[Pathognomonic magnetic resonance imaging (MRI) finding of fluid-fluid level in pyogenic ventriculitis: two case reports].
Pyogenic ventriculitis is an uncommon and potentially fatal central nervous system infection. Delayed treatment due to non specific clinical symptoms may lead to an unfavorable outcome. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of pyogenic ventriculitis. We describe two patients with pyogenic ventriculitis presenting with a pathognomonic MRI finding. The first patient, a 77-year-old female, developed high fever and consciousness disturbance. MR images revealed hyperintense lesions with a fluid-fluid level in the bilateral lateral ventricles on diffusion-weighted images (DWIs) and hypointense lesions on T2-weighted images (T2WIs). MR images also revealed findings of left otitis media. The second patient, a 63-year-old male, who had a past history of multiple myeloma and had received chemotherapy, developed high fever and left hemiparesis. MR images revealed a hyperintense lesion with a fluid-fluid level in the right lateral ventricle on DWIs and a hypointense lesion on T2WIs, multiple ring-enhancing lesions on gadolinium enhanced T1-weighted images, and pontine infarction on DWIs. Chest computed tomography revealed an infiltrative shadow in the lower lobe of the left lung. On the basis of MRI findings, both patients were diagnosed as having pyogenic ventriculitis and were administered high-dose meropenem intravenously. The second patient was also administered sulfamethoxazole-trimethoprim orally. Intraventricular abnormalities disappeared and the patients achieved complete remission after the antibacterial treatment. Intraventricular hyperintense lesions on DWIs and hypointense ones on T2WIs with a fluid-fluid level is a pathognomonic finding of pyogenic ventriculitis and has not been previously reported in other diseases. Recognition of the characteristic MRI features and initiation of high-dose and appropriate antibiotics in an early stage may lead to a favorable outcome of the disease.


Arthroscopic-assisted latissimus dorsi tendon transfer for irreparable posterosuperior cuff tears.
To evaluate, in a multicenter, prospective study, the clinical, magnetic resonance imaging (MRI), and radiologic results of arthroscopic-assisted latissimus dorsi (LD) tendon transfer for irreparable posterosuperior rotator cuff tears; and to assess the influence of perioperative data on clinical results. Fifty-five patients with irreparable tears of at least the supraspinatus and infraspinatus tendons were managed with arthroscopic-assisted LD tendon transfer and reviewed clinically, with standardized radiographs and MRI, after a mean of 29 months. Outcome measures included the Constant score and the Subjective Shoulder Value. The osteoarthritic stage and acromiohumeral distance were measured on standardized radiographs, and the transferred tendon aspect was evaluated on MRI. Thirty patients had already undergone 1 or more previous surgical procedures. The mean Subjective Shoulder Value increased from 26% preoperatively to 71% postoperatively. The Constant score improved from 37 preoperatively to 65.4 postoperatively. The pain score increased from 1.7 preoperatively to 12.6 postoperatively; the activity score, from 6.4 to 13.8; active forward flexion, from 134° to 157°; active abduction, from 67° to 92.5°; active external rotation, from 29° to 41.5°; and abduction strength, from 1.4 kg to 4.8 kg. The only statistically significant factor negatively influencing the Constant score was previous surgery. Four patients had a ruptured LD tendon on MRI follow-up at 1 year. There was no statistical difference between preoperative and final follow-up acromiohumeral distance. There was no increase in osteoarthritic stage. Arthroscopic-assisted LD tendon transfer improves shoulder pain and function in patients with irreparable posterosuperior cuff tears, with similar clinical and radiologic results compared with results of published series using open techniques. Patients with a history of surgery had lower Constant scores compared with non-previously operated patients. Level IV, therapeutic case series.


Phospho-kinase profile of colorectal tumors guides in the selection of multi-kinase inhibitors.
Protein kinases play a central role in the oncogenesis of colorectal tumors and are attractive druggable targets. Detection of activated kinases within a tumor could open avenues for drug selection and optimization of new kinase inhibitors. By using a phosphokinase arrays with human colorectal tumors we identified activated kinases, including the Epidermal Growth Factor Receptor (EGFR), components of the PI3K/mTOR pathway (AKT and S6), and STAT, among others. A pharmacological screening with kinase inhibitors against these proteins helped us to identify a new kinase inhibitor, termed EC-70124 that showed the highest anti-proliferative activity in cell lines. EC-70124 also inhibited cell migration and biochemical experiments demonstrated its effect targeting the PI3K/mTOR pathway. This drug also arrested cells at G2/M and induced apoptosis. Experiments in combination with standard chemotherapy used in the clinical setting indicated a synergistic effect. EC-70124 also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by studying the kinase profile of colorectal tumors, we identified relevant activated pathways, and a new multi-kinase compound with significant antitumor properties.


Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference.
The question of whether long-term chronic exposure to microplastics (MPs) could induce dose- and size-dependent adverse effects in mammals remains controversial and poorly understood. Our study explored potential health risks from dietary exposure to environmentally relevant doses of polystyrene (PS) MPs, through a mouse model and integrated analyses of the interruptions of fecal microbial metagenomes and plasma lipidomes. After 21 weeks of exposure to the MPs (40-100 μm), mice mainly exhibited gut microbiota dysbiosis, tissue inflammation, and plasma lipid metabolism disorder, although no notable accumulation of MPs was observed in the gut or liver. The change of the relative abundance of microbiota was strongly associated with the exposure dose and size of MPs while less significant effects were observed in gut damage and abnormal lipid metabolism. Moreover, multiomics data suggested that the host abnormal lipid metabolism was closely related to bowel function disruptions, including gut microbiota dysbiosis, increased gut permeability, and inflammation induced by MPs. We revealed for the first time that even without notable accumulation in mouse tissues, long-term exposure to MPs at environmentally relevant doses could still induce widespread health risks. This raises concern on the health risks from the exposure of humans and other mammals to environmentally relevant dose MPs.


Characterization of the aroma of a meatlike process flavoring from soybean-based enzyme-hydrolyzed vegetable protein.
Defatted soybean meal was converted into enzyme-hydrolyzed vegetable protein (E-HVP) using the proteolytic enzyme Flavorzyme. Total free amino acids increased by 40-fold after enzyme hydrolysis, with leucine being the most abundant, followed by phenylalanine, lysine, glutamine/glutamic acid, and alanine. Volatile components from a meatlike process flavoring made from E-HVP were isolated by direct solvent extraction (DSE)-high vacuum transfer (HVT), dynamic headspace sampling and static headspace sampling and analyzed by gas chromatography (GC)-mass spectrometry and GC-olfactometry. Aroma extract dilution analysis was used to establish a flavor dilution chromatogram of the DSE-HVT extract. Results of these complementary techniques indicated the importance of odorants of high (hydrogen sulfide and methanethiol), intermediate (2-methyl-3-furanthiol, 3-mercapto-2-pentanone, 2-furanmethanethiol, and 3-(methylthiol)propanal) and low volatility (maltol and Furaneol) in the overall aroma of the meatlike process flavoring.


Splay-bend periodic deformation in nematic liquid crystal slabs.
We predict a two-dimensional splay-bend periodic deformation in a nematic slab with homeotropic boundary conditions. The nematic director modulation is induced by surface contributions in the elastic energy, which are linear in the deformation tensor. The instability appears only if the surface anchoring energy strength is small enough, and if the two surfaces are different. The wave vector of the stripe modulation is proportional to the thickness of the nematic slab. The order of magnitude of the surface elastic constants relevant to the linear elastic terms in the deformation tensor, and the critical value of the anchoring energy, greater than or approximately 10(-6) J/m(2), to observe the instability are discussed.


The management strategies of cancer-associated anorexia: a critical appraisal of systematic reviews.
Cancer-related anorexia remains one of the most prevalent and troublesome clinical problems experienced by patients with cancer during and after therapy. To ensure high-quality care, systematic reviews (SRs) are seen as the best guide. Considering the methodology quality of SRs varies, we undertook a comprehensive overview, and critical appraisal of pertinent SRs. Eight databases (between the inception of each database and September 1, 2017) were searched for SRs on the management of cancer-related anorexia. Two researchers evaluated the methodological quality of each SR by using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. Characteristics of the "high quality" SRs were abstracted, included information on relevant studies numbers, study design, population, intervention, control, outcome and result. Eighteen SRs met the inclusion criteria. The R-AMSTAR scores of methodological quality ranged from 18 to 41 out of 44, with an average score of 30. Totally eight SRs scored ≥31 points, which showed high methodological quality, and would be used for data extraction to make summaries. Anamorelin had some positive effects to relieve cancer anorexia-cachexia syndrome (CACS) and improve the quality of life (QoL). Megestrol Acetate (MA) could improve appetite, and was associated with slight weight gain for CACS. Oral nutritional interventions were effective in increasing nutritional intake and improving some aspects of QoL in patients with cancer who were malnourished or at nutritional risk. The use of thalidomide, Eicosapentaenoic Acid, and minerals, vitamins, proteins, or other supplements for the treatment of cachexia in cancer were uncertain, and there was inadequate evidence to recommend it to clinical practices, the same situation in Chinese Herb Medicine and acupuncture (acupuncture and related therapies were effective in improving QoL) for treating anorexia in cancer patients, warranting further RCTs in these areas. Anamorelin, MA, oral nutrition interventions, and acupuncture could be considered to be applied in patients with cancer-related anorexia. Future RCTs and SRs with high quality on the pharmaceutical or non-pharmaceutical interventions of anorexia in cancer patients are warranted.


Attitudes toward psychotropic medications.
Attitudes and beliefs towards psychotropic medication were evaluated among psychiatric outpatients, patients receiving buprenorphine treatment for substance abuse, and a group who reported never having used psychotropic medications (non-users). The Drug Attitude Inventory scale and the Beliefs about Medicines Questionnaire General were used to assess attitudes and beliefs of 49 participants. Non-users exhibited more negative attitudes and beliefs toward psychotropic medication than both psychiatric groups.


Landslides, risk and decision-making in Kinnaur District: bridging the gap between science and public opinion.
In November 1989 a major landslide destroyed the link road to the village of Sapni in Kinnaur District of Himachal Pradesh in the Indian Himalaya. Although aware of the risk of further landslide activity, the community has campaigned successfully for reconstruction of the road. Decisions of this kind take place at the local level, through village institutions and open debate, with good feedback between villages and district government authorities. In this way a balance is established between meeting more immediate needs (such as domestic water supply, irrigation, road access) and taking acceptable risks. Using the Sapni landslide as a case study, this paper explores the issue of 'acceptable risk', and looks at the existing strategy for risk and disaster reduction in the district.


Abuse and toxicity of methylphenidate.
The therapeutic use of methylphenidate for the management of attention-deficit hyperactivity disorder in children is increasing. As therapeutic use increases, the risk increases of unintentional overdoses, medication errors, and intentional overdoses caused by abuse, misuse, or suicide gestures and attempts. Side effects during therapy, which include nervousness, headache, insomnia, anorexia, and tachycardia, increase linearly with dose. Clinical manifestations of overdoses include agitation, hallucinations, psychosis, lethargy, seizures, tachycardia, dysrhythmias, hypertension, and hyperthermia. Methylphenidate tablets can be abused orally, or they can be crushed and the powder injected or snorted. Despite its abuse potential, there is disagreement regarding the extent to which methylphenidate is being diverted from legitimate use to abuse in preteens and adolescents.


p53 protein expression in patients with myelodysplasia treated with allogeneic bone marrow transplantation.
Tumor protein 53 mutations adversely affect the prognosis of myelodysplastic syndromes (MDS); however, few studies have reported on the prognostic significance of the expression of p53 protein in MDS. The current study investigated p53 immunoreactivity (p53-IR) in bone marrow biopsies (BMBs) obtained at diagnosis from 18 patients (6 females and 12 males; mean age, 50.5 years) with MDS that underwent bone marrow transplantation (BMT) to determine the associations between clinical and histopathological data and outcome. There were 5 refractory cytopenia with multilineage dysplasia (RCMD) and 13 refractory anemia with excess blasts, type 2 (RAEB-2) cases. p53-IR was assessed as the percentage of hematopoietic cells exhibiting intense nuclear staining. The cut off for positivity was 5% of stained cells. A positive p53-IR was detected in 7 patients (38.9%) and was associated with age (P=0.005) and pattern of BM fibrosis (P=0.03). A positive p53-IR was more frequent in females, in highly cellular BMBs and in RAEB-2 cases. Overall survival (OS) was associated with patients' age (P=0.01), hemoglobin level (P=0.04), type of MDS (P=0.05), degree of BM fibrosis (P=0.006) and number of BM blasts (P=0.05). The OS of patients with negative p53-IR tended to be longer compared with that of patients with positive p53-IR, although this difference was not statistically significant (P=0.1). Despite the limitation of the low number of cases, the present results indicate that a positive p53-IR at diagnosis is associated with clinically more aggressive MDS subtypes and adverse histological prognostic factors, such as BM fibrosis. Therefore, the evaluation of p53 expression of BMBs of patients with MDS may be introduced in the histopathological work-up of the disease.


Fissarcturus walteri sp. nov. from the Ross Sea of the Southern Ocean (Isopoda, Antarcturidae).
During the Victoria-Land Transect project two specimens of a new species, Fissarcturus walteri sp. nov., were found in the Ross Sea along the Victoria Land Coast, Antarctica, during the 19th Italica expedition in February 2004. This is the second species of Fissarcturus from the Ross Sea after F. rossi Brandt, 2007. F. walteri sp. nov. is most similar to Fissarcturus granulosus (Nordenstam, 1933) from South Georgia but can be distinguished by the blunt short, anteriorly directed supraocular spines and elevations and some other characters as described herewith.


COHORT CHANGES IN THE SOCIAL DISTRIBUTION OF TOLERANT SEXUAL ATTITUDES.
Though many studies have described societal-wide changes in tolerance for sexual behaviors outside marriage, few have examined how the social distribution of tolerant attitudes has changed. A diffusion-of-innovations approach predicts nonlinear change in the distribution: high SES groups adopt the attitudes first, which produces a positive relationship, but diffusion to other SES groups subsequently weakens the association with SES. I test this argument using the General Social Survey from 1973 to 2014 to compare the SES determinants of attitudes toward premarital sex, extramarital sex, same-gender sex, and teenage sex across 86 cohorts born from around 1900 to 1985. Multilevel age, period, and cohort models support diffusion arguments concerning tolerance of premarital sex by demonstrating that the effects of indicators of SES first strengthen and then weaken across cohorts. Little support emerges for diffusion arguments concerning tolerance of extramarital sex and teenage sex, and preliminary but suggestive support emerges concerning tolerance of same-gender sex.


Online Recruitment: Feasibility, Cost, and Representativeness in a Study of Postpartum Women.
Online recruitment is feasible, low-cost, and can provide high-quality epidemiological data. However, little is known about the feasibility of recruiting postpartum women online, or sample representativeness. The current study investigates the feasibility of recruiting a population of postpartum women online for health research and examines sample representativeness. Two samples of postpartum women were compared: those recruited online as participants in a brief survey of new mothers (n=1083) and those recruited face-to-face as part of a nationally representative study (n=579). Sociodemographic, general health, and mental health characteristics were compared between the two samples. Obtaining a sample of postpartum women online for health research was highly efficient and low-cost. The online sample over-represented those who were younger (aged 25-29 years), were in a de facto relationship, had higher levels of education, spoke only English at home, and were first-time mothers. Members of the online sample were significantly more likely to have poor self-rated health and poor mental health than the nationally representative sample. Health differences remained after adjusting for sociodemographic differences. Potential exists for feasible and low-cost e-epidemiological research with postpartum populations; however, researchers should consider the potential influence of sample nonrepresentativeness.


Sparsity Is Better with Stability: Combining Accuracy and Stability for Model Selection in Brain Decoding.
Structured sparse methods have received significant attention in neuroimaging. These methods allow the incorporation of domain knowledge through additional spatial and temporal constraints in the predictive model and carry the promise of being more interpretable than non-structured sparse methods, such as LASSO or Elastic Net methods. However, although sparsity has often been advocated as leading to more interpretable models it can also lead to unstable models under subsampling or slight changes of the experimental conditions. In the present work we investigate the impact of using stability/reproducibility as an additional model selection criterion on several different sparse (and structured sparse) methods that have been recently applied for fMRI brain decoding. We compare three different model selection criteria: (i) classification accuracy alone; (ii) classification accuracy and overlap between the solutions; (iii) classification accuracy and correlation between the solutions. The methods we consider include LASSO, Elastic Net, Total Variation, sparse Total Variation, Laplacian and Graph Laplacian Elastic Net (GraphNET). Our results show that explicitly accounting for stability/reproducibility during the model optimization can mitigate some of the instability inherent in sparse methods. In particular, using accuracy and overlap between the solutions as a joint optimization criterion can lead to solutions that are more similar in terms of accuracy, sparsity levels and coefficient maps even when different sparsity methods are considered.


Effect of dietary fat content on microvillus in rat jejunum.
To examine whether dietary manipulation of isoenergic diets might affect microvillar structure of small intestinal epithelial cells, morphological parameters of enterocytes and microvilli in the mid-villus portion of jejunum were determined in the rats fed either high-starch (70 energy %), low-fat (7 energy %) diet or high-fat (73 energy %), low-starch (5 energy %) diet for 7 days. Feeding the high-fat diet produced an increase in the height of villus, in accordance with the elevated jejunal mucosal weight and total protein contents as compared with the high-starch diet. No appreciable change in crypt depth occurred. Scanning electron microscopy of jejunal epithelial cells revealed that the morphometrical parameters of the villus cells were unchanged by the diets, but the microvillar structure of each villus cell was influenced by the diets; the animals fed the high-fat diet exhibited a reduced length (28%) of microvillus with a slight increase (12%) in diameter, showing a significantly reduced surface area of microvilli per enterocyte. The reduction in microvillar surface area of animals fed the high-fat diet was accompanied by the decrease in total proteins of the brush border membranes as well as the decrease in the activities of microvillar stalked disaccharidases, i.e., sucrase-isomaltase and lactase. These results provide an evidence that dietary manipulation, even when diets are "complete" in terms of the content of energy, protein, and other micronutrients, can modify the microvillar structure of small intestinal epithelial cells, leading to alterations in the digestive/absorptive surface area of villus cells.


Regulating the Silicon/Hematite Microwire Photoanode by the Conformal Al2O3 Intermediate Layer for Water Splitting.
Dual-absorber photoelectrodes have been proved to possess greater potential than the single-absorber systems in the applications of photoelectrochemical (PEC) cells (e.g., solar-driven water splitting); however, the mismatching of the energy bands and substantial carrier recombinations at the two absorber interfaces are normally subsistent. Here, we introduce an intermediate layer of conformal Al2O3 into the silicon/hematite (Si/α-Fe2O3) microwire photoanode for enriching the understanding of the interaction among the interlayer, inner absorber, and outer absorber. Our results show that the Si/Al2O3/α-Fe2O3 microwire photoanode with the thickness-optimized Al2O3 can lead to a substantial increase in the photocurrent from 0.83 to 2.08 mA/cm2 at 1.23 VRHE (under 1 sun irradiation) and an obvious decrease in the onset potential relative to the counterpart without Al2O3. By analyzing the PEC responses under various monochromatic lights, PEC impedance spectroscopy, and intensity-modulated photocurrent spectroscopy, we ascribe the improvements to the fact that the suitable-thickness Al2O3 can passivate the Si microwire surfaces and the bottom surfaces of the α-Fe2O3 film and give rise to Al doping into the post-synthesized α-Fe2O3. These essential causes promote the carrier separation in α-Fe2O3, diminish the photoanode surface recombination rate, and then increase the surface charge-transfer efficiency.


Placebo and deception: a commentary.
In a recent article in this Journal, Shlomo Cohen and Haim Shapiro (2013) introduce the concept of "comparable placebo treatments" (CPTs)--placebo treatments with biological effects similar to the drugs they replace--and argue that doctors are not being deceptive when they prescribe or administer CPTs without revealing that they are placebos. We critique two of Cohen and Shapiro's primary arguments. First, Cohen and Shapiro argue that offering undisclosed placebos is not lying to the patient, but rather is making a self-fulfilling prophecy--telling a "lie" that, ideally, will become true. We argue that offering undisclosed placebos is not a "lie" but is a straightforward case of deceptively misleading the patient. Second, Cohen and Shapiro argue that offering undisclosed CPTs is not equivocation. We argue that it typically is equivocation or deception of another sort. If justifiable, undisclosed placebo use will have to be justified as a practice that is deceptive in most instances.


Adverse reactions to whole blood donation and plasmapheresis.
Whole blood donation is recognized to be extremely safe, yet there have been reports of serious problems stemming from whole blood donation, and so-called "donor reactions" are regularly seen. While the physiologic causes of the common donor reactions are not completely understood, some effects of whole blood donation (such as transient iron deficiency) are understood but probably not significant. In order to avoid accepting any volunteer donor who might be at risk of a serious reaction, we may have been overly cautious in exclusion of potential donors. The pheresis donor is subjected to potential depletion of the protein or cellular elements being removed, problems caused by the device used for automated pheresis, or problems related to the infusion of potentially toxic substances. Documented benefit to the patient must balance these additional risks.


Variability in DNA Repair Capacity Levels among Molecular Breast Cancer Subtypes: Triple Negative Breast Cancer Shows Lowest Repair.
Breast cancer (BC) is a heterogeneous disease which many studies have classified in at least four molecular subtypes: Luminal A, Luminal B, HER2-Enriched, and Basal-like (including triple-negative breast cancer, TNBC). These subtypes provide information to stratify patients for better prognostic predictions and treatment selection. Individuals vary in their sensitivities to carcinogens due to differences in their DNA repair capacity (DRC) levels. Although our previous case-control study established low DRC (in terms of NER pathway) as a BC risk factor, we aim to study this effect among the molecular subtypes. Therefore, the objectives of this study include investigating whether DRC varies among molecular subtypes and testing any association regarding DRC. This study comprised 267 recently diagnosed women with BC (cases) and 682 without BC (controls). Our results show a substantial variability in DRC among the molecular subtypes, with TNBC cases (n = 47) having the lowest DRC (p-value < 0.05). Almost 80 percent of BC cases had a DRC below the median (4.3%). Low DRC was strongly associated with the TNBC subtype (OR 7.2; 95% CI 3.3, 15.7). In conclusion, our study provides the first report on the variability among the molecular subtypes and provides a hypothesis based on DRC levels for the poor prognosis of TNBC.


The paucity of minimal change disease in adolescents with primary nephrotic syndrome.
Data are sparse regarding the histological lesions associated with the primary nephrotic syndrome in adolescents. To our knowledge there are only two published articles that have specifically addressed the histopathological lesions that typify idiopathic nephrotic syndrome in the adolescent population. We reviewed our experience from the last 14 years of children between the ages of 12 and 18 years who were referred to our center for the evaluation of the nephrotic syndrome. A total of 29 adolescents met the inclusion criteria for this review. All patients were biopsied prior to the initiation of treatment. The sex ratio consisted of 52% males and 48% females and the racial breakdown was largely African-American, with 83% black adolescents, 7% Hispanic, and 10% Caucasian patients. Minimal change nephrotic syndrome (MCNS), the predominant lesion of children at an early age, was noted in only 20% of patients. The majority of patients (55.2%) had focal segmental glomerulosclerosis (FSGS); 7% had IgM nephropathy and 3.5% had diffuse mesangial hypercellularity. Only 7% of biopsied adolescents had membranoproliferative glomerulonephritis. Our results indicate that the most common lesion in this predominantly African-American patient population is FSGS, with only a small number showing MCNS. Thus, in our experience derived from a racially mixed population, adolescents with the nephrotic syndrome are less likely to have MCNS than younger children.


Interrelation of different oto-acoustic emissions.
Amplitude and phase of the sound pressure measured in the closed ear canal during stimulation with pure tones have been monitored as a function of frequency for subjects with and without measurable spontaneous emissions. The frequency spacing between neighboring maxima of the evoked emissions is closely related to that found between neighboring spontaneous emissions. Similar data are found with delayed evoked emissions. All three catagories , spontaneous, delayed, and synchronous evoked emissions are closely related to each other and to the fine structure of threshold in quiet.


Binding and degradation of alpha 2-macroglobulin by cultured fibroblasts.
We studied the interactions of alpha 2-macroglobulin, a major protease inhibitor of plasma and of serum-containing culture medium, with cultured fibroblasts. Iodinated human alpha 2-macroglobulin bound specifically to washed cell layers of cultured human fibroblasts. At 0--4 degrees C, binding was saturated at a concentration of 10--20 micrograms/ml. At 37 degrees C, radiolabel appeared in the medium in a form soluble in 10% trichloroacetic acid. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that ingested iodinated alpha 2-macroglobulin transiently forms a complex with a trypsin-like protease. Indirect immunofluorescence demonstrated alpha 2-macroglobulin in vacuoles of fibroblasts grown in 10% human serum or incubated with purified alpha 2-macroglobulin. Fibroblasts transformed by SV-40 (VA-13 cells) bound and degraded less 125I-labeled alpha 2-macroglobulin than non-transformed fibroblasts and had fewer vacuoles containing alpha 2-macroglobulin. These observations indicate that cultured fibroblasts bind, take up by endocytosis, and degrade alpha 2-macroglobulin. Binding and endocytosis of alpha 2-macroglobulin by a cell may be a means of modulating proteases in the microenvironment of the cell and during endocytosis.


Analysis of volatile compounds in beef fat by dynamic-headspace solid-phase microextraction combined with gas chromatography-mass spectrometry.
A solid-phase microextraction (SPME) technique has been applied to the determination of the volatile compounds, including diterpenoids and lactones, in cooked beef fat. The ability of static-headspace SPME to extract lactones was disappointing, regardless of the type of SPME fiber or the temperature used. Dynamic-headspace SPME extraction with 50-/30-microm divinylbenzene-Carboxen on a polydimethylsiloxane fiber at 100 degrees C, by contrast, enabled the analysis of volatiles, including delta-lactones, gamma-lactones, and diterpenoids, with 50-/30-microm divinylbenzene-Carboxen on a polydimethylsiloxane fiber at 100 degrees C. Fifty-three compounds were identified from only 0.20 g of rendered beef fat, and 76% of these showed reliable peak size repeatability: the coefficient of variation was less than 10% on the total ion chromatograms obtained from gas chromatography-mass spectrometry (GC-MS) analysis. Some lactones showed higher CV values (>10%), but single-ion mode GC-MS analysis reduced them to 10% or less. In a study of beef samples available to the Japanese market, our analytical procedure revealed significantly higher levels of 1-hexanol, octadecane, ethyl tetradecanoate, gamma-nonalactone, but lower levels of delta-decalactone, delta-dodecalactone, and neophytadiene, in Japanese Black cattle than in beef imported from Australia.


Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats.
Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.


Oviposition preference and larval performance of Epiphyas postvittana (Lepidoptera: Tortricidae) on Botrytis cinerea (Helotiales: Sclerotiniaceae) infected berries of Vitis vinifera (Vitales: Vitaceae).
In this paper we tested the behavior of gravid Epiphyas postvittana in selecting the most-appropriate site for oviposition thus benefitting offspring performance. Our hypothesis was built on Jaenike's preference-performance hypothesis (also referred to as the "mother-knows-the-best" hypothesis). To test this, we used the interacting Epiphyas postvittana, its host Vitis vinifera, and the pathogenic microbe Botrytis cinerea system. Populations of E. postvittana and B. cinerea often exist concurrently on V. vinifera in Australasia and their interaction and mutual influence are currently being explored, although the suggestion presently is that the relationship between E. postvittana and B. cinerea is mutualistic. We tested the effect of volatiles from B. cinerea-infected berries and uninfected (control) berries of V. vinifera on the oviposition behavior of E. postvittana. We also characterized the effects of B. cinerea infection on the berries of V. vinifera on the growth and development of E. postvittana. Contrary to the preference-performance hypothesis, oviposition choices made by gravid E. postvittana did not result in the best offspring survival, development, and performance. The preference for oviposition by E. postvittana was strongly influenced by the olfactory and tactile cues. She laid fewer eggs on B. cinerea-infected berries compared to uninfected berries of V. vinifera. The larvae of E. postvittana showed no preference to uninfected berries of V. vinifera. The larvae fed on B. cinerea-infected berries of V. vinifera showing greater survival rate, shorter time to pupation, greater pupal mass, and on becoming adults they laid more numbers of eggs than the larvae that were enabled to feed on uninfected berries. The larvae of E. postvittana transport the conidia of B. cinerea and transmit grey-mould disease to uninfected berries of V. vinifera.


An overview of permanent and temporary cardiac pacemakers.
As pacemaker technology comes closer to mimicking the heart's own pacing system, patients in need of such devices can hope to live increasingly normal and productive lives. This article outlines common types of cardiac pacing and indications for pacemaker insertion. Nursing considerations are outlined both during and following the insertion of a pacemaker.


Effects of the resin and smoke condensate of Cannabis sativa on the oestrous cycle of the rat.
This study is concerned with variations in the oestrous cycle of the Sprague-Dawley rat following the intraperitoneal administration of maize oil solutions of Cannabis sativa resin and smoke condensate in doses of 10 and 20 mg/kg. Oestrus was shortened with doses of both the resin and the smoke condensate, whereas dioestrus was lengthened with the 20 mg/kg smoke condensate. ALso observed was a lengthening of postoestrus following the administration of 20 mg/kg of either the resin or the smoke condensate.


PanKmer: k-mer-based and reference-free pangenome analysis.
Pangenomes are replacing single reference genomes as the definitive representation of DNA sequence within a species or clade. Pangenome analysis predominantly leverages graph-based methods that require computationally intensive multiple genome alignments, do not scale to highly complex eukaryotic genomes, limit their scope to identifying structural variants (SVs), or incur bias by relying on a reference genome. Here, we present PanKmer, a toolkit designed for reference-free analysis of pangenome datasets consisting of dozens to thousands of individual genomes. PanKmer decomposes a set of input genomes into a table of observed k-mers and their presence-absence values in each genome. These are stored in an efficient k-mer index data format that encodes SNPs, INDELs, and SVs. It also includes functions for downstream analysis of the k-mer index, such as calculating sequence similarity statistics between individuals at whole-genome or local scales. For example, k-mers can be "anchored" in any individual genome to quantify sequence variability or conservation at a specific locus. This facilitates workflows with various biological applications, e.g. identifying cases of hybridization between plant species. PanKmer provides researchers with a valuable and convenient means to explore the full scope of genetic variation in a population, without reference bias. PanKmer is implemented as a Python package with components written in Rust, released under a BSD license. The source code is available from the Python Package Index (PyPI) at https://pypi.org/project/pankmer/ as well as Gitlab at https://gitlab.com/salk-tm/pankmer. Full documentation is available at https://salk-tm.gitlab.io/pankmer/.


Changes in Sprint Force-Velocity Profile in International Para Footballers.
Force production is crucial in football, and it is the main limitation of people with cerebral palsy (CP). This study aimed to describe the changes in sprint force-velocity (Fv) profile after a period of 25 weeks of regular training in international football players with CP. The sprint Fv profile and other physical performance variables (ie, linear sprint, vertical jump, change of direction, and intermittent endurance) of 14 international players from the Spanish national team were assessed during 2 consecutive training camps. Pretesting and posttesting sessions were carried out 1 week before and after the 25-week intervention period. The intervention consisted of 2 strength sessions per week added to the usual football training. The repeated-measures analysis of variance showed changes in players' physical performance (linear sprint: F = 18.05, P < .01; change of direction: F = 16.71, P < .01; and endurance: F = 31.45, P < .01) and in some variables of the sprint Fv profile (maximal horizontal force, maximal power, slope, maximal ratio of force, and decrease of ratio of force; F = 14.28-37.81; P < .01), whereas players' maximal velocity (theoretical and actual) did not change (F = 0.13 and 0.01; P = .72 and .98, respectively). This study showed that the implementation of 2 strength-training sessions per week, for 25 weeks, is effective to improve CP football players' physical performance. The main finding of this study is the improvement of force application in the acceleration phase (sprint Fv profile), which is the main attribute in many physical performance tests and is the main limitation of the CP population.


TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer.
Point mutations in the AR ligand-binding domain (LBD) can result in altered AR structures leading to changes of ligand specificity and functions. AR mutations associated to prostate cancer (PCa) have been shown to result in receptor activation by non-androgenic substances and anti-androgenic drugs. Two AR mutations known to alter the function of anti-androgens are the ART877A mutation, which is frequently detected mutation in PCa tumors and the ARW741C that is rare and has been derived in vitro following exposure of cells to the anti-androgen bicalutamide. AR activation by non-androgenic environmental substances has been suggested to affect PCa progression. In the present study we investigated the effect of AR mutations (ARW741C and ART877A) on the transcriptional activation following exposure of cells to an androgenic brominated flame retardant, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH, also named DBE-DBCH). The AR mutations resulted in higher interaction energies and increased transcriptional activation in response to TBECH diastereomer exposures. The ART877A mutation rendered AR highly responsive to low levels of DHT and TBECH and led to increased AR nuclear translocation. Gene expression analysis showed a stronger induction of AR target genes in LNCaP cells (ART877A) compared to T-47D cells (ARWT) following TBECH exposure. Furthermore, AR knockdown experiments confirmed the AR dependency of these responses. The higher sensitivity of ART877A and ARW741C to low levels of TBECH suggests that cells with these AR mutations are more susceptible to androgenic endocrine disrupters.


Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis.
Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1.


A new amidrazone derivative with antimycobacterial activity.
Of a series of pyridine-2-carboxamidrazone derivatives with activity against mycobacteria, the N(1)-[4-(1,1-dimethylpropyl)benzylidene] derivative reported here, C(18)H(22)N(4), is one of the most active. The predicted E isomer about the C11=N12 double bond is confirmed and intramolecular hydrogen bonding involving both amino H atoms helps to keep the molecule flat. The same donor and acceptor atoms also form intermolecular hydrogen bonds.


Development and Feasibility of an Academic Detailing Intervention to Improve Prescription Drug Monitoring Program Use Among Physicians.
South Carolina (SC) ranks 10th in opioid prescriptions per capita-33% higher than the national average. SC is also home to a large military and veteran population, and prescription opioid use for chronic pain is alarmingly common among veterans, especially those returning from Afghanistan and Iraq. This article describes the background and development of an academic detailing (AD) educational intervention to improve use of a Prescription Drug Monitoring Program among SC physicians who serve military members and veterans. The aim of this intervention was to improve safe opioid prescribing practices and prevent prescription opioid misuse among this high-risk population. A multidisciplinary study team of physicians, pharmacists, psychologists, epidemiologists, and representatives from the SC's Prescription Monitoring Program used the Medical Research Council complex interventions framework to guide the development of the educational intervention. The theoretical and modeling phases of the AD intervention development are described and preliminary evidence of feasibility and acceptability is provided. Ninety-three physicians consented to the study from 2 practice sites. Eighty-seven AD visits were completed, and 59 one-month follow-up surveys were received. Participants rated the AD intervention high in helpfulness of information, intention to use information, and overall satisfaction with the intervention. The component of the intervention felt to be most helpful was the AD visit itself. Characteristics of the participants and the intervention, as well as anticipated barriers to behavior change are detailed. Preliminary results support the feasibility of AD delivery to veteran and community patient settings, the feasibility of facilitating Prescription Drug Monitoring Program registration during an AD visit, and that AD visits were generally found satisfying to participants and helpful in improving knowledge and confidence about safe opioid prescribing practices. The component of the intervention felt to be most helpful to the participants was the actual AD visit, and most participants rated their intentions high to use the information and tools from the visit. Intervention key messages, preliminary outcome measures, and successes and challenges in developing and delivering this intervention are discussed to advance best practices in developing educational interventions in this important area of public health.


Decreased expression of Ku70/Ku80 proteins in malignant melanomas of the oral cavity.
Ku70/80 are genes responsible for the repairing of DNA double-strand breaks and they function as a regulatory subunit of the DNA-dependent protein kinase. Their expression has not yet been investigated in malignant melanomas of the oral cavity. These tumours are characterized by very poor prognosis and etiology independent of UV-radiation. We investigated 29 malignant melanomas of the oral cavity for the expression of Ku70/80 proteins. Ku70 expression was preserved in 21 out of 29 tumours and the percentage of Ku70-positive cells did not exceed 76%. Ku80 was found in 19 out of 29 tumours and the percentage of Ku80-positive cells peaked at 62%. Correlations between Ku70 and Ku80 expression were lost (p>0.05). We conclude that decreased Ku70/80 expression in malignant melanomas of the oral cavity and loss of correlation between these markers may influence progression of oral melanomas.


Which Technique Is Better for Treating Patellar Dislocation? A Systematic Review and Meta-analysis.
To clarify the discrepancy in surgical options and present evidence to treat patellar dislocation by evaluating which of the techniques yields better improvement in stability and functional recovery for patellar dislocation. The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus electronic databases were searched for relevant articles comparing the outcomes of medial patellofemoral ligament (MPFL) treatment published up until August 2017. Data searching, extraction, analysis, and quality assessment were performed based on The Cochrane Collaboration guidelines. Clinical outcomes were evaluated using various outcome values in various techniques. For results with high heterogeneity, 95% prediction intervals (PIs) were also investigated. Eleven clinical studies were investigated. In patients with primary patellar dislocation, there were no significant differences in all evaluated outcomes between the conservative and surgical treatment groups. For patients with recurrent patellar dislocation, MPFL reconstruction was associated with a favorable Kujala score (mean difference, -8.91; 95% confidence interval, -14.05 to -3.77; I2 = 94%; 95% PI, -9.64 to -8.1) and Lysholm score (mean difference, -13.51; 95% confidence interval, -21.35 to -5.68; I2 = 96%; 95% PI, -14.86 to -12.16) when compared with soft tissue realignment surgery. Although surgical treatment of the MPFL for primary patellar dislocation is not superior to conservative treatment in restoring knee function and clinical outcomes, MPFL reconstruction is associated with more favorable clinical outcomes compared with medial soft tissue realignment surgery in patients with recurrent patellar dislocation. Double-bundle MPFL reconstruction seems to provide more favorable outcomes than single-bundle MPFL reconstruction, but this finding should be interpreted with caution because the evidence levels were low and were from only a few studies. Level III, meta-analysis.


Bcr/abl recombinant DNA analysis versus karyotype in the diagnosis and therapeutic monitoring of chronic myeloid leukemia.
Karyotype and bcr/abl recombinant DNA analyses are two means of detecting the chromosomal aberration in chronic myeloid leukemia. The authors compared these two methods in a retrospective study of 36 patients with CML in which they found the bcr/abl DNA recombinant event in 100% (29 of 29) of those patients who had the Philadelphia chromosome. To achieve this sensitivity, a battery of two bcr probes and three restriction enzymes is necessary. The authors propose a sequential algorithm for efficient use of these probes and enzymes. In 76% of the patients, bcr/abl rearrangement can be detected with a Bgl II digest and a 3' commercial probe. An additional 21% of patients can be detected by a second assay in which the same membrane is rehybridized to a 3' and 5' combination bcr probe. One patient (3%) required an additional restriction enzyme digest with BamH I to detect the recombinant event by the same 3' probe. Karyotype analysis is used to determine cytogenetic remission in patients with CML under therapy. The authors studied the use of DNA analysis by the Southern blot technique to detect a decrease in the relative number of leukemic cells. By dilution studies and densitometric scanning of autoradiographs, the authors were able to detect a 15% decrease in the relative number of cells having the bcr/abl recombinant event. The authors report the preliminary results of three patients in whom they compared the karyotype and recombinant DNA analysis at multiple time points in their clinical course. In conclusion, the bcr/abl recombinant DNA analysis is superior to karyotype for the diagnosis of CML and can be used for monitoring treated patients.


Lack of SYT-SSX fusion transcripts in malignant peripheral nerve sheath tumors on RT-PCR analysis of 34 archival cases.
The translocation t(X;18) is currently regarded as a specific molecular marker of synovial sarcoma (SS). Recently, however, it has been reported that malignant peripheral nerve sheath tumors expressed this marker in 75% of the cases. To test independently this iconoclastic claim, a molecular analysis for the detection of the SYT-SSX fusion genes was carried out using archival material of 34 consecutive cases diagnosed as malignant peripheral nerve sheath tumors and treated in our Institute from 1998 to 2000. In four of these cases, the molecular analysis on fixed tissues was supplemented with an analysis on fresh frozen tissue. RNA extracted from formalin-fixed paraffin-embedded tissue blocks was evaluated for the presence of SYT-SSX1 and SYT-SSX2 fusion transcripts by RT-PCR. This analysis was extended to a wide variety of normal tissues simultaneously extracted and equally processed. Only two of the cases studied harbored SYT-SSX1 and SYT-SSX2 fusion transcripts, respectively. The diagnostic reevaluation of these two cases in light of the molecular data disclosed that one had the features of a monophasic SS and the other was compatible with that entity. Both of these tumors were strongly immunoreactive for bcl-2, confirming the diagnostic utility of this marker in this instance. Our results reaffirm the specificity of SYT-SSX for SS and suggest that an opposite claim made in a recent study may have been due to a faulty interpretation of the molecular results caused by a contamination of the samples.


DASH cryptochrome 1, a UV-A receptor, balances the photosynthetic machinery of Chlamydomonas reinhardtii.
Drosophila, Arabidopsis, Synechocystis, Homo (DASH) cryptochromes belong to the cryptochrome/photolyase family and can act as DNA repair enzymes. In bacteria and fungi, they also can play regulatory roles, but in plants their biological functions remain elusive. Here, we characterize CRY-DASH1 from the green alga Chlamydomonas reinhardtii. We perform biochemical and in vitro photochemical analysis. For functional characterization, a knock-out mutant of cry-dash1 is used. CRY-DASH1 protein is localized in the chloroplast and accumulates at midday. Although the photoautotrophic growth of the mutant is significantly reduced compared to the wild-type (WT), the mutant has increased levels of photosynthetic pigments and a higher maximum photochemical efficiency of photosystem II (PS II). Hyper-stacking of thylakoid membranes occurs together with an increase in proteins of the PS II reaction center, D1 and its antenna CP43, but not of their transcripts. CRY-DASH1 binds fully reduced flavin adenine dinucleotide and the antenna 5,10-methenyltetrahydrofolate, leading to an absorption peak in the UV-A range. Supplementation of white light with UV-A increases photoautotrophic growth of the WT but not of the cry-dash1 mutant. These results suggest a balancing function of CRY-DASH1 in the photosynthetic machinery and point to its role as a photoreceptor for the UV-A range separated from the absorption of photosynthetic pigments.


Receptor-independent Ambient pH signaling by ubiquitin attachment to fungal arrestin-like PalF.
The seven-transmembrane receptor PalH and its coupled, positive-acting arrestin-like protein PalF are key components of a molecular sensor that in Aspergillus nidulans and other ascomycete fungi mediates activation of an intracellular signaling cascade by alkaline ambient pH. PalF is ubiquitinated in an alkaline pH- and PalH-dependent manner. We show here that PalF assists the plasma membrane localization of PalH and that PalF overexpression slightly hypersensitizes the pathway to alkaline pH but does not bypass the need for the ambient pH signal receptor in signaling. In contrast, covalent attachment of Ub to PalF activates the signaling pathway under acidic pH conditions in which the pathway is normally inactive, demonstrating a positive role for ubiquitination. We further show that PalF acts upstream of, or in concert with, the Bro1 domain-containing pH signaling protein PalC, which is normally recruited to cortical structures likely to represent active pH signaling foci under neutral/alkaline pH conditions. In agreement with its pathway-activating consequences, expression of PalF-Ub also promotes PalC cortical recruitment under acidic conditions. Notably, our data establish that expression of PalF-Ub, at approximately physiological levels, in a null palH background leads to a considerable degree of signaling even in the complete absence of the receptor. Thus PalF ubiquitination is a key, perhaps the sole, molecular trigger required for transmitting the alkaline pH signal to the downstream elements of the pathway.


Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model.
Critically ill patients frequently have substantially altered pharmacokinetics compared to non-critically ill patients. We investigated the impact of pharmacokinetic alterations on bacterial killing and resistance for commonly used meropenem dosing regimens. A Pseudomonas aeruginosa isolate (MICmeropenem 0.25 mg/liter) was studied in the hollow-fiber infection model (inoculum ∼107.5 CFU/ml; 10 days). Pharmacokinetic profiles representing critically ill patients with augmented renal clearance (ARC), normal, or impaired renal function (creatinine clearances of 285, 120, or ∼10 ml/min, respectively) were generated for three meropenem regimens (2, 1, and 0.5 g administered as 8-hourly 30-min infusions), plus 1 g given 12 hourly with impaired renal function. The time course of total and less-susceptible populations and MICs were determined. Mechanism-based modeling (MBM) was performed using S-ADAPT. All dosing regimens across all renal functions produced similar initial bacterial killing (≤∼2.5 log10). For all regimens subjected to ARC, regrowth occurred after 7 h. For normal and impaired renal function, bacterial killing continued until 23 to 47 h; regrowth then occurred with 0.5- and 1-g regimens with normal renal function (fT>5×MIC = 56 and 69%, fCmin/MIC < 2); the emergence of less-susceptible populations (≥32-fold increases in MIC) accompanied all regrowth. Bacterial counts remained suppressed across 10 days with normal (2-g 8-hourly regimen) and impaired (all regimens) renal function (fT>5×MIC ≥ 82%, fCmin/MIC ≥ 2). The MBM successfully described bacterial killing and regrowth for all renal functions and regimens simultaneously. Optimized dosing regimens, including extended infusions and/or combinations, supported by MBM and Monte Carlo simulations, should be evaluated in the context of ARC to maximize bacterial killing and suppress resistance emergence.


The performance of different propensity score methods for estimating marginal odds ratios.
The propensity score which is the probability of exposure to a specific treatment conditional on observed variables. Conditioning on the propensity score results in unbiased estimation of the expected difference in observed responses to two treatments. In the medical literature, propensity score methods are frequently used for estimating odds ratios. The performance of propensity score methods for estimating marginal odds ratios has not been studied. We performed a series of Monte Carlo simulations to assess the performance of propensity score matching, stratifying on the propensity score, and covariate adjustment using the propensity score to estimate marginal odds ratios. We assessed bias, precision, and mean-squared error (MSE) of the propensity score estimators, in addition to the proportion of bias eliminated due to conditioning on the propensity score. When the true marginal odds ratio was one, then matching on the propensity score and covariate adjustment using the propensity score resulted in unbiased estimation of the true treatment effect, whereas stratification on the propensity score resulted in minor bias in estimating the true marginal odds ratio. When the true marginal odds ratio ranged from 2 to 10, then matching on the propensity score resulted in the least bias, with a relative biases ranging from 2.3 to 13.3 per cent. Stratifying on the propensity score resulted in moderate bias, with relative biases ranging from 15.8 to 59.2 per cent. For both methods, relative bias was proportional to the true odds ratio. Finally, matching on the propensity score tended to result in estimators with the lowest MSE.


Nanoscale Tipping Bucket Effect in a Quantum Dot Transistor-Based Counter.
Electronic circuits composed of one or more elements with inherent memory, that is, memristors, memcapacitors, and meminductors, offer lower circuit complexity and enhanced functionality for certain computational tasks. Networks of these elements are proposed for novel computational paradigms that rely on information processing and storage on the same physical platform. We show a nanoscaled memdevice able to act as an electronic analogue of tipping buckets that allows reducing the dimensionality and complexity of a sensing problem by transforming it into a counting problem. The device offers a well adjustable, tunable, and reliable periodic reset that is controlled by the amounts of transferred quantum dot charges per gate voltage sweep. When subjected to periodic voltage sweeps, the quantum dot (bucket) may require up to several sweeps before a rapid full discharge occurs thus displaying period doubling, period tripling, and so on between self-governing reset operations.


Critical Index of Difficulty for Different Body Motions: A Review.
K.-C. Gan and E. R. Hoffmann (1988) demonstrated that there is a clear boundary between values of Fitts' index of difficulty (ID) below which movements may be made without ongoing path corrections; above this value it was necessary to use corrections to hit a target of high ID. It is shown that this critical ID (IDcrit) value is dependent on both the body component making the movement and on the form of feedback available to the person. The arm system, having the highest ratio of muscle strength to mass moment of inertia, has the highest value of IDcrit, whereas control of the body center of mass location has the lowest value of IDcrit. It is suggested that the use of visual control to lower ID values with the larger body components is due to the longer movement times available because of the physical characteristics of these components-the time is available, and therefore it is used to make path corrections.


Quantification and characterization of aortic cholesterol in rabbits fed a high-cholesterol diet.
Determination of fat percentage of aortic intimal area stained by Sudan III is useful as an index of atherosclerosis in the rabbit animal model. However, the determination of sudanophilic area of the thoracic aorta is two-dimensional and does not measure the third dimension of depth. The objective of the present study was to quantify and characterize aortic lipids using the gas-liquid chromatographic (GLC) technique and to determine whether elevated measurements of total cholesterol and cholesteryl esters was correlated with increased measurements of sudanophilic area staining of the thoracic aorta in rabbits given either a normal chow or a 1% cholesterol diet. The GLC results showed that there was a mean accumulation of 10.9 mg of cholesterol per gram of aortic tissue in the rabbits given a cholesterol diet (mean sudanophilic area of 23.8%). In contrast, rabbits on a normal chow diet had only a deposition of 0.58 mg of cholesterol per gram of the aortic tissue diet (mean sudanophilic area of 1.4%). The present study suggests that quantification of the aortic lipids can be performed by using GLC techniques and that it could be used as an alternative to the measurement of sudanophilic area when assessing the severity of atherosclerosis.


Risk Factors of Suicide Death Based on Psychological Autopsy Method; a Case-Control Study.
Investigation in each community can contribute to understanding the key factors involved in suicide death and its prevention. The present study aimed to investigate suicide death risk factors based on psychological autopsy method. The present case-control study was conducted from April to September 2017, in Tehran, Iran, to compare two groups of people; those who died by suicide and controls (over the age of 18 years). Data were collected by one interviewer via Structured Clinical Interviews (SCID-I), questionnaires used in the SUPREMISS study, and the Dickman impulsivity scale. Each group consisted of 40 individuals. There was no significant difference between the case and control groups in terms of all demographic variables except for the level of education (p = 0.06) and occupational status (p = 0.009). The frequency of previous history of suicide attempt (p = 0.001), family history of suicide (p = 0.003), DSM IV Axis I disorders (p = 0.006), and substance and alcohol consumption (p = 0.01) were significantly higher in the case group. The most commonly diagnosed disorders included MDD (45%) and substance use disorders (30%), respectively. The most common methods used in suicide included hanging (32.5%), and Aluminum phosphide poisoning (32.5%) known as rice tablet. The strongest predictor of suicide death was the deceased person's Previous history of suicide attempt (OR= 9.3; p = 0.04), smoking (OR= 6.4; p = 0.006), unemployment (OR= 5; p = 0.02), and DSM IV axis I disorders (OR= 3.8; p = 0.04). Previous suicide attempt, smoking, unemployment, and suffering from at least one mental disorder were the significant predictors of suicide death. Among mental disorders, major depressive disorder and substance use disorder were the most prevalent mental health problems.


[Study on preparation of a wound healing agent: fibronectin].
In search of the optimal preparation method for large-scale purification of human plasma fibronectin, we adopted affinity chromatography with gelatin and the Sepharose 4B activated with cyanogen bromide to purify fibronectin from type "C" plasma of healthy males, and scanned the best method under the conditions of different amount of plasma loading and different residence time in column. In a given column volume of gelatin, the absorbent was related with the plasma residence time in column and the total amount of plasma loaded. As a result, the optimal loading amount of plasma is 150 ml, and the residence time is 20 minutes. The preparation method, herein, has been proved to require small amount of plasma and yield large amount of fibronectin.


Adaptive regulation of glucose transport, glycolysis and respiration for cell proliferation.
The cell must utilise nutrients to generate energy as a means of sustaining its life. As the environment is not necessarily abundant in nutrients and oxygen, the cell must be able to regulate energy metabolism to adapt to changes in extracellular and intracellular conditions. Recently, several key regulators of energy metabolism have been reported. This review describes the recent advances in molecular regulation of energy metabolism, focusing mainly on glycolysis and its shunt pathways. Human diseases, such as cancer and neurodegenerative disorders, are also discussed in relation to failure of energy metabolism regulation.


Indication for allogeneic stem cell transplantation in Glanzmann's thrombasthenia.
Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder characterized by a lack of thrombocyte aggregation due to the absence of thrombocyte glycoproteins IIb and αIIbβ3. The role of haematopoietic stem cell transplantation (HSCT) in GT remains controversial. However, HSCT offers the only curative approach for patients with a severe clinical phenotype. In this review, we will discuss the limitation of current status evidence and the specific risk of GT, in particular the alloimmunization and refractoriness to thrombocyte infusions. 19 successful HSCT in 18 GT type I patients have been reported. Mean age at transplantation was 5 years. All patients are still alive. The majority received sibling bone marrow transplant with busulfan and cyclophosphamid conditioning. GvHD incidence was within the normal range, but 10 patients showed alloimmunization of thrombocytes. Median follow up is 25 months.


Spatial-Temporal Epidemiology of the Syphilis Epidemic in Relation to Neighborhood-Level Structural Factors in British Columbia, 2005-2016.
Spatial clusters of syphilis have been observed within several jurisdictions globally; however, the degree to which they are predicted by the spatial distributions of gay, bisexual, and other men who have sex with men (GBM) and testing remains unknown. We sought to describe the spatial-temporal epidemiology of infectious syphilis and identify associations between neighborhood-level factors and rates of syphilis, in British Columbia, Canada. We used ArcGIS to map infectious syphilis cases among men (2005 to 2016), SaTScan to detect areas with significantly elevated rates of syphilis, and spatial regression to identify associations between neighborhood-level factors and rates of syphilis. Five clusters were identified: a core in downtown Vancouver (incidence rate ratio [IRR], 18.0; 2007-2016), 2 clusters adjacent to the core (IRR, 3.3; 2012-2016; and IRR, 2.2; 2013-2016), 1 cluster east of Vancouver (IRR, 2.1; 2013-2016), and 1 cluster in Victoria (IRR, 4.3; 2015-2016). Epidemic curves were synchronized across cluster and noncluster regions. Neighborhood-level GBM population estimates and testing rates were both associated with syphilis rates; however, the spatial distribution of syphilis was not fully explained by either of these factors. We identified two novel ecologic correlates of the spatial distribution of infectious syphilis-density of GBM and rates of syphilis testing-and found that these factors partially, though not entirely, explained the spatial distribution of clusters. Residual spatial autocorrelation suggests that greater syphilis testing coverage may be needed and low-barrier GBM-affirming testing should be expanded to regions outside the core.


Representation of eye position in primate inferior colliculus.
We studied the representation of eye-position information in the primate inferior colliculus (IC). Monkeys fixated visual stimuli at one of eight or nine locations along the horizontal meridian between -24 and 24 degrees while sounds were presented from loudspeakers at locations within that same range. Approximately 40% of our sample of 153 neurons showed statistically significant sensitivity to eye position during either the presentation of an auditory stimulus or in the absence of sound (Bonferroni corrected P < 0.05). The representation for eye position was predominantly monotonic and favored contralateral eye positions. Eye-position sensitivity was more prevalent among neurons without sound-location sensitivity: about half of neurons that were insensitive to sound location were sensitive to eye position, whereas only about one-quarter of sound-location-sensitive neurons were also sensitive to eye position. Our findings suggest that sound location and eye position are encoded using independent but overlapping rate codes at the level of the IC. The use of a common format has computational advantages for integrating these two signals. The differential distribution of eye-position sensitivity and sound-location sensitivity suggests that this process has begun by the level of the IC but is not yet complete at this stage. We discuss how these signals might fit into Groh and Sparks' vector subtraction model for coordinate transformations.


Corneal biomechanical data and biometric parameters measured with Scheimpflug-based devices on normal corneas.
To analyze the correlations between ocular biomechanical and biometric data of the eye, measured by Scheimpflug-based devices on healthy subjects. Three consecutive measurements were carried out using the corneal visualization Scheimpflug technology (CorVis ST) device on healthy eyes and the 10 device-specific parameters were recorded. Pentacam HR-derived parameters (corneal curvature radii on the anterior and posterior surfaces; apical pachymetry; corneal volume; corneal aberration data; depth, volume and angle of the anterior chamber) and axial length (AL) from IOLMaster were correlated with the 10 specific CorVis ST parameters. Measurements were conducted in 43 eyes of 43 volunteers (age 61.24±15.72y). The 10 specific CorVis ST data showed significant relationships with corneal curvature radii both on the anterior and posterior surface, pachymetric data, root mean square (RMS) data of lower-order aberrations, and posterior RMS of higher-order aberrations and spherical aberration of the posterior cornea. Anterior chamber depth showed a significant relationship, but there were no significant correlations between corneal volume, anterior chamber volume, mean chamber angle or AL and the 10 specific CorVis ST parameters. CorVis ST-generated parameters are influenced by corneal curvature radii, some corneal RMS data, but corneal volume, anterior chamber volume, chamber angle and AL have no correlation with the biomechanical parameters. The parameters measured by CorVis ST seem to refer mostly to corneal properties of the eye.


Ganser-like syndrome after loss of psychic self-activation syndrome: psychogenic or organic?
Very few data are available on the long-term changes in the cognitive abilities of patients with loss of psychic self-activation syndrome (LPSAS). Here, we present a 25-year follow-up study on a case of LPSAS resulting from bilateral pallidal lesions caused by carbon monoxide intoxication. Typical signs of LPSAS were observed, showing no changes in severity, but Ganser syndrome (GS) gradually developed and worsened during the follow-up period. GS is generally assumed to be a psychogenic syndrome, but an organic etiology has been suspected by the authors of several case reports. Here, atypical features of GS plead against the independence of GS and LPSAS. DaTSCAN and brain 18FDG-PET were performed. Since left hippocampal hypometabolism has been previously described in patients with functional amnesia, it is possible that long periods of mental inactivity may have psychological consequences, but the atypical features of GS also suggest that an organic mechanism may be involved.


Stress analyses coupled with damage laws to determine biomechanical risk factors for deep tissue injury during sitting.
Deep tissue injury (DTI) is a potentially life-threatening form of pressure ulcer that onsets in muscle tissue overlying bony prominences and progresses unnoticeably to more superficial tissues. To minimize DTI, the efficacy of wheelchair cushions should be evaluated not only based on their performance in redistributing interface pressures but also according to their effects on stress concentrations in deep tissues, particularly muscles. However, a standard bioengineering approach for such analyses is missing in literature. The goals of this study were to develop an algorithm to couple finite element (FE) modeling of the buttocks with an injury threshold for skeletal muscle and with a damage-stiffening law for injured muscle tissue, from previous animal experiments, to predict DTI onset and progression for different patient anatomies and wheelchair cushions. The algorithm was also employed for identifying intrinsic (anatomical) biomechanical risk factors for DTI onset. A set of three-dimensional FE models of seated human buttocks was developed, representing different severities of pathoanatomical changes observed in chronically sitting patients: muscle atrophy and "flattening" of the ischial tuberosity (IT). These models were then tested with cushions of different stiffnesses representing products available on the market and semirigid supports. Outcome measures were the percentage of damaged muscle tissue volumes after 90 min and 110 min of simulated continuous immobilized sitting as well as muscle injury rates post-60 min, -90 min, and -110 min of continuous sitting. Damaged muscle volumes grew exponentially with the level of muscle atrophy. For example, simulation of a subject with 70% muscle atrophy sitting on a soft cushion showed damage to 33% of the muscle volume after 90 min of immobilized sitting, whereas a comparable simulation with a nonatrophied muscle yielded only 0.4% damaged tissue volume. The rates of DTI progression also increased substantially with increasing severities of muscle atrophy, e.g., 70% atrophy resulted in 8.9, 2.7, and 1.6 times greater injury rates compared with the "reference" muscle thickness cases, after 60 min, 90 min, and 110 min of sitting, respectively. Across all simulation cases, muscle injury rate was higher when a "flatter" IT was simulated. Stiffer cushions increased both the extent and rate of DTI at times shorter than 90 min of continuous sitting, but after 110 min, volumes and rates of tissue damage converged to approximately similar values across the different cushion materials. The present methodology is a practical tool for evaluating the performances of cushions in reducing the risk for DTI in a manner that goes far beyond the commonly accepted measurements of sitting pressures.


Homology dependence of UvsX protein-catalyzed joint molecule formation.
The bacteriophage UvsX protein is a "strand transferase" that promotes the pairing of homologous single and double-stranded DNAs. The efficiency of UvsX protein-mediated joint molecule formation between supercoiled duplex DNA and oligonucleotides is shown to have a sharp dependence on the degree of homology. The reaction proceeded efficiently with oligonucleotides containing 32 homologous positions but not with oligonucleotides containing only 24 homologous bases. This was shown to reflect an intrinsic homology requirement for the formation of stable joint molecules and was not caused by poor binding of the protein to short single-stranded DNAs. Even a single mismatch located in the middle of a region of 40 homologous nucleotides had a detectable effect on the efficiency of pairing. An in vitro recombinationally initiated DNA synthesis reaction that mimics the "secondary mode" of phage T4 DNA replication exhibited the same homology dependence.


Essential Thrombocythemia: The Dermatologic Point of View.
Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increase in blood platelets and dominated by a predisposition to vascular events. Cutaneous manifestations can complicate its course. itching has been the most common symptom reported; however, the percentage has ranged from 3% to 46%, depending on the survey. Erythromelalgia is found in 6% of cases, and livedo reticularis, minor bleeding, acrocyanosis, and Raynaud's phenomenon are rare manifestations. It is important to recognize and treat these events, because they can affect patients' quality of life and could worsen the prognosis. In addition to skin involvement as a possible sign of ET, the treatment of ET can be associated with cutaneous complications. Hydroxycarbamide, interferon-alfa, and anagrelide can induce different skin lesions. Hydroxycarbamide has been associated with major complications, including painful leg ulcers and actinic keratoses. Minor events include alopecia and hyperpigmentation. Xerosis, pruritus, and photosensitivity are some of the complications reported by patients treated with interferon-alfa. Anagrelide has proved to be associated with fewer dermatologic effects, only detected in single cases. Knowledge of the ET cutaneous manifestations, together with the clinical examination findings, can result in an earlier diagnosis and the start of effective treatment.


Higher Morbidity of Monogenic Inflammatory Bowel Disease Compared to the Adolescent Onset Inflammatory Bowel Disease.
Monogenic inflammatory bowel disease (IBD) patients do not respond to conventional therapy and are associated with a higher morbidity. We summarized the clinical characteristics of monogenic IBD patients and compared their clinical outcomes to that of non-monogenic IBD patients. We performed a retrospective cohort study of all children <18 years old who were diagnosed with IBD between 2005 and 2016. A total of 230 children were enrolled. Monogenic IBD was defined as a presentation age less than 6 years old with confirmation of a genetic disorder. We subdivided the groups into monogenic IBD (n=18), non-monogenic very early-onset IBD (defined as patients with a presentation age <6 years old without a confirmed genetic disorder, n=12), non-monogenic IBD (defined as all patients under 18 years old excluding monogenic IBD, n=212), and severe IBD (defined as patients treated with an anti-tumor necrosis factor excluding monogenic IBD, n=92). We compared demographic data, initial pediatric Crohn disease activity index/pediatric ulcerative colitis activity index (PCDAI/PUCAI) score, frequency of hospitalizations, surgical experiences, and height and weight under 3rd percentile among the patients enrolled. The initial PCDAI/PUCAI score (p<0.05), incidence of surgery per year (p<0.05), and hospitalization per year (p<0.05) were higher in the monogenic IBD group than in the other IBD groups. Additionally, the proportion of children whose weight and height were less than the 3rd percentile (p<0.05 and p<0.05, respectively) was also higher in the monogenic IBD group. Monogenic IBD showed more severe clinical manifestations than the other groups.


Comparison of the autonomic effects of procainamide and N-acetylprocainamide in the dog.
The autonomic effects of procainamide (PA) and N-acetylprocainamide (NAPA) were studied in anesthetized dogs. High plasma concentrations of PA (31 +/- 1.3--64 +/- 3.4 micrograms/ml) and NAPA (64 +/- 3.4--127 +/- 8.3 micrograms/ml)) reduced base-line mean arterial pressure and heart rate and attenuated the pressor and positive chronotropic responses to bilateral carotid occlusion and the negative chronotropic response to vagal stimulation. Neither drug reduced the pressor or positive chronotropic responses to catecholamines (epinephrine, phenylphrine, isoproterenol), however. In fact, at some doses PA and NAPA accentuated the pressor and positive chronotropic effects of epinephrine. Similarly, the depressor response to acetylcholine was not reduced by these drugs; it was significantly increased at some doses. In the isolated hindlimb (constant flow) PA and NAPA reduced the pressor response to preganglionic (sympathetic chain) stimulation but not to postganglionic (femoral and sciatic nerves) stimulation. We conclude that NAPA, like PA, at high plasma levels is vagolytic and attenuates baroreceptor-mediated reflexes associated with reduced arterial pressure. These effects appear to be due to ganglionic blockade.


Effects of ketamine on prefrontal and striatal regions in an overt verbal fluency task: a functional magnetic resonance imaging study.
Glutamatergic dysfunction at N-methyl-D: -aspartate (NMDA) receptors has been proposed as a neurochemical model for schizophrenia. A key feature of this disorder is impairments in cognitive function. The present study sought to investigate the effects of ketamine, an NMDA antagonist, on the performance and neural correlates of verbal fluency, a task that engages executive function. Ten healthy dextral male volunteers received intravenous placebo normal saline or ketamine (bolus of 0.23 mg/kg and infusion of 0.65 mg/kg), administered in a double-blind, randomized order, during two functional magnetic resonance imaging sessions. During scanning, subjects performed a verbal fluency task. Two levels of cognitive load were examined in the task, and overt responses were acquired in order to measure subject performance on-line. Ketamine induced symptoms in the healthy individuals comparable to an acute psychotic state. Although ketamine did not significantly impair task performance relative to placebo, an interaction of task demand with ketamine was observed in the anterior cingulate, prefrontal, and striatal regions. The behavioural and functional effects of ketamine during verbal fluency in healthy individuals were comparable to those evident in patients with schizophrenia. The findings support a role for glutamatergic dysfunction in the pathophysiology of schizophrenia.


Mesenchymal Stem Cell Senescence and Rejuvenation: Current Status and Challenges.
Over the past decades, mesenchymal stem cell (MSC)-based therapy has been intensively investigated and shown promising results in the treatment of various diseases due to their easy isolation, multiple lineage differentiation potential and immunomodulatory effects. To date, hundreds of phase I and II clinical trials using MSCs have been completed and many are ongoing. Accumulating evidence has shown that transplanted allogeneic MSCs lose their beneficial effects due to immunorejection. Nevertheless, the function of autologous MSCs is adversely affected by age, a process termed senescence, thus limiting their therapeutic potential. Despite great advances in knowledge, the potential mechanisms underlying MSC senescence are not entirely clear. Understanding the molecular mechanisms that contribute to MSC senescence is crucial when exploring novel strategies to rejuvenate senescent MSCs. In this review, we aim to provide an overview of the biological features of senescent MSCs and the recent progress made regarding the underlying mechanisms including epigenetic changes, autophagy, mitochondrial dysfunction and telomere shortening. We also summarize the current approaches to rejuvenate senescent MSCs including gene modification and pretreatment strategies. Collectively, rejuvenation of senescent MSCs is a promising strategy to enhance the efficacy of autologous MSC-based therapy, especially in elderly patients.


Association with SERCA2a directs phospholamban trafficking to sarcoplasmic reticulum from a nuclear envelope pool.
Phospholamban (PLB) stoichiometrically regulates the cardiac Ca2+ pump (SERCA2a) in the sarcoplasmic reticulum (SR); but in the nuclear envelope (NE) of cardiomyocytes (CMs), the PLB to SERCA2a molar ratio is higher, which highlights our poor understanding of how SR proteins distribute to their functional subcompartments. By tracking newly made PLB and SERCA2a in CMs, we will elucidate underlying cellular pathways responsible for their unique intracellular distributions. Highly specific monoclonal antibodies were used to compare the subcellular distributions of SERCA2a, PLB, and junctin (JCN) in dog heart tissue. The data supported a view that both non-junctional and junctional SR proteins are all prominently enriched in transverse stretches of SR tubules, along the edges of sarcomeres (SR z-tubules). To understand the genesis of these steady state distributions, we analyzed confocal immunofluorescence images of adult rat CMs after acute expression (12-48 h) of the dog ortholog of PLB (dPLB) or dSERCA2a. Newly made dog proteins in rat CMs were detected using dog-specific monoclonal antibodies. By 12-24 h, dSERCA2a had accumulated within the NE in a punctate pattern, presumably reflecting initial sites of biosynthesis. Over the next 24-48 h, higher levels of dSERCA2a immunofluorescence accumulated in transverse/radial SR tubules, aligned along sarcolemmal transverse (T)-tubules, and extending from NE puncta. The patterns of SR tubules carrying dSERCA2a overlapped with those for newly made JCN, suggesting a common Nuclear Envelope to SR along T-tubules or NEST pathway for SR proteins. In contrast to the SERCA2a distribution pattern, dPLB accumulated uniformly in the NE, without visible puncta. With co-expression of dSERCA2a, however, PLB no longer uniformly filled the NE, but instead moved together with SERCA2a to form bright NE puncta, from which the two proteins then trafficked anterogradely. Expression of dog SR protein orthologs (dSERCA2a, dPLB, and dJCN) for as little as 48 h reproduces their characteristic steady state distributions. Detailed analyses of the time courses of protein accumulation suggest a possible mechanism by which PLB distributes to both the NE and SR, unlike SERCA2a. SERCA2a moves in SR z-tubules directly from rough ER, along pathways that are in common with those used by junctional SR proteins. A different trafficking route for PLB away the rough ER/NE led to its accumulation in the NE, a process that may account for its enrichment in NE in situ. Association of SERCA2a with PLB from this NE pool enhanced PLB trafficking along the NEST pathway, contributing to steady state stoichiometry and physiologically regulated SERCA2a.


Technology Enhanced Assessment (TEA) in COVID 19 Pandemic.
Online teaching and learning is not a new phenomenon. For the last many years, it has been mainly used as a part of face to face teaching. Assessment is an essential part of teaching and learning, as it establishes the achievement of course learning outcomes by the students. Computer-based assessment is in place for a long time now, however, online assessments have been less practiced. This is because of the issues of validity, reliability and dishonesty. During the COVID 19 pandemic, the educational environment has taken a paradigm shift in many medical schools, both nationally and internationally. This situation demands a method of assessment that is safe, valid, reliable, acceptable, feasible and fair. This paper describes the different formats of online assessment and their application in formative and summative assessments during and after the COVID 19 pandemic.


Clinical, radiological and laboratory findings in 185 children with tuberculous meningitis at a single centre and relationship with the stage of the disease.
A delay in the diagnosis and treatment of tuberculosis meningitis (TBM) may lead to increased mortality and morbidity. The aim of this study was to describe the clinical, radiological and laboratory findings of TBM on a cohort of 185 pediatric patients at a single centre over a 10 year period and to investigate relationship between the stage of the disease. The hospital records of 185 TBM children that presented to the Pediatric Clinics of Dicle University Hospital were retrospectively evaluated. The age, gender, family history of tuberculosis, result of Mantoux skin test, status of BCG vaccination, stage of TBM at hospitalization, and clinical, laboratory and radiological features were recorded. Clinical staging of TBM was defined as follows: Stage I, no focal neurological findings and Glasgow Coma Scale (GCS) score 15; Stage II, GCS 15 presenting with focal neurological deficit or all the patients with GCS 10-14; Stage III, all the patients with GCS < 10. Relationships between results and stages of TBM were investigated. The mean age of the patients was 53.5 ± 44.9 months (4 months-18 years). 121 (65.4 %) of the patients were male and 64 (34.6 %) female. Family history of tuberculosis was defined in 62 (33.5 %) patients. Forty five (24.3 %) children had BCG vaccination scar. Mantoux skin test was interpreted as positive in 35 (18.9 %) patients. Sixty-eight (36.8 %) children were at stage I TBM, 57 (30.8 %) at stage II and 60 (32.4 %) were at stage III on admission. Mean duration of hospitalization was 23.9 ± 14.1 days. Totally, 90 patients (48.6 %) had abnormal chest X-ray findings (parenchymal infiltration in 46 (24.9 %), mediastinal lymphadenopathy in 36 (19.5 %), miliary opacities in 25 (13.5 %), pleural effusion in 2 (1.1 %), and atelectasis in 2 (1.1 %) patients). One hundred sixty seven (90.3 %) patients had hydrocephalus in cranial computerized tomography. There were 24 (13.0 %) patients with positive culture for Mycobacterium tuberculosis and 3 (1.6 %) patients with positive acid-fast bacilli in cerebrospinal fluid. Overall mortality rate was 24 (13.0 %). Among the findings; patients at Stage III had less frequent positive chest X-ray abnormality, miliary opacities and BCG vaccination scar when compared with patients at Stage I and II (p = 0,005; p = 0,007, p = 0.020, respectively). Children with TBM and positive chest X-ray findings at hospital admission were more frequently diagnosed at Stage I, and BCG vaccination might be protective from the Stage III of the disease.


In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinoline derivatives.
The in vitro antimicrobial activity of ciprofloxacin (Bay o 9867) was compared with those of the other new fluorated piperazinyl-substituted quinoline derivatives: norfloxacin, ofloxacin, and pefloxacin, as well as with those of the earlier analogs, nalidixic acid and oxolinic acid. Virtually no resistance against the new fluorated piperazinyl-substituted quinoline derivatives was observed. As a rule, ciprofloxacin was about four times more active in vitro than the other new fluorated piperazinyl-substituted quinoline derivatives. The antibacterial spectrum of the new fluorated piperazinyl-substituted quinoline derivatives included, among other susceptible species, Pseudomonas aeruginosa, Streptococcus faecalis, Staphylococcus spp., and members of the family Enterobacteriaceae. In the case of ciprofloxacin, ofloxacin, and perfloxacin, anaerobes were included in the antibacterial spectrum as well. There was no cross resistance between the earlier analogs and the new fluorated piperazinyl-substituted quinoline derivatives. Regression analysis of MIC pairs for individual strains illustrated almost mathematical correlation between the antimicrobial activities of the quinoline derivatives.


[Retrospective DOSAK study of oral cavity carcinomas. Results and consequences].
In a multicentric, retrospective observational study on carcinomas of the oral cavity including the lips and the oropharynx a data material of 1021 patients has been analyzed. The specific goals of this study were: Review of existing proposals for classification; Analysis of prognostically relevant factors of the tumor disease; Construction of a prognostic index for the determination of individual and collective prognoses. The following results were gained: None of the TNM-classifications of oral cavity carcinomas does the necessary criteria justice not even approximately. The multivariate analyses of prognostically relevant factors were performed with and without taking therapeutical factors into account. The results unequivocally show that reliable prognoses are only possible under consideration of various treatment modalities. This led to the construction of the treatment-dependent prognostic index TPI, which will be eligible for the use within the clinical-therapeutical cancer research and within the clinical practice.


Ethics and policy in embryonic stem cell research.
Embryonic stem cells, which have the potential to save many lives, must be recovered from aborted fetuses or live embyros. Although tissue from aborted fetuses can be used without moral complicity in the underlying abortion, obtaining stem cells from embryos necessarily kills them, thus raising difficult questions about the use of embryonic human material to save others. This article draws on previous controversies over embryo research and distinctions between intrinsic and symbolic moral status to analyze these issues. It argues that stem cell research with spare embryos produced during infertility treatment, or even embryos created specifically for research or therapeutic purposes, is ethically acceptable and should receive federal funding.


Seroprevalence, spatial distribution and risk factors associated with Toxoplasma gondii infection among cattle in a quilombola community in the Brazilian cerrado.
Little is known about Toxoplasma gondii infection among cattle living in the Cerrado (Brazilian savanna) biome in Brazil. In particular, there is no epidemiological data relating to infection in quilombo lands, i.e. areas settled by Afro-descendants of escaped slaves. The aim of this study was to determine the prevalence, spatial distribution and risk factors associated with T. gondii infection among cattle in the Kalunga quilombo, in the Cerrado biome. Blood samples were collected from 1533 cattle for antibody detection using the indirect fluorescence antibody test (IFAT). The study area was subdivided into five macroregions to determine the spatial distribution of infection. An objective questionnaire was applied to the cattle owners to evaluate risk factors, which were analyzed using univariate analysis and logistic regression. The prevalence of T. gondii infection among cattle was 8.93% (137/1533), and antibodies were found in 49.6% of the herds (66/133), in all macroregions. The risk factors associated with T. gondii infection in cattle were the following: number of animals in the herd (OR: 30.56), purchase of cattle (OR: 2.57), age group (OR: 1.95) and average annual temperature (OR: 1.77). Thus, the occurrence rate, spatial distribution and risk factors associated with T. gondii infection among cattle in the Kalunga quilombola community are documented here, for the first time.


Cost of Healthcare Associated With Deep Vein Thrombosis in Patients Treated With Warfarin in Turkey: 2010-2013 Database Analysis of a Tertiary Care Center.
To evaluate the cost of healthcare with respect to the quality of anticoagulation in patients with deep vein thrombosis (DVT) treated with warfarin in daily practice via the database analysis of a tertiary care center in the period 2010 to 2013. Of 258 307 records in total, 42 582 unique patients with DVT and 32 012 patients with international normalized ratio (INR) measurements were included. Overall, 6720 unique patients with DVT diagnosis and one or more INR measurements were identified, and the records of 4377 out of 6720 unique patients were validated and included in the analysis data set. The cost analysis was based on direct medical costs from the payer's perspective. Cost items were related to healthcare resource utilization (inpatient and outpatient services) during the study period, which provided a basis for calculation of per-patient, outpatient, inpatient, and total direct medical costs. Mean outpatient, inpatient, and total hospital admission costs were $578, $2195, and $2785, respectively, for patients with time in the therapeutic range of 70% or more, whereas the same costs were $571, $2163, and $3192, respectively, for patients with time in the therapeutic range of less than 70%. Our findings for a retrospective cohort of patients with DVT undergoing warfarin therapy reveal that patients spent 70% or more, as opposed to less than 70%, of follow-up time within the therapeutic INR range and that outpatient care, as opposed to inpatient care, was associated with lower healthcare costs. Given the significant contribution that hospital stay makes to the cost burden of DVT, our findings also highlight the association between poor warfarin anticoagulant control and increased hospitalization costs.


[Active management of the third stage of labor: Three schemes of oxytocin: randomised clinical trial].
To compare the effectiveness of intramuscular oxytocin against intravenous oxytocin against intravenous traditional oxytocin infusion, in the active management of the third period of the delayed impingement labor work and controlled cord traction. Randomized controlled blinded clinical trial. In women age 14 to 40 with full term pregnancy, childbirth attended by ISSSTE's Regional Hospital "Gral. Ignacio Zaragoza", in the period from August to December 2015. 152 deliveries were attended, from which 66 fulfill with selection criteria. Group 1 = 22 patients, group 2 = 21 patients and Group 3 = 23 patients. The total age average was 26.92 + 5.8. For blood volume, statistical differences were significant among the three groups (p = 0.000). Adverse reactions were presented in 1 .5%, without difference between the groups. (P = 0.337). The differences in hemoglobin values and final and initial hematocrit presented differences with statistical significance (p = 0.000 for both). Nonetheless, the differences obtained in the analysis of the diverse variables among the three types of treatment, the three schemes are effective on the obstetrical hemorrhage prevention.