecutive patients undergoing open repair of TAAA or DTA with or without arch replacement using profound hypothermia and circulatory arrest as a spinal cord protection strategy on a single surgical service between June 1, 2001 and September 20, 2010. Ninety-nine procedures were performed in 94 patients with a mean age of 59 years (range 19 to 84 years), 56 of whom were male (60%). The extent of repair was TAAA in 37 (Crawford extent I in 6, extent II in 28, and extent III in 3), DTA in 37, and DTA plus arch in 25. Surgery was urgent or emergent in 25 patients (25%). Operative mortality (30-day) was 10% (10 of 99), including a mortality of 12% for arch DTA (3 of 26), 11% for TAAA (4 of 25), and 5% for isolated DTA (2 of 37). There were 11 (11%) strokes and 11 patients experienced renal failure (7 with dialysis). There were 15 late deaths and survival at 5 years was 74% (95% CI, 62.4-88.2%). No patients experienced paraplegia, although one had delayed paraparesis thought to be secondary to refractory hypotension postoperatively. Although the mortality and stroke risks for patients undergoing repair of DTA or TAAA using profound hypothermia and circulatory arrest are substantial, the risk for paraplegia is low. In appropriately selected patients, profound hypothermia and circulatory arrest should be the preferred technique for spinal cord protection for DTA and TAAA.


Yeast surface display of full-length human microtubule-associated protein tau.
Microtubule-associated protein tau is an intrinsically disordered, highly soluble protein found primarily in neurons. Under normal conditions, tau regulates the stability of axonal microtubules and intracellular vesicle transport. However, in patients of neurodegeneration such as Alzheimer's disease (AD), tau forms neurofibrillary deposits, which correlates well with the disease progression. Identifying molecular signatures in tau, such as posttranslational modification, truncation, and conformational change has great potential to detect earliest signs of neurodegeneration and develop therapeutic strategies. Here, we show that full-length human tau, including the longest isoform found in the adult brain, can be robustly displayed on the surface of yeast Saccharomyces cerevisiae. Yeast-displayed tau binds to anti-tau antibodies that cover epitopes ranging from the N-terminus to the 4R repeat region. Unlike tau expressed in the yeast cytosol, surface-displayed tau was not phosphorylated at sites found in AD patients (probed by antibodies AT8, AT270, AT180, and PHF-1). However, yeast-displayed tau showed clear binding to paired helical filament (PHF) tau conformation-specific antibodies Alz-50, MC-1, and Tau-2. Although the tau possessed a conformation found in PHFs, oligomerization or aggregation into larger filaments was undetected. Taken together, yeast-displayed tau enables robust measurement of protein interactions and is of particular interest for characterizing conformational change.


Physiotherapy and intermittent positive-pressure ventilation of chronic bronchitis.
Patients aged over 45 admitted to hospital with exacerbations of chronic bronchitis alone or in association with cor pulmonale, pneumonia, or respiratory failure were placed in one of three groups (men with hypoxia, men without hypoxia, and women). Patients within these groups were then randomly allocated to receive either standard drug treatment alone or standard drug treatment plus intermittent positive-pressure ventilation (IPPV). No significant differences occurred between the controls and patients receiving physiotherapy and IPPV in any group. We conclude that when a patient with chronic bronchitis and respiratory failure is deteriorating emphasis should be on correct diagnosis, fluid electrolyte balance, and nutrition together with oxygen treatment when necessary, rather than on additional physiotherapy.


Interlocking nailing of femoral shaft fractures with an extremely narrow medullary canal is associated with iatrogenic fractures.
Controversy exists regarding the use of reamed interlocking nailing in femoral shafts with extremely narrow medullary canals (diameter ≤ 9 mm). The aims of this study were to (1) investigate the association of age and sex on femoral canal diameter in patients with a simple femoral shaft fracture and (2) compare the outcomes and complications of interlocking nailing between wide and extremely narrow intramedullary canals. For the purposes of this retrospective cohort study, consecutive patients with simple femoral shaft fractures were recruited between January 2009 and December 2016. The patient demographic data were analyzed. Then, fractures treated with interlocking nailing were divided into the wide group (canal diameter > 9 mm) and narrow group. The primary outcome was union rate, and the secondary outcomes were complications such as thermal necrosis, fat embolism syndrome, iatrogenic fracture, and implant failure. This study included 340 femoral shaft fractures. The average canal diameter was 9.97 ± 1.79 mm, with significantly wider canals in men than in women. Overall, 289 of the patients had undergone interlocking nail fixation, and a similar union rate and complications were noted between the wide canal and narrow canal groups, with the exception of the incidence of iatrogenic fracture. Femoral shaft fractures associated with extremely narrow medullary canals are more common in women than in men. There was a similar union rate found when using interlocking nailing in a femoral shaft fracture in cases with extremely narrow and wider canals. Iatrogenic fracture is the only significant risk when using interlocking nailing in femoral shafts with extremely narrow canals.


Protective effects of silymarin against bisphenol A-induced hepatotoxicity in mouse liver.
Bisphenol A (BPA) is an endocrine-disrupting chemical released into the environment, with severe consequences for human health, including metabolic syndrome and associated pathological conditions. Due to limited information on BPA-induced hepatotoxicity, the present study focused on investigating the association between BPA-induced toxicity and inflammatory markers in the liver, and how these injuries may be alleviated using the natural agent silymarin, a flavonoid with antioxidant properties obtained from Silybum marianum. Administration of BPA to male CD-1 mice for 10 days caused a significant increase in the number of cells immunopositive for interleukin 6 and tumor necrosis factor-α, pro-inflammatory cytokines that mediate the hepatic inflammatory response. Treatment with 200 mg/kg of silymarin concurrently with BPA for 10 days resulted in a diminished level of pro-inflammatory cytokines and in significantly reduced ultrastructural injuries. Additionally, silymarin was able to restore the significantly decreased glycogen deposits observed following BPA exposure to normal levels, thus favoring hepatic glycogenesis. This study represents the first report of silymarin ability to reduce hepatic lesions and to counteract inflammation caused by BPA in mice. A dose of 200 mg/kg silymarin was sufficient to induce a protective effect against structural and ultrastructural injuries induced by BPA and to lower the levels of pro-inflammatory cytokines observed in murine liver tissue following exposure to BPA.


A new device used in the restoration of kinematics after total facet arthroplasty.
Facet degeneration can lead to spinal stenosis and instability, and often requires stabilization. Interbody fusion is commonly performed, but it can lead to adjacent-segment disease. Dynamic posterior stabilization was performed using a total facet arthroplasty system. The total facet arthroplasty system was originally intended to restore the natural motion of the posterior stabilizers, but follow-up studies are lacking due to limited clinical use. We studied the first 14 cases (long-term follow-up) treated with this new device in our clinic. All patients were diagnosed with lumbar stenosis due to hypertrophy of the articular facets on one to three levels (maximum). Disk space was of normal height. The design of this implant allows its use only at levels L3-L4 and L4-L5. We implanted nine patients at the L4-L5 level and four patients at level L3-L4. Postoperative follow-up of the patients was obtained for an average of 3.7 years. All patients reported persistent improvement of symptoms, visual analog scale score, and Oswestry Disability Index score. Functional scores and dynamic radiographic imaging demonstrated the functional efficacy of this new implant, which represents an alternative technique and a new approach to dynamic stabilization of the vertebral column after interventions for spine decompression. The total facet arthroplasty system represents a viable option for dynamic posterior stabilization after spinal decompression. For the observed follow-up, it preserved motion without significant complications or apparent intradisk or adjacent-disk degeneration.


Spread of multidrug resistance in non-PCV13/PCV20 serotypes of Streptococcus pneumoniae: A cross-sectional study ten years after the introduction of pneumococcal conjugate vaccine in Japan.
Ten years after the introduction of the pneumococcal conjugate vaccine (PCV) in Japan, the prevalence rates of non-PCV13 and non-PCV20 serotypes among pediatric pneumococcal isolates were 94.0% and 73.7%, respectively. The predominant non-PCV13/PCV20 serotypes (15A, 35B, and 23A) were mostly multidrug-resistant (≥80.5%), exhibiting non-susceptibility to penicillin.


Spine and spinal cord injuries--causes and complications.
The spine as a motor organ is very often exposed to the action of forces released by an injury. The most frequent cause of spine and spinal cord injuries are traumas which are the result of accidents, and untreated osteoporosis or neoplasms as well. Aim of the study is an analysis of the causes of spine and spinal cord injuries as well as of the complications of these injuries. The material covers 130 patients hospitalized due to spine injury in 2008-2010 at the Clinical Department of Neurosurgery of Wroclaw Medical University. The data has been obtained on the basis of an analysis of medical and nursing documentation. In the research group, men (64%) prevail over women (36% of the respondents). Most often, spine injuries affected patients aged over 60. Spine injuries without spinal cord injury comprised 84.6%, whereas with spinal cord injury only 15.4%. About 75% of the examined patients were admitted to the department as emergency admissions, within the time exceeding 12 hours since an injury occurrence (58.5%). The vast majority of patients (80%) were treated surgically. After completing treatment, most of the respondents were discharged (71.5%). After leaving the hospital, over half of the patients (52.3%) were not able to move on their own. The most common causes of spine injuries in patients are pathologic injuries (28.5%), traffic collisions (27.7%) and falls from heights (20.0%). To the largest degrees, spine injuries concerned the thoracic segment (in 34.6%), cervical segment (32.3%) and lumbar (23.8%). Complications occurring after spine injuries included pain of a damaged spine segment (61.1%), pain in other location (36.6%) and gastroenterological complications (17.6%). In the case of complications after spine and spinal cord injuries, gastroenterological complications predominate (in 42.9% patients) along with complications of the urinary system (38.1%) and pain of the injured spine segment (38.1%).


The composition of Australian fur seal (Arctocephalus pusillus doriferus) milk throughout lactation.
The proximate chemical composition of milk was determined throughout lactation in the Australian fur seal (Arctocephalus pusillus doriferus Wood Jones), a temperate species with an 11-mo lactation period typical of most temperate otariids. Average lipid and protein contents were 42% and 10%, respectively, which is similar to that recorded for the polar otariid species but higher than reported in other temperate, long-lactation species. Milk composition, however, varied substantially throughout lactation, with lipid content rising from 30% soon after parturition to 50% at 230 d postpartum before decreasing to 45% toward weaning. The trend in water content was opposite to that of lipid, while protein content increased only slightly during lactation from 10% to 12%. The peak in lipid content occurred at approximately 70% of the way through lactation, similar to that found in the Australian sea lion and several phocid seal species. Significant positive relationships were found between milk lipid content and both the duration of the preceding foraging trip and body mass. A highly significant and close correlation was found between milk water and lipid contents such that gross energy content may be accurately predicted from water content alone. Similar predictive equations have been found for several other otariid and phocid species, but these appear to differ between phylogenetic groups.


Metacognitive Beliefs as Predictors of Return to Work After Intensive Return-to-Work Rehabilitation in Patients With Chronic Pain, Chronic Fatigue and Common Psychological Disorders: Results From a Prospective Trial.
Metacognitions are associated with work status, but no research has examined to what extent metacognitions before treatment and change in metacognitions following treatment predict return to work (RTW) prospectively. The present study aims to address these two gaps in knowledge. 212 patients on long-term sick leave (>8 weeks) with extensive fatigue, chronic pain conditions and/or mental distress received 3.5 weeks of intensive rehabilitation treatment, aimed at returning them to work. Only part of the population (n = 137) had complete follow-up data on metacognitions. Metacognitions were measured with the Metacognitions Questionnaire 30 (MCQ-30), while RTW was measured using official registry data from the Norwegian Labor and Welfare Service. A registry record of participation in competitive work ≥2.5 days (50% work participation) per week, averaging over 14 weeks, was chosen as an outcome reflecting a successful RTW. The registry data spanned a total of 56 weeks per participant. Our results indicated that baseline MCQ scores was not associated with RTW. This was analyzed for the total MCQ score as well as for all subscales. We observed substantial changes in metacognitions following treatment, and a 1-point change in the total sum of metacognitive beliefs was associated with 5% greater odds for successful RTW at all time points (p = 0.040), while a 1-point change on the subscale of beliefs about the need to control thoughts gave 20% greater odds for successful RTW (p = 0.016). Metacognitions concerning the need to control thoughts appear to have a significant influence on patients return to work. Here, we observed that a change in these beliefs following treatment substantially affected RTW over the course of 1 year.


Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study.
Neuregulin-1 proteins are related to physiological correlates of Type A in terms of cardiac reactivity. Furthermore, neuregulin-1 gene (NRG1) may play a role in cardiovascular disease such as atherosclerosis and coronary heart disease i.e. the suggested "outcomes" of Type A behavior. Therefore, NRG1 is hypothesized to be associated with Type A behavior. The study examined whether Type A behavior pattern is associated with the single nucleotide polymorphism (SNP) SNP8NRG221533 of the NRG1. The subjects were 631 men and women participating in the population-based Cardiovascular Risk in Young Finns study in 1992 and 2001. Type A was self-assessed with the Framingham Type A Scale and reassessed nine years later. Type A was associated with NRG1 genotype. Carriers of genotype CC scored lower on Type A compared to the others. Our study has pinpointed a SNP in NRG1 that predicts Type A behavior. As previous evidence suggests an association for NRG1 with beta-adrenergic stimulation, its role underlying Type A is discussed.


Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model.
We analyzed the inheritance of body fat, leptin levels, plasma lipoprotein levels, insulin levels, and related traits in an intercross between inbred mouse strains CAST/Ei and C57BL/6J. CAST/Ei mice are unusually lean, with only approximately 8% of body weight as fat, whereas C57BL/6J mice have approximately 18% body fat. Quantitative trait locus analysis using > 200 F2 mice revealed highly significant loci (lod scores > 4.3) on chromosomes 2 (three separate loci) and 9 that contribute to mouse fat-pad mass for mice on a high-fat diet. Some loci also influenced plasma lipoprotein levels and insulin levels either on chow or high-fat diets. Two loci for body fat and lipoprotein levels (on central and distal chromosome 2) coincided with a locus having strong effects on hepatic lipase activity, an activity associated with visceral obesity and lipoprotein levels in humans. A locus contributing to plasma leptin levels (lod score 5.3) but not obesity was identified on chromosome 4, near the leptin receptor gene. These data identify candidate regions and candidate genes for studies of human obesity and diabetes, and suggest obesity is highly complex in terms of the number of genetic factors involved. Finally, they support the existence of specific genetic interactions between body fat, insulin metabolism, and lipoprotein metabolism.


Rethinking revenue collection at military MTFs (medical treatment facilities).
Military medical treatment facilities (MTFs) throughout the nation have felt the impact of the dramatic transition from traditional fee-for-service health insurance coverage to managed care programs. Some facilities have had to struggle to survive. Yet one facility, the Naval Medical Center-San Diego, San Diego, California, nearly doubled its revenue collections in spite of a reduction in billable claims, reduced staff, and a substantial increase in non-billable policies.


Observer variability of tibial plateau slope measurement in 40 dogs with cranial cruciate ligament-deficient stifle joints.
To determine (1) the inter- and intraobserver variability in measurement of tibial plateau angle (TPA), (2) whether this inter- and intraobserver variability is related to the characteristics of the dog (age, size, and amount of degenerative joint disease [DJD]) and the experience level of the observer, and (3) the extent of any relationship between interobserver variability of TPA and the variability of the observers' selection of the specific cranial and caudal points along the tibial plateau. Examination of tibial radiographs of 40 dogs clinically affected with a cranial cruciate ligament (CrCL)-deficient stifle joint. Eleven different observers, divided into 3 groups based on their level of experience with the tibial plateau leveling osteotomy (TPLO) technique, measured the TPA on all 40 radiographs on 5 different occasions. The degree of DJD present in the stifle joint was independently graded as an overall measure and then again as it specifically related to the cranial and caudal points along the tibial plateau. The total observed variabilities of the TPA were assessed with reference to interobserver differences, intraobserver differences, and among the groups of observers with respect to the different dog characteristics. Finally, the specific points selected on the radiographs were reexamined to determine whether any variability was present in cranial and caudal point selection. The interobserver standard deviation of the TPA measurements for each dog was 0.8 degrees, and the intraobserver standard deviation was 1.5 degrees. The TPA measurements obtained by the 11 observers differed significantly from each other (P <.001); however, there was no significant difference of TPA among the different groups of observers (P =.67). There was no significant correlation observed between either the inter- or intraobserver variability and the dog characteristics. Specific point data and their relationship to the various variables of dog characteristics and inter- and intraobserver TPA variability revealed significant correlations only to the amount of DJD present at the caudal point (P =.001). Interobserver variation, but no significant group variation, was present. Overall DJD did not appear to be related to the variability in TPA angle measurement. Most of the interobserver variability was attributable to variability in horizontal point selection at both the cranial and caudal points and vertical point selection at the caudal point. It appears that degenerative changes that specifically obscure the points on the tibial plateau, especially at the caudal point, are responsible for most of the interobserver variation. The desired postoperative TPA of 5 degrees is dependent on a precise initial measure of TPA preoperatively. This study indicates that there is statistically significant interobserver variability with measurement of TPA, which, therefore, can result in a similar amount of variability with the final tibial plateau slope obtained postoperatively.


Effect of Temporal Changes in Air Injection Rate on Air Sparging Performance Groundwater Remediation.
Air sparging (AS) is a commonly applied method for treating groundwater contaminated with volatile organic compounds (VOCs). When using a constant injection of air (continuous mode), a decline in remediation efficiency is often observed, resulting from insufficient mixing of contaminants at the pore scale. It is well known that turning the injection on and off (pulsed mode) may lead to a better remediation performance. In this article, we investigate groundwater mixing and contaminant removal efficiency in different injection modes (i.e., continuous and pulsed), and compare them to those achieved in a third mode, which we denote as "rate changing." In this mode, injection is always on, and its rate is varying with time by abrupt changes. For the purpose of this investigation, we conducted two separate sets of experiments in a laboratory tank. In the first set of experiments, we used dye plume tracing to characterize the mixing induced by AS. In the second set of experiments, we contaminated the tank with a VOC and compared the remediation efficiency between the different injection modes. As expected, we observed that time-variable injection modes led to enhanced mixing and contaminant removal. The decrease in contaminant concentrations during the experiment was found to be double for the "rate changing" and "pulsed" modes compared to the continuous mode, with a slightly preferable performance for the "rate changing" mode. These results highlight the critical role that mixing plays in AS, and support the need for further investigation of the proposed "rate changing" injection mode.


[Study of the irreversible conformation change of immunoglobulin M by spin-labeling at the carbohydrate and peptide moieties of the molecule].
The irreversible conformational change of the immunoglobulin M (IgM) molecule (Waldenström disease) at pH approximately 3 was studied by means of spin-labels introduced in the carbohydrate (2,2,6,6,-tetramethyl-4-aminopiperidine-1-oxyl) and peptide (2,2,5,5,-tetramethyl-3-(dichloro-symm.-triazinylamino)-pyrrolidine-1-oxyl) moieties of the molecule. A marked rise of structure density of IgM especially in the (Fc)5-region and some minor local conformational changes in the Fab-regions were found. Comparison of our findings with the published data shows that Fab-regions of the principal immunoglobulins are rigid structures. Steric hindrance for Fab-regions increases markedly in the row Fab--F(ab')2--IgG--IgA--IgM restricting their spatial mobility. Monomeric Fc-regions of IgM are evidently flexible and one of the domains is especially mobile. It is supposed that oligosaccharide groups of IgM are of two types which differ in their spatial mobility. It was found by ammonium sulfate precipitation of IgM spin-labeled at the peptide moiety that the relative mobility of amino acid residues coupled with spin-label is strongly restricted.


Chemical, biochemical and cellular responses in the digestive gland of the mussel Mytilus galloprovincialis from the Spanish Mediterranean coast.
Mussels (Mytilus galloprovincialis) were sampled in March 1996 from five stations along the Western Mediterranean coast (Barcelona, Ebro Delta, Alboraya, Cullera, Denia) corresponding to urban, industrial and agricultural areas. Different biochemical and cellular markers were determined in the mussels in order to assess the effects and/or exposure to pollutants. The cytochrome P450 system, acetylcholinesterase and metallothioneins were among the biochemical markers selected for the study. Histochemical analysis of ß-glucuronidase and catalase activity were performed as marker enzymes for lysosomes and peroxisomes. Chemical analyses indicated that mussels from Barcelona and Denia as highly exposed to polycyclic aromatic hydrocarbons (PAHs)(1.8-2.7 µg g(-1) w.w. against 0.02-0.10 µg g(-1) w.w.), and polychlorinated biphenyls (PCBs)(132-260 ng g(-1) w.w. against 8-24 ng g(-1) w.w.). This was in agreement with changes in lysosome structure and higher number of peroxisomes in those organisms. High levels of metals (particularly Cr and Cu) were recorded in the digestive gland of Alboraya mussels, which also had elevated metallothionein content (28 nmol g(-1) w.w.) in comparison with the other stations (15-20 nmol g(-1) w.w.). Benzo(a)pyrene hydroxylase (BPH) activity indicated Cullera and Barcelona as possibly polluted sites. The results support the usefulness of the biomarker approach to assess and diagnose environmental pollution. The use of a battery of biomarkers at different levels of biological organization coupled with chemical analysis is highlighted.


MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.
Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.


Fine mapping of a distal chromosome 4 QTL affecting growth and muscle mass in a chicken advanced intercross line.
In our previous research, QTL analysis in an F2 cross between the inbred New Hampshire (NHI) and White Leghorn (WL77) lines revealed a growth QTL in the distal part of chromosome 4. To physically reduce the chromosomal interval and the number of potential candidate genes, we performed fine mapping using individuals of generations F10 , F11 and F12 in an advanced intercross line that had been established from the initial F2 mapping population. Using nine single nucleotide polymorphism (SNP) markers within the QTL region for an association analysis with several growth traits from hatch to 20 weeks and body composition traits at 20 weeks, we could reduce the confidence interval from 26.9 to 3.4 Mb. Within the fine mapped region, markers rs14490774, rs314961352 and rs318175270 were in full linkage disequilibrium (D' = 1.0) and showed the strongest effect on growth and muscle mass (LOD ≥ 4.00). This reduced region contains 30 genes, compared to 292 genes in the original region. Chicken 60 K and 600 K SNP chips combined with DNA sequencing of the parental lines were used to call mutations in the reduced region. In the narrowed-down region, 489 sequence variants were detected between NHI and WL77. The most deleterious variants are a missense variant in ADGRA3 (SIFT = 0.02) and a frameshift deletion in the functional unknown gene ENSGALG00000014401 in NHI chicken. In addition, five synonymous variants were discovered in genes PPARGC1A, ADGRA3, PACRGL, SLIT2 and FAM184B. In our study, the confidence interval and the number of potential genes could be reduced 8- and 10- fold respectively. Further research will focus on functional effects of mutant genes.


Comparison of the performance of MBBR and SBR systems for the treatment of anaerobic reactor biowaste effluent.
Anaerobic reactor biowaste effluent was treated with biofilm and activated sludge sequencing batch reactors to compare the performance of both systems. The treatment targets were organic carbon removal and nitrification. The pilot plant was operated in two phases. During the first phase, it was operated like a Moving Bed Biofilm Reactor (MBBR) with the Natrix media, with a specific surface area of 210 m2/m3. The MBBR was operated under Sequencing Batch Reactor (SBR) modality with three 8-hour cycles per day over 70 days. During the second phase of the experiment, the pilot plant was operated over 79 days as a SBR. In both phases the influent was fed to the reactor at a flow rate corresponding to a Hydraulic Retention Time (HRT) of 4 days. Both systems presented a good carbon removal for this specific wastewater. The Chemical Oxygen Demand (COD) total removal was 53% for MBBR and 55% for SBR. MBBR offered a higher dissolved COD removal (40%) than SBR (30%). The limited COD removal achieved is in agreement with the high COD to BOD5 ratio (1/3) of the influent wastewater. In both systems a complete nitrification was obtained. The different efficiencies in both systems are related to the different biomass concentrations.


Evolution of blood coagulation activators and inhibitors in the healthy human fetus.
Blood coagulation proteins were determined in 285 healthy fetuses from 19 to 38 weeks' gestation and compared with those of 60 normal full-term newborns and 40 adult controls. Prolongation of the coagulation screening tests, prothrombin time, activated partial prothrombin time, and thrombin clotting time, in fetuses throughout intrauterine life was explained by low levels of vitamin K-dependent factors (II, VII, IX, and X), contact factors (XI, XII, prekallikrein, and high-molecular-weight kininogen), factor V, factor VIII, and fibrinogen. Low levels of antithrombin III, heparin cofactor II, protein C and protein S, and tissue factor pathway inhibitor were also found, and these probably contributed to a satisfactory hemostatic balance. Some of these parameters were evaluated by both immunologic and functional assays to detect possible "fetal" proteins. An increase in factor levels was observed after the thirty-fourth week of intrauterine life for most of the coagulation activators and inhibitors, but only factors V and VIII reached adult values at birth. This study therefore showed that fetal hemostasis is a dynamic system that evolves gradually toward the neonatal state and then toward the adult state.


Specific receptors for the serum thymic factor (FTS) in lymphoblastoid cultured cell lines.
The interaction of the synthetic serum thymic factor (FTS, "facteur thymique sérique") with human T lymphocytes from two established T cell lines (1301 and HSB2) was studied by using [3H]FTS. At 30 degrees C, in the presence of 10 nM labeled FTS, a steady state was observed within 120 min. Bound labeled FTS was dissociated by simultaneous addition of an excess of unlabeled FTS (dissociation constant Kd = 3 nM). The binding of [3H]FTS was reduced to 10-20% when unlabeled FTS was added at 20 microgram/ml (20 micro M), but not when unrelated peptides or FTS analogues differing from FTS by only one amino acid residue were added. No FTS binding was detectable on B and null cell lines or on two T cell lines other than 1301 and HSB2. These data indicate that only certain T cell subsets possess receptors with high affinity and specificity for FTS.


Polypeptides specified by bacteriophage T1.
The proteins synthesized during the replication of phage TI in u.v.-irradiated Escherichia coli strain B have been examined by polyacrylamide gel electrophoresis of polypeptides pulse-labelled with 14C-amino acids. Up to 50 discrete bands were identified of which about 30 were sufficiently distinct to be classified in terms of time of synthesis. Three polypeptides were synthesized only during the first 6 to 8 min post infection (Class I, Early); 16 or 17 were synthesized predominantly during the later stages of replication starting from 6 to 8 min after infection (Class III, Late); three classes of proteins were made continuously, two at constant rate (Class II, Continuous), five at decreasing rate (Class IV, Early-continuous) and five at increasing rate (Class V, Late-continuous). Of the 14 polypeptides identified as structural components of the virion, three (P7, PI0 and PI) account for about 85% of the particle weight with P7 comprising 50% of the particle. P7 and PI0 appear to result from the cleavage of larger polypeptides. Preliminary studies with amber mutants suggest that normal levels of TI DNA synthesis are not required for the manufacture of late proteins and that a phage-controlled function may control the switch-off of proteins made early and the switch-on of proteins made late.


Transient Batteries: A Promising Step Towards Powering Green Electronics.
Transient electronics is an emerging class of innovative technology wherein electronic devices undergo controlled degradation processes after a period of stable operation, leaving no toxic products behind. This technology offers exciting opportunities in research areas of green electronics, temporary biomedical implants, data-secure hardware systems, and many others. However, one major challenge with these devices is their rigid and bulky batteries that contain toxic chemicals and are not at all degradable. So, to realize autonomous and self-sufficient transient electronics, the development of transient batteries is a pre-requisite. This review provides an overview of the advancements in the field of transient batteries, their materials, output performance, transience behaviour, and a few potential applications.


Gliomas in rodent whisker barrel cortex: a new tumor model.
Surgical treatment of gliomas is difficult because they are invasive. Invasion of essential cortex often limits or precludes surgical resection. A tumor model was developed in which the rodent whisker barrel cortex was used to examine how gliomas affect cortical function and structure. Both DBT (mouse) and C6 (rat) glioma cell lines were grown in culture and labeled with the fluorescent marker Dil in vitro. Labeled tumor cells were then injected into the whisker barrel cortex of adult mice and rats. Neurological assessments were made daily and magnetic resonance (MR) images were obtained. Animals were killed by perfusion 6 to 14 days after injection, and histological sections were prepared and studied. Tumors were found in all 20 rats and 10 mice that had been injected with the C6 and DBT cell lines, respectively. The animal cells had been labeled with Dil in vitro, and all in vivo tumors proved to be Dil positive. The MR images revealed the tumor locations and serial MR images demonstrated tumor growth. Histological evaluation confirmed the location of the tumor and the disruption of barrel cortex architecture. Both DBT and C6 glioma cell lines can be used to generate malignant glial tumors reproducibly in the whisker barrel cortex. Fluorescent labeling and cytochrome oxidase staining permit visualization of tumor growth patterns, which disrupt the barrel cortex by microscopic invasion and by gross tissue deformation. Magnetic resonance imaging demonstrates the anatomical extension of these tumors in live rodents. Using this model for further studies on the effects of malignant glioma growth on functional cerebral cortex should advance our understanding of the neurological issues and management of patients with these tumors.


High expression of TREM2 promotes EMT via the PI3K/AKT pathway in gastric cancer: bioinformatics analysis and experimental verification.
Background: To date, the pathogenesis of gastric cancer (GC) remains unclear. We combined public database resources and bioinformatics analysis methods, explored some novel genes and verified the experiments to further understand the pathogenesis of GC and to provide a promising target for anti-tumor therapy. Methods: We downloaded the chip data related to GC from the Gene Expression Omnibus (GEO) database, extracted differentially expressed genes (DEGs), and then determined the key genes in the development of GC via PPI networks and model analysis. Functional annotation via GO and KEGG enrichment of DEGs was used to understand the latent roles of DEGs. The expression of the triggering receptor expressed on myeloid cells 2 (TREM2) gene in GC cell lines was verified via RT-PCR and western blotting. Moreover, the CCK-8, wound healing assay, and transwell migration and invasion assays were used to understand the changes in the proliferation, migration, and invasion abilities of GC cells after silencing TREM2. Western blotting verified the interaction between TREM2 and PI3K predict of the string website, as well as the effect of TREM2 on EMT. Finally, a lung metastasis model was used to explore the relationship between TREM2 and metastasis. Results: Our study identified 16 key genes, namely BGN, COL1A1, COL4A1, COL5A2, NOX4, SPARC, HEYL, SPP1, TIMP1, CTHRC1, TREM2, SFRP4, FBXO32, GPX3, KIF4A, and MMP9 genes associated with GC. The EMT-related pathway was the most significantly altered pathway. TREM2 expression was higher in GC cell lines and was remarkably associated with tumor invasion depth, TNM stage, histological grade, histological type, anatomic subdivision, and Helicobacter pylori state. Knockdown of TREM2 expression inhibited the proliferation, migration, and invasion of GC cells as well as the progression of EMT by PI3K/AKT signaling in vitro. In addition, lung metastasis were decreased in vivo. Conclusions: We identified some important genes associated with the progression of GC via public database analysis, explored and verified the effects of proto-oncogene TREM2 on EMT via the PI3K/AKT pathway. TREM2 may be a novel target in the GC therapy.


Comparison of two yeast MnSODs: mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans.
Human MnSOD is significantly more product-inhibited than bacterial MnSODs at high concentrations of superoxide (O(2)(-)). This behavior limits the amount of H(2)O(2) produced at high [O(2)(-)]; its desirability can be explained by the multiple roles of H(2)O(2) in mammalian cells, particularly its role in signaling. To investigate the mechanism of product inhibition in MnSOD, two yeast MnSODs, one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), were isolated and characterized. ScMnSOD and CaMnSODc are similar in catalytic kinetics, spectroscopy, and redox chemistry, and they both rest predominantly in the reduced state (unlike most other MnSODs). At high [O(2)(-)], the dismutation efficiencies of the yeast MnSODs surpass those of human and bacterial MnSODs, due to very low level of product inhibition. Optical and parallel-mode electron paramagnetic resonance (EPR) spectra suggest the presence of two Mn(3+) species in yeast Mn(3+)SODs, including the well-characterized 5-coordinate Mn(3+) species and a 6-coordinate L-Mn(3+) species with hydroxide as the putative sixth ligand (L). The first and second coordination spheres of ScMnSOD are more similar to bacterial than to human MnSOD. Gln154, an H-bond donor to the Mn-coordinated solvent molecule, is slightly further away from Mn in yeast MnSODs, which may result in their unusual resting state. Mechanistically, the high efficiency of yeast MnSODs could be ascribed to putative translocation of an outer-sphere solvent molecule, which could destabilize the inhibited complex and enhance proton transfer from protein to peroxide. Our studies on yeast MnSODs indicate the unique nature of human MnSOD in that it predominantly undergoes the inhibited pathway at high [O(2)(-)].


On the interactions between nucleotide binding domains and membrane spanning domains in cystic fibrosis transmembrane regulator: A molecular dynamic study.
The Cystic Fibrosis Transmembrane Regulator (CFTR) is a membrane protein whose mutations cause cystic fibrosis, a lethal genetic disease. We performed a molecular dynamic (MD) study of the properties of the nucleotide binding domains (NBD) whose conformational changes, upon ATP binding, are the direct responsible of the gating mechanisms of CFTR. This study was done for the wild type (WT) CFTR and for the two most common mutations, ΔF508, that produces a traffic defect of the protein, and the mutation G551D, that causes a gating defect on CFTR. Using an homology model of the open channel conformation of the CFTR we thus introduced the mutations to the structure. Although the overall structures of the G551D and ΔF508 are quite well conserved, the NBD1-NBD2 interactions are severely modified in both mutants. NBD1 and NBD2 are indeed destabilized with a higher internal energy (Ei) in the ΔF508-CFTR. Differently, Ei does not change in the NBDs of G551D but, while the number of close contacts between NBD1 and NBD2 in ΔF508 is increased, a significant reduction of close contacts is found in the G551D mutated form. Hydrogen bonds formation between NBDs of the two mutated forms is also altered and it is slightly increased for the ΔF508, while are severely reduced in G551D. A consequent modification of the NBDs-ICLs interactions between residues involved in the transduction of the ATP binding and the channel gating is also registered. Indeed, while a major interaction is noticed between NBDs interface and ICL2 and ICL4 in the WT, this interaction is somehow altered in both mutated forms plausibly with effect on channel gating. Thus, single point mutations of the CFTR protein can reasonably results in channel gating defects due to alteration of the interaction mechanisms between the NBDs and NBDs-ICLs interfaces upon ATP-binding process.


Impaired VLDL assembly: a novel mechanism contributing to hepatic lipid accumulation following ovariectomy and high-fat/high-cholesterol diets?
The aim of the present study was to identify molecular mechanisms involved in liver fat and cholesterol accumulation in ovariectomised (Ovx) rats fed with high-cholesterol diets. VLDL assembly and bile acid metabolism were specifically targeted. After being either Ovx or sham-operated, the rats were fed a standard diet or a high-fat diet containing 0, 0·25 or 0·5 % cholesterol for 6 weeks. Although Ovx rats exposed to dietary cholesterol intake accumulated the greatest amount of hepatic fat and cholesterol, plasma cholesterol levels were lower (P< 0·05) in these animals than in the corresponding control rats. Accompanying this observation, ovariectomy and dietary cholesterol intake resulted in a down-regulation (P< 0·05) of the expression of genes associated with VLDL assembly, including microsomal TAG transfer protein, diacylglycerol acyltransferase 2, acyl-CoA:cholesterol acyltransferase 2 and apoB-100 as well as genes associated with bile acid metabolism including farnesoid X receptor and bile salt export pump (P< 0·01). These results indicate that high-fat/high-cholesterol diets and ovariectomy concomitantly disrupt hepatic lipid output through defects in VLDL assembly and, most probably, secretion. The results also point to a defect in hepatic bile acid secretion. The present study offers novel insights into intrahepatic lipid metabolism, which may be relevant to metabolic complications found in postmenopausal women.


Increased anxiety-like behavior but no cognitive impairments in adult rats exposed to constant light conditions during perinatal development.
Shift-work is suggested to affect fetal development negatively. In particular, maternal hormonal disturbance arising from sleep deprivation or circadian rhythm changes may disturb fetal growth or lead to complications during pregnancy. Exposure to constant light is an environmental stressor that can affect the circadian system and has been shown to induce neurochemical and behavioral changes when used during the prenatal and/or postnatal period in experimental animals. However, studies investigating long-term effects of constant light in the offspring are sparse. An accidental power outage resulted in pregnant females being housed under constant light (LL) conditions for seven days of the offspring perinatal development (embryonic day 20 to postnatal day 4). The long-term effects of constant light on the behavior in the adult offspring were assessed by means of open field, object recognition, and water maze tests. In adulthood, LL-animals displayed an intact recognition memory and no deficits in spatial learning or memory. In the open field test, LL-animals exhibited higher anxiety-like behavior, observed as significantly more thigmotaxis and less ambulation. These results were confirmed in the other behavioral tests as the LL-animals spent less time exploring the objects in the object recognition test, and showed thigmotactic behavior also in the water maze test. The results confirm that early life experience can cause changes in brain development that shape brain function and add to the sparse literature on long-term effects of constant light conditions during perinatal development on specific behaviors in adulthood.