The influence of childhood abuse, adult life events, and affective temperaments on the well-being of the general, nonclinical adult population.
Previous studies have shown the effects of childhood abuse, life events, and temperaments on well-being (positive affect) and ill-being (negative affect). We hypothesized that childhood abuse, affective temperaments, and adult life events interact with one another and influence positive and negative affects in the general adult population and tested this hypothesis using structural equation modeling. A total of 415 participants from the general, nonclinical adult population were studied using the following self-administered questionnaires: the Subjective Well-Being Inventory (SUBI); Life Experiences Survey (LES); Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A); and the Child Abuse and Trauma Scale (CATS). The data were analyzed with single and multiple regression analyses and structural equation modeling (Mplus). Childhood abuse indirectly predicted the worsening of positive and negative affects through cyclothymic, anxious, and irritable temperaments as measured by the TEMPS-A in the structural equation model. The cyclothymic, anxious, and irritable temperaments directly worsened the positive and negative affects and the negative appraisal of life events that occurred during the past year, while the hyperthymic temperament had the opposite effects. The subjects of this study were nonclinical volunteers. The findings might not be generalizable to psychiatric patients. This study demonstrated that childhood abuse, particularly neglect, indirectly worsened the well-being of individuals through cyclothymic, anxious, and irritable affective temperaments. An important "mediator" role of affective temperaments in the effect of childhood abuse on well-being was suggested.


A Learning Framework for n-Bit Quantized Neural Networks Toward FPGAs.
The quantized neural network (QNN) is an efficient approach for network compression and can be widely used in the implementation of field-programmable gate arrays (FPGAs). This article proposes a novel learning framework for n -bit QNNs, whose weights are constrained to the power of two. To solve the gradient vanishing problem, we propose a reconstructed gradient function for QNNs in the back-propagation algorithm that can directly get the real gradient rather than estimating an approximate gradient of the expected loss. We also propose a novel QNN structure named n -BQ-NN, which uses shift operation to replace the multiply operation and is more suitable for the inference on FPGAs. Furthermore, we also design a shift vector processing element (SVPE) array to replace all 16-bit multiplications with SHIFT operations in convolution operation on FPGAs. We also carry out comparable experiments to evaluate our framework. The experimental results show that the quantized models of ResNet, DenseNet, and AlexNet through our learning framework can achieve almost the same accuracies with the original full-precision models. Moreover, when using our learning framework to train our n -BQ-NN from scratch, it can achieve state-of-the-art results compared with typical low-precision QNNs. Experiments on Xilinx ZCU102 platform show that our n -BQ-NN with our SVPE can execute 2.9 times faster than that with the vector processing element (VPE) in inference. As the SHIFT operation in our SVPE array will not consume digital signal processing (DSP) resources on FPGAs, the experiments have shown that the use of SVPE array also reduces average energy consumption to 68.7% of the VPE array with 16 bit.


A qualitative study comparing commercial and health service weight loss groups, classes and clubs.
Group-based interventions for weight loss are popular; however, little is known about how health service groups compare with the commercial sector, from either the participant or the group leader perspective. Currently, health professionals have little guidance on how to deliver effective group interventions. The present study aimed to compare and contrast leaders' and attendees' experiences of health service and commercial weight loss groups, through in-depth interviews and group observations. Purposive sampling, guided by a sampling frame, was employed to identify diverse groups operating in Scotland with differing content, structures and style. Data collection and analysis took place concurrently in accordance with a grounded theory approach. Thirteen semi-structured group observations and in-depth audio-recorded interviews with 11 leaders and 22 attendees were conducted. Identification of themes and the construction of matrices to identify data patterns were guided by the Framework Method for qualitative analysis. Compared to commercial groups, health service 'groups' or 'classes' tended to offer smaller periodic fixed term groups, involving gatekeeper referral systems. Commercial organisations provide a fixed branded package, for 'club' or 'class' members, and most commercial leaders share personal experiences of losing weight. Health service leaders had less opportunity for supervision, peer support or specific training in how to run their groups compared to commercial leaders. Commercial and health service groups differ in access; attendee and leader autonomy; engagement in group processes; and approaches to leadership and training, which could influence weight loss outcomes. Health service groups can provide different group content and experiences, particularly for those with chronic diseases and for populations less likely to attend commercial groups, such as men.


Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study.
To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and, of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.


"Spontaneous" differentiation of skeletal myoblasts is dependent upon autocrine secretion of insulin-like growth factor-II.
Differentiation of muscle cells to form postmitotic myotubes is usually viewed as being negatively controlled by medium components, sometimes designated "mitogens." However, we have found that a family of mitogenic agents, the insulin-like growth factors (IGFs), are potent stimulators of differentiation in myoblasts which act by inducing expression of the myogenin gene. We show here that this action of the IGFs occurs even when these growth factors are not added to the cell medium; upon transfer to low-serum "differentiation medium," myoblasts begin active expression of the IGF-II gene, at both the mRNA and protein levels. Furthermore, autocrine secretion of IGF-II is essential for the process of terminal differentiation of the cells. These conclusions are based upon four lines of evidence. (1) The rate of spontaneous differentiation in several sublines of myogenic cells correlates with their level of expression of IGF-II. (2) C2 and Sol 8 cells, which secrete high levels of IGF-II, are relatively insensitive to exogenous IGFs, in contrast to L6 lines, which exhibit lower levels of IGF-II gene expression. (3) An antisense oligodeoxyribonucleotide complementary to the first five codons of IGF-II inhibits myogenic differentiation in the absence but not in the presence of exogenous IGF-II. (4) Spontaneous differentiation in response to autocrine IGF-II involves the same mechanism that occurs in cells stimulated by the IGFs, i.e. elevation of expression of the myogenin gene.


"Drug mules" as a radiological challenge: sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox.
The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox(®)) in the detection of internal cocaine containers. Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16-45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT=35, nDR=70, nLSDR=30. An overall calculation of all "drug mules" and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.


Identification of targets of tumor suppressor microRNA-34a using a reporter library system.
miRNAs play critical roles in various biological processes by targeting specific mRNAs. Current approaches to identifying miRNA targets are insufficient for elucidation of a miRNA regulatory network. Here, we created a cell-based screening system using a luciferase reporter library composed of 4,891 full-length cDNAs, each of which was integrated into the 3' UTR of a luciferase gene. Using this reporter library system, we conducted a screening for targets of miR-34a, a tumor-suppressor miRNA. We identified both previously characterized and previously uncharacterized targets. miR-34a overexpression in MDA-MB-231 breast cancer cells repressed the expression of these previously unrecognized targets. Among these targets, GFRA3 is crucial for MDA-MB-231 cell growth, and its expression correlated with the overall survival of patients with breast cancer. Furthermore, GFRA3 was found to be directly regulated by miR-34a via its coding region. These data show that this system is useful for elucidating miRNA functions and networks.


MimoSA: a system for minimotif annotation.
Minimotifs are short peptide sequences within one protein, which are recognized by other proteins or molecules. While there are now several minimotif databases, they are incomplete. There are reports of many minimotifs in the primary literature, which have yet to be annotated, while entirely novel minimotifs continue to be published on a weekly basis. Our recently proposed function and sequence syntax for minimotifs enables us to build a general tool that will facilitate structured annotation and management of minimotif data from the biomedical literature. We have built the MimoSA application for minimotif annotation. The application supports management of the Minimotif Miner database, literature tracking, and annotation of new minimotifs. MimoSA enables the visualization, organization, selection and editing functions of minimotifs and their attributes in the MnM database. For the literature components, Mimosa provides paper status tracking and scoring of papers for annotation through a freely available machine learning approach, which is based on word correlation. The paper scoring algorithm is also available as a separate program, TextMine. Form-driven annotation of minimotif attributes enables entry of new minimotifs into the MnM database. Several supporting features increase the efficiency of annotation. The layered architecture of MimoSA allows for extensibility by separating the functions of paper scoring, minimotif visualization, and database management. MimoSA is readily adaptable to other annotation efforts that manually curate literature into a MySQL database. MimoSA is an extensible application that facilitates minimotif annotation and integrates with the Minimotif Miner database. We have built MimoSA as an application that integrates dynamic abstract scoring with a high performance relational model of minimotif syntax. MimoSA's TextMine, an efficient paper-scoring algorithm, can be used to dynamically rank papers with respect to context.


Carotid Artery Angioplasty and Stenting as a First-choice Revascularization Therapy for Cervical Carotid Artery Stenosis.
We examined the patients with cervical carotid artery stenosis (> 70%) treated by carotid artery angioplasty and stenting (CAS) as a firstchoice direct revascularization therapy. The patients consisted of 45 men and seven women; their mean age was 70.4 years (range, 54-84 yr), with 60 cervical carotid stenosis (39 symptomatic and 21 asymptomatic). Sixty procedures resulted in successful stent deployment in 55 cases, percutaneous transluminal angioplasty (PTA) only without stenting in three, and failed angioplasty due to inaccessibility in two. Morbidity was seen in three cases associated with thromboembolic complication. Instent restenosis was observed in one case, which was successfully treated with subsequent PTA. CAS seems reasonable treatment for cervical carotid artery stenosis, although further accumulation of the cases will be needed to evaluate the efficacy between CAS and carotid endarterectomy.


Clinical and neurocognitive features of the post Lyme syndrome.
To evaluate neurocognitive impairment in patients with persistent arthralgia, fatigue, and subjective memory loss in patients after Lyme disease (post-Lyme syndrome, PLS). We compared the clinical, neurocognitive, and psychological features of 23 patients with PLS to 23 age, sex, and education matched recovered patients (REC). All met Centers for Disease Control criteria for Lyme disease, were ELISA positive at onset of Lyme disease and were previously treated with standard antibiotic regimens. Of the patients with PLS, 7 (30%) had fibromyalgia (FM), 3 (13%) had chronic fatigue syndrome, and 10 (43%) had similar but milder symptoms but did not meet the criteria for either. 22 of 23 patients with PLS complained of decreased memory or concentration problems. Patients with PLS had significantly lower scores on the attention/concentration scale (p = 0.012) of the Wechsler Memory Scale-Revised (WMS-R), indicating lowered attention/concentration. 52% of patients with PLS and 35% in the REC group had significantly lower (p < 0.05) WMS-R verbal memory scores than visual memory scores. The PLS group had subjectively more problems with sleep and mood changes and higher scores on several scales of Symptom Check List 90-R (p < 0.01), indicating greater physical distress. Beck Depression Inventory scores were also higher for the PLS than the REC group (p < 0.005), but were within the normal range. Despite antibiotic treatment, a sequelae of Lyme disease may be a PLS characterized by persistent arthralgia, fatigue, and neurocognitive impairment that is probably induced by Lyme disease.


Difficult airway management patterns among attending anaesthetists practising in Israel.
In recent years, a large number of airway devices have been introduced into clinical practice as adjuncts to the management of the difficult airway. The purpose of this study was to evaluate the practices of Israeli anaesthetists in specific clinical situations and their familiarity with the use of a variety of airway devices and techniques. A survey developed in our institution was sent to 300 attending anaesthetists representing all board-certified anaesthetists practising in Israel. Of the 153 respondents, 75% belonged to university hospitals. Ninety-six percent were skilled with laryngeal mask airways and 73% with fibreoptics. Seventy percent preferred regional anaesthesia with anticipated difficult intubation, continuation of anaesthesia with a laryngeal mask with failed intubation and a laryngeal mask for impossible mask ventilation. For the airway scenarios, awake fibreoptic, awake direct laryngoscopy, intubation under inhalation anaesthesia and tracheostomy were shared equally. There is a high degree of adherence by Israeli anaesthetists to the American Society of Anesthesiologists' difficult airway algorithm. Current airway management practice patterns in Israel are presented.


A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014-2020).
Heart failure presents a growing clinical and economic burden in the USA. Robust cost data on the burden of illness are critical to inform economic evaluations of new therapeutic interventions. This systematic literature review of heart failure-related costs in the USA aimed to assess the quality of the published evidence and provide a narrative synthesis of current data. Four electronic databases (MEDLINE, EMBASE, EconLit, and the Centre for Reviews and Dissemination York Database, including the NHS Economic Evaluation Database and Health Technology Assessment Database) were searched for journal articles published between January 2014 and March 2020. The review, registered with PROSPERO (CRD42019134201), was restricted to cost-of-illness studies in adults with heart failure events in the USA. Eighty-seven studies were included, 41 of which allowed a comparison of cost estimates across studies. The annual median total medical costs for heart failure care were estimated at $24,383 per patient, with heart failure-specific hospitalizations driving costs (median $15,879 per patient). Analyses of subgroups revealed that heart failure-related costs are highly sensitive to individual patient characteristics (such as the presence of comorbidities and age) with large variations even within a subgroup. Additionally, differences in study design and a lack of standardized reporting limited the ability to compare cost estimates. The finding that costs are higher for patients with heart failure with reduced ejection fraction compared with patients with preserved ejection fraction highlights the need for differentiating among different heart failure types. The review underpins the conclusion drawn in earlier reviews, namely that hospitalization costs are the key driver of heart failure-related costs. Analyses of subgroups provide a clearer understanding of sources of heterogeneity in cost data. While current cost estimates provide useful indications of economic burden, understanding the nuances of the data is critical to support its application.


Polymorphism in some nearctic halictine bees.
Average difference in size between queens and workers of four social Halictinae common to southern Ontario ranges from 6 percent in Augochlorella striata (Prov.) to 15 percent in Evylaeus cinctipes (Prov.). Spring larvae receive. provisions averaging 33.9 milligrams and become small workers; summer larvae consume on average 61.7 milligrams and develop into large queens and males.


Developing and assessing a kin keeping scale with application to identifying central influencers in African American family networks.
Promoting family communication about inherited disease risk is an arena in which family systems theory is highly relevant. One family systems' construct that can support promotion of family communication regarding inherited disease risk is the notion of "kin keeping." However, kin keeping and whether it might be capitalized on to encourage family communication about inherited risk has been understudied. The goal of this report was to propose a broadened conceptualization of kin keeping that distinguishes between a structural functional perspective (role conceptualization) and transitional behaviors (skill conceptualization), and to develop and evaluate a scale that would enable this assertion to be tested among a sample of African American community health workers. We developed a scale using four steps: item development using concept analysis and content validity, scale development among a national sample (n = 312), scale evaluation using exploratory factor analysis (n = 52), and scale reduction. We then posed suppositions of associations that would indicate whether the developed kin keeping measure was assessing a specific family role or set of behaviors. Our results included the development of the first quantitative measure of kin keeping (9- and 15-item scales). Model fit for 9-item scale (CFI = 0.97, AFGI = 0.89, RMSEA = 0.09, SMRM = 0.06) and model fit for 15-item scale (CFI = 0.97, AFGI = 0.89, RMSEA = 0.06, SMRM = 0.05). These findings allow us to move toward more rigorous research about the role of kin keeping on information sharing and health decision making. Results also suggest that, contrary to the historical structural functional conceptualization of kin keeping as a role, kin keeping might also be conceptualized as a behavior or set of modifiable behaviors. Ultimately, the kin keeping scale could be used to operationalize kin keeping in various theoretical models and frameworks, guide intervention development to encourage or train for kin keeping behaviors, and test assumptions of whether families vary in the density of kin keeping.


[Investigation of the Contribution of Autoantibodies to Clinical Diagnosis in Liver Pathologies and the Identification of Accompanying Autoimmune Diseases].
Autoantibodies are frequently detected in the presence of autoimmune liver diseases (ALD) [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)] and are widely used to classify the disease clinically. The aim of this study was to investigate the contribution of autoantibodies for the diagnosis of ALD and the identification of other accompanying systemic autoimmune rheumatic diseases (SARD). In addition, it was aimed to compare the results of indirect immunofluorescence (IIF) antinuclear antibody (ANA) patterns and extractable nuclear antigen (ENA) antibodies. A total of 593 patients, including 544 patients with high liver function tests from general surgery/gastroenterology clinics and 49 patients referred from internal medicine/rheumatology clinics to investigate ALD, were included in the study. HBsAg and anti-HCV test results of the patients were found to be negative. ANA, anti-mitochondrial antibody (AMA)/anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibody (ASMA), antineutrophil cytoplasmic antibody (ANCA) assays were performed by indirect immunofluorescence method (IIF) (Euroimmune AG, Luebeck, Germany). Extractable nuclear antigen (ENA) (nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, dsDNA, nucleosome, histone, ribosomal P-protein, AMA-M2, Ro-52, PM-Scl, CENP-B, PCNA, DFS70) and liver profiles [soluble liver antigen\liver pancreas antigen (SLA/LP), liver cytosolic antigen1(LC-1), LKM-1, anti-mitochondrial antibody M2(AMA-M2)] (Euroimmune AG, Luebeck, Germany) were detected by immunoblot (IB) method. Demographic characteristics, clinical data, presence of systemic autoimmune rheumatic diseases (SARD), radiological and laboratory findings were determined from the medical records. Autoantibody tests were found to be negative in 461 (77.7%) of 593 patients (mean age= 53.3 ± 15.6, age range= 18-90), and were positive in 132 (22.3%) (86.4% female) of the patients. Of the patients with positive autoantibodies, 60.6% (80/132) were diagnosed as PBS and 1.5% (2/132) were diagnosed as AIH (positive anti-LC-1 and anti-LKM1 antibodies). Fourteen of the patients (10.6%) with centromere, nuclear membrane (NM), multiple nuclear dot (MND) staining patterns and elevated liver enzymes could not be diagnosed as a specific disease and were followed up. PBS (13/30) was detected in approximately half of the patients diagnosed with SARD. The most common accompanying SARD in PBC patients was Sjögren's syndrome (SS) (7.5%, 6/80), followed by rheumatoid arthritis (RA) (5.0%, 4/80), scleroderma (2.5%, 2/80), and systemic lupus erythematosus (SLE) (1.3%, 1/80) respectively. The most common pattern was the AMA staining pattern (34.8%, 46/132) among the autoantibody positive patients. AMA and ANA staining patterns were detected together in 31.1% (41/132) of the patients. In the ENA profile results of these patients, the most common profile detected was anti-Ro-52 (65.9%, 27/41), followed by anti-SSA (34.1%, 14/41), anti-SSB (22.0%, 9/41) and anti-CENP-B (12.2%, 5/41) autoantibodies , respectively. ANA patterns were detected in 32.6% (43/132) of the patients (NM 9.1%, centromere 9.1%, MND 6.8%, respectively). In our study, 87.5% (70/80) of the patients diagnosed as PBS were found to have AMA positivity and 12.5% (10/80) of them had ANA positivity (such as NM, CNN, centromere). The characteristics, laboratory and radiological findings of the patients with isolated AMA positivity alone (Group 1) and patients with multiple patterns/autoantibodies (Group 2) were compared. In patients with multiple patterns/autoantibodies (Group 2), the presence of cirrhosis and liver heterogeneity were found to be higher than Group 1 (p= 0.049). ALD associated autoantibodies can be detected before years from the clinical disease. ALD may be associated with various SARD. Detection of ALD-related autoantibodies in patients diagnosed with SARD can provide early diagnosis of these patients. These autoantibodies guide both diagnosis and prognosis as in PBC. Collaboration between the laboratory specialist and the clinician is critical in the diagnosis, management and early recognition of these patients before clinical disease.


The inference of speech perception in the phonologically disordered child. Part I: A rationale, some criteria, the conventional tests.
This paper considers the rationale and presents some criteria for assessing the speech perception of children with disorders at the phonological level of language. An examination of conventional test procedures suggests that none is useful in identifying clinically relevant perceptual disorders. However, readers are encouraged to inspect Part II (Locke, 1980), which describes procedures with more clinical promise.


A pilot, 8-week, placebo lead-in trial of quetiapine extended release for depression in midlife women: impact on mood and menopause-related symptoms.
Perimenopausal and early postmenopausal women have shown an increased risk for developing depression (new onset or recurrent); concomitant vasomotor and other menopause-related complaints significantly affect quality of life and overall functioning. This study examined the effects of quetiapine extended release (XR) in midlife women with major depressive disorder who also reported significant menopause-related symptoms. Forty eligible women with major depressive disorder entered a 2-week, placebo lead-in phase, followed by an 8-week open trial with quetiapine XR, flexible dose, 150-300 mg/d. The primary outcome measure (depressive symptoms) was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Other measures included menopause symptoms (Greene Climacteric Scale total scores and subscores) and the impact of hot flashes on functioning (Hot Flash-Related Daily Interference Scale). Weight, cholesterol, triglycerides, and glucose levels were monitored. Data from 24 subjects (modified intent-to-treat, last observation carried forward; quetiapine XR mean dose, 191 [SD, 55] mg/d) showed improvement in depressive and menopause-related symptoms, that is, reduction in MADRS, GCS, and Hot Flash-Related Daily Interference Scale scores (P < 0.01 for all comparisons). Seventeen subjects were considered responders (>50% reduction in MADRS scores); 15 achieved remission (MADRS<10). Main adverse effects included drowsiness and dry mouth. Based on these preliminary results, quetiapine XR should be further examined in larger, controlled trials for the management of depressed, symptomatic midlife women.


[Application of DNA extraction kit, 'GM quicker' for detection of genetically modified soybeans].
Several DNA extraction methods have been officially introduced to detect genetically modified soybeans, but the choice of DNA extraction kits depend on the nature of the samples, such as grains or processed foods. To overcome this disadvantage, we examined whether the GM quicker kit is available for both grains and processed foods. We compared GM quicker with four approved DNA extraction kits in respect of DNA purity, copy numbers of lectin gene, and working time. We found that the DNA quality of GM quicker was superior to that of the other kits for grains, and the procedure was faster. However, in the case of processed foods, GM quicker was not superior to the other kits. We therefore investigated an unapproved GM quicker 3 kit, which is available for DNA extraction from processed foods, such as tofu and boiled soybeans. The GM quicker 3 kit provided good DNA quality from both grains and processed foods, so we made a minor modification of the GM quicker-based protocol that was suitable for processed foods, using GM quicker and its reagents. The modified method enhanced the performance of GM quicker with processed foods. We believe that GM quicker with the modified protocol is an excellent tool to obtain high-quality DNA from grains and processed foods for detection of genetically modified soybeans.


Pneumocystis carinii pneumonia masquerading as tuberculosis.
Recent laboratory studies indicate that genetic diversity exists in human strains of Pneumocystis carinii. Structural and functional variability in infecting strains could result in differences in host-parasite interactions and the natural history of P carinii pneumonia. We report 5 unusual cases in which the clinical presentation mimicked tuberculosis. All patients were cared for at a university-based public hospital clinic in Los Angeles, Calif, during a 2-year period. These patients were chronically ill, had lost weight, and each had cavities or cystic spaces as the primary radiographic findings. None were receiving aerosol pentamidine and only one had a history of smoking. Four patients were initially treated for tuberculosis and the fifth for disseminated Mycobacterium avium complex. Pneumocystis carinii was the only pathogen identified in each case. The unusual clinical presentations delayed the diagnosis of P carinii in all 5 cases. Practitioners must be aware of the variable presentations of P carinii pneumonia.


Negative functional connectivity and its dependence on the shortest path length of positive network in the resting-state human brain.
It is suggested that structurally segregated and functionally specialized brain regions are mediated by synchrony over large-scale networks in order to provide the formation of dynamic links and integration functions. The existence of negative synchrony, or negative functional connectivity (NFC), however, has been a subject of debate in terms of its origin, interpretation, relationship with structural connectivity, and possible neurophysiological function. The present study, which incorporated 20 cognitively healthy elderly human subjects, focused on testing the hypothesis that NFC significantly correlates with the shortest path length (SPL) in the human brain network. Our theoretical calculation, simulated data, and human study results support this hypothesis. In the human study, we find that (1) the percentage of NFC connections among all connections between brain regions significantly correlates with spatial Euclidian distance; (2) the strength of the NFC between the right amygdala and the left dorsolateral prefrontal cortex is significantly correlated with the SPL across the 20 human subjects; (3) such a significant relationship between the NFC and SPL exists in all the NFC connections in the whole brain; and (4) the correlations between the NFC and SPL also are frequency bandwidth dependent. These results suggest that an accumulated phased delay gives rise to the NFC, along the shortest path in the large-scale brain functional network. It is suggested that our study can be extended to examine a variety of neurological diseases and psychiatric disorders by measuring the changes of SPL and functional reorganization in the brain.


Genetic analysis of developmental mechanisms in hydra. XIX. Stimulation of regeneration by injury in the regeneration-deficient mutant strain, reg-16.
A mutant strain of Hydra magnipapillata, reg-16, has a very low regenerative capacity. After head removal, it usually restores 10-20% of the original number of tentacles in 7 days. A procedure was found to markedly improve tentacle regeneration in this strain. The closed wound located at the apical regenerating tip of the decapitated polyp was gently reopened using a pair of forceps. Reg-16 polyps treated in this way at 24 and 48 h after head removal restored nearly all of the original number of tentacles in 7 days. A lateral tissue transplantation procedure was employed to examine the effect of wound reopening on the morphogenetic potential of decapitated reg-16 polyps. Wound reopening produced a significant increase in head activation level without producing a preceding decrease in head inhibition level. This and other observations suggest that the coupled activation-inhibition changes that normally occur after head removal from the wild-type hydra do not occur in this strain. Mechanisms responsible for the wound reopening effect and the absence of activation-inhibition coupling in the mutant strain reg-16 are discussed.


[Clamping of the thoracic aorta in a hypertensive patient with coronary disease. An indication of sodium nitroprusside (author's transl)].
In patients with cardiac failure, coronary disease or arterial hypertension, clamping of the aorta results in increased filling pressure of the left ventricle which may produce or increase subendocardial ischaemia with consequent aggravation of the ventricular insufficiency. And the higher the clamping the greater the risk. This vicious circle can be broken by sodium nitroprusside, which has potent and reversible vasodilator properties. The drug is indicated whenever the left ventricular filling pressure rises above 5 mmHg. These considerations are illustrated by the descriptions of a case where sodium nitroprusside ensured blood circulation in the lower limbs and intra-abdominal organs after clamping of the aorta above the coeliac artery in a high risk cardiac patient.


Profiling of pentose phosphate pathway intermediates in blood spots by tandem mass spectrometry: application to transaldolase deficiency.
Recently, several patients with abnormal polyol profiles in body fluids have been reported, but the origins of these polyols are unknown. We hypothesized that they are derived from sugar phosphate intermediates of the pentose phosphate pathway (PPP), and we developed a semiquantitative method for profiling of pentose phosphate pathway intermediates. Sugar phosphates in blood spots were simultaneously analyzed by liquid chromatography-tandem mass spectrometry using an ion-pair-loaded C(18) HPLC column. The tandem mass spectrometer was operated in the multiple-reaction monitoring mode. Enzymatically prepared D-[(13)C(6)]glucose 6-phosphate was used as internal standard. The method was used to study sugar phosphates abnormalities in a patient affected with a deficiency of transaldolase (TALDO1; EC 184.108.40.206). In control blood spots, dihydroxyacetone phosphate, pentulose 5-phosphates, pentose 5-phosphates, hexose 6-phosphates, and sedoheptulose 7-phosphate were detected. Detection limits ranged from approximately 100 to approximately 500 nmol/L. Glyceraldehyde 3-phosphate and erythrose 4-phosphate were undetectable. Intra- and interassay imprecision (CVs) were 10-17% and 12-21%, respectively. In blood from the TALDO1-deficient patient, sedoheptulose 7-phosphate was increased. The new method allows investigation of patients in whom a defect in the PPP is suspected. Measurements of sugar phosphate intermediates of the PPP may provide new insights into metabolic defects underlying the accumulating polyols.


Phenotype and regulation of persistent intracerebral T cells in murine Toxoplasma encephalitis.
Toxoplasma gondii is a parasite causing asymptomatic, persistent encephalitis. Protective CD4 and CD8 T cells are recruited to and accumulate in the brain in acute Toxoplasma encephalitis (TE), with slowly decreasing numbers in chronic TE. It is unclear how the size of the intracerebral T cell pool is regulated. Conceivably, permanent recruitment, proliferation, and apoptosis may be involved. We observed that in murine TE recruitment of T cells to the brain was terminated in chronic TE. In vivo 5-bromo-2'-deoxyuridine incorporation and in vitro T cell proliferation experiments revealed that intracerebral T cells did not proliferate, which was explained by the expression of the cell cycle inhibitors p21(Waf/cip1) and p27(Kip1) and the inhibitory activity of intracerebral F4/80(+) cells. TUNEL staining detected apoptotic T cells at low frequency corresponding to an increased expression of the anti-apoptotic molecules Bcl-2 and Bcl-x(L) and a reduced expression of the pro-apoptotic molecules Bad, Bax, and Fas ligand in CD4 and CD8 T cells. During progression from acute to chronic TE, both CD4 and CD8 T cells down-regulated CD45RB expression and expressed a differential pattern of cytokines. From these experiments it is concluded that the number of intracerebral T cells increases by recruitment of T cells during acute infection, whereas proliferation of intracerebral T cells does not play a role. In chronic TE, T cell recruitment is terminated, the phenotype of intracerebral T cells changes, and their number is gradually downsized by low level apoptosis, which, however, does not completely resolve the T cell infiltrates.


Antimicrobial therapy for rams with Brucella ovis infection of the urogenital tract.
Rams shedding Brucella ovis in semen but without palpable abnormalities of the epididymides were treated with long-acting oxytetracycline for 15 days and dihydrostreptomycin for 7 days (n = 9) or conventional oxytetracycline and dihydrostreptomycin (n = 9) for 7 days. Nine rams were not treated. More treated rams were considered to have satisfactory breeding soundness examination results at posttreatment weeks 3, 7, 12, and 19. Nontreated rams continued to shed B ovis in semen. After treatment, B ovis was not recovered from 78% of rams given long-acting oxytetracycline and dihydrostreptomycin or from 89% of rams given conventional oxytetracycline and dihydrostreptomycin. At week 21, all rams were euthanatized, and specimens of the testes and epididymides were bacteriologically cultured for B ovis. Brucella ovis was not recovered from the testes of rams or from the epididymides from rams not shedding the organism in the semen. In one treated ram, B ovis was recovered from the semen but not from other tissues. All rams remained ELISA-positive, with the exception of 2 treated rams that ceased shedding B ovis in semen immediately after treatment was started; both these rams became ELISA-negative on the last examination at week 19.


[Anti-atherosclerotic properties of some components of food (a clinico-experimental study)].
Platelet lysosomal proteinase and phospholipase activity, cholesterol content in the blood serum and circulating immune complexes, as well as blood serum atherogenic potential were studied with the use of human aortal intima atherosclerotic cell culture in patients with postinfarction cardiosclerosis (males aged from 45 to 62 years), 1-3 h before and 2-6 h after a single intake of one of the following products (50 g): sunflower oil, butter, cod fat, glucose, fructose, starch, dried milk protein, or 22 g of soybean protein isolate 500 U. The total data obtained have evidenced that the soybean protein isolate produces hypolipidemic and hypocholesterolemic effects, as well as possesses pronounced anti-atherosclerotic properties.


Hormonal therapy in carcinoma of the kidney.
During the past 10 years we have studied 216 patients with renal cell carcinoma (RCC). After nephrectomy the patients were divided into two groups: one group received adjuvant acetate medroxyprogesterone therapy and the other formed our control group. The mean follow-up was 4.9 years. Survival was studied through univariate and multivariate analysis, according to Cox's multiple regression. To evaluate survival the following variables were taken into consideration: stage, grade, ploidy, sex, age, MAP therapy, Er, AR, PR receptors. The survival curves according to Kaplan and Meier were statistically significant for stage, grade, MAP therapy and DNA cellular content. The other variables were not statistically significant prognostic factors. Multivariate analysis demonstrated that only stage and MAP therapy are capable of influencing survival. A low stage has a better survival rate and in equivalent stages those who have received MAP live longer.


Effects of wrist-extension orthosis on shoulder and scapular muscle activities during simulated assembly tasks.
The purpose of this study was to observe changes in electromyographic activity appeared in shoulder and scapular muscles when one wears no wrist extension orthosis, short wrist extension orthosis and long wrist extension orthosis when performing two model assembling operations. The study subjects were 16 adults who use right hand and did not have any functional disorder on their wrist or the upper limbs without any orthopedic surgery. The study subjects were asked to do the two model assembling operations without wrist extension orthosis, with a short wrist extension orthosis and with a long wrist extension orthosis. As a result of repetitive assembling operation that requires shoulder movement, electromyographic activity in upper trapezius and serratus anterior increased significantly when the subjects wore the short and long wrist extension orthoses compared to none. When the subjects performed repetitive assembling operation that requires shoulder stability, electromyographic activity in upper trapezius, lower trapezius, serratus anterior, and anterior deltoid showed significant increase when they wore the short and long wrist extension orthoses compared to none. Especially, the upper trapezius showed significantly high electromyographic activity when they wore the long wrist extension orthosis compared to a short one.


Anion exchange dynamics in the capture of perchlorate by a cationic Ag-based MOF.
We report a detailed study of the host-guest interaction for a cationic metal-organic framework that can reversibly capture perchlorate. The structural transformation and flexibility of silver 4,4'-bipyridine nitrate (SBN) upon formation of silver 4,4'-bipyridine perchlorate (SBP) was evaluated by monitoring the anion exchange dynamics using a combination of powder X-ray diffraction (PXRD) with multinuclear 13C, 15N and 109Ag solid-state NMR spectra at different time intervals of the anion exchange. The structural transformation from SBN to SBP is complete within 70 minutes and was determined to take place by a solvent-mediated process. This pathway is confirmed by the morphological changes of the two crystalline materials observed by SEM. This key understanding may lead to application of this material towards perchlorate capture.


Lymphocyte response to phytohemagglutinin: intracellular volume and intracellular [K+].
The effect of phytohemagglutinin (PHA) on lymphocytes was examined with respect to free intracellular water volume and intracellular [K+]. At a cell concentration of 30 X 10(6) lymphocytes/ml in modified Hank's Buffered Salt Solution (HBSS) in the presence of 10% human AB serum, addition of PHA at 3 mg/ml resulted in a 24-27% decrease in free intracellular water space within 30 to 60 minutes and a return to control level after three hours. A larger change in intracellular water (44%) was observed under similar conditions in the absence of serum. The absolute intracellular K+ content did not change after PHA addition, but the cell water volume decrease arising from PHA addition resulted in a 29% increase in intracellular [K+] at 60 minutes. The decrease in lymphocyte water volume induced by PHA was also observed for concanavalin A which stimulates lymphocyte proliferation, but not for wheat germ lectin, an agglutinating agent which is not mitogenic. Thus, volume regulation may be closely associated with the mitogenicity of these compounds.


Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI.
Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is an emerging imaging modality that allows assessment of both ventilation and gas transfer. Most research to date has focused on non-malignant pulmonary diseases. However, the capability of evaluating the two primary physiological processes of the lung (ventilation and gas transfer) makes HP 129 Xe MRI a promising imaging modality in the management of patients with lung cancer.


Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.
Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.


Is UNAIDS 90-90-90 target a Dream or a Reality for Middle East and North Africa Region on Ending the AIDS Epidemic? A Review Study.
Middle East and North Africa (MENA) region is lagging far behind the global average to reach 90-90-90 targets. This study uses the UNAIDS 90-90-90 program to evaluate the HIV current situation in MENA countries, and understand the challenges that exist in the way of approaching the program goals. All articles and publications were searched based on the 90-90-90 program indexes among national and international data resources such as official national reports and online scientific databases such as PubMed, Medline, and Scopus up to December 2017. The data were categorized into four main stages: (1) estimated number of HIV-positive people (people living with HIV [PLWH]); (2) PLWH who know their status; (3) PLWH receiving antiretroviral therapy (ART); and (4) virally suppressed PLWH. A total of 41 papers were included in the study. 19 out of 24 MENA countries have met the inclusion criteria. The proportion of diagnosed people ranges from 6% in Pakistan to 76% in Algeria. The percentage of diagnosed people receiving ART ranges between 7% in Pakistan and 86% in Algeria. Viral suppression levels vary from 4% to 72% in Pakistan and Kuwait, respectively. Lack of appropriate surveillance systems, low access to HIV-care facilities along with complicated socioeconomic and geopolitical situation of the region have made it challenging for MENA countries to reach 90-90-90 goals by 2020. To achieve these goals, the foremost strategy is global effort to establish peace in this region and rebuild the infrastructure in the countries involved in war and to setup comprehensive surveillance systems in the majority of the MENA countries.


Cloning and expression of the mouse deoxyuridine triphosphate nucleotidohydrolase gene: differs from the rat enzyme in that it lacks nuclear receptor interacting LXXLL motif.
We have previously reported the cloning of rat deoxyuridine triphosphate nucleotidohydrolase (dUTPase) cDNA and demonstrated that the full-length protein as well as the N-terminal 62-amino acid peptide interacts with peroxisome proliferator-activated receptor alpha (PPARalpha). We now report the cloning of mouse dUTPase cDNA and show that it contains a 162-amino acid open reading frame, encoding a protein with a predicted Mr of 17,400 and differs from rat cDNA, which contains additional 43 amino acids at the N-terminal end. Unlike rat dUTPase, mouse dUTPase failed to bind PPARalpha. An evaluation of 205 amino acid containing rat dUTPase cDNA revealed that the N-terminal 43 extra amino acid segment contains an LXXLL signature motif, considered necessary and sufficient for the binding of several cofactors with nuclear receptors, and its absence in murine dUTPase possibly accounts for the differential binding of these enzymes to PPARalpha. In situ hybridization and immunohistochemical studies revealed that, in the adult mouse, dUTPase is expressed at high levels in proliferating cells of colonic mucosa, and of germinal epithelium in testis. At 9.5-day mouse embryonic development, dUTPase expression is predominantly in developing neural epithelium, and hepatic primordium, and in later developmental stages (11.5-, 13.5-, and 15.5-day embryo), the expression began to be localized to the liver, kidney, gut epithelium, thymus, granular layer of the cerebellum, and olfactory epithelium. We also show that the murine dUTPase gene comprises 6 exons and the 5'-flanking region of -1479 to -27, which exhibited high promoter activity, contains a typical TATA box and multiple cis-elements such as Sp-1, AP2, AP3, AP4, Ker1, RREB, and CREB binding sites. These observations suggest the existence of variants of dUTPase, some of which may influence nuclear receptor function during development and differentiation, in addition to catalyzing the hydrolysis of dUTP to dUMP.


Childhood vitiligo.
Vitiligo is a common skin disorder in which pigment is lost from the skin and adnexae. Half of all cases begin before the age of 20 years. Until recently, there was a paucity of published data regarding effective therapy of vitiligo. Current therapy is quite effective, and while many patients may not experience complete repigmentation, 50% to 75% repigmentation of vitiligo with recent onset routinely can be expected with available therapeutics.


Genetics and biology of Alzheimer's disease and frontotemporal lobar degeneration.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a presenile onset. The two major neuropathologic hallmarks of AD are extracellular Amyloid beta (Abeta) plaques and intracellular neurofibrillary tangles (NFTs). Conversely, in FTLD the deposition of tau has been observed in a number of cases, but in several brains there is no deposition of tau but instead a positivity for ubiquitin. In some families these diseases are inherited in an auto-somal dominant fashion. Genes responsible for familial AD include the Amyloid Precursor Protein (APP), Presenilin 1 (PS1) and Presenilin 2 (PS2). The majority of mutations in these genes are often associated with a very early onset (40-50 years of age). Regarding FTLD, the first mutations described are located in the Microtubule Associated Protein Tau gene (MAPT). Tau is a component of microtubules, which represent the internal support structures for the transport of nutrients, vesicles, mitochondria and chromosomes within the cell. Mutations in MAPT are associated with an early onset of the disease (40-50 years), and the clinical phenotype is consistent with frontotemporal lobar degeneration (FTD). Recently, mutations in a second gene, named progranulin (GRN), have been identified in some families with FTLD. Progranulin is expressed in neurons and microglia and displays anti-inflammatory properties. Nevertheless, it can be cleaved into granulins which, conversely, show inflammatory properties. The pathology associated with these mutations is most frequently characterized by the immunostaining of TAR DNA Binding Protein 43 (TDP-43), which is a transcription factor. The clinical phenotype associated with GRN mutations is highly heterogeneous, including FTD, Progressive Aphasia, Corticobasal Syndrome, and AD. Age at disease onset is variable, ranging from 45 to 85 years of age. The majority of cases of AD and FTLD are however sporadic, and likely several genetic and environmental factors contribute to their development. Concerning AD, it is known that the presence of the e4 allele of the Apolipoprotein E gene is a susceptibility factor, increasing the risk of about 4 fold. A number of additional genetic factors, including cytokines, chemokines, Nitric Oxide Synthases, contribute to the susceptibility for the disease. Some of them also influence the risk to develop FTLD. In this review, current knowledge on molecular mechanisms at the basis of AD and FTLD, as well as the role of genetics, will be presented and discussed.


Fever after rewarming: incidence of pyrexia in postcardiac arrest patients who have undergone mild therapeutic hypothermia.
Induction of mild therapeutic hypothermia (TH; temperature 32-34°C) has become standard of care in many hospitals for comatose survivors of cardiac arrest. Pyrexia, or fever, is known to be detrimental in patients with neurologic injuries such as stroke or trauma. The incidence of pyrexia in the postrewarming phase of TH is unknown. We attempted to determine the incidence of fever after TH and hypothesized that those patients who were febrile after rewarming would have worse clinical outcomes than those who maintained normothermia in the postrewarming period. Retrospective data analysis of survivors of out-of-hospital cardiac arrest (OHCA) over a period of 29 months (December 2007 to April 2010). OHCA, age >18, return of spontaneous circulation, and treatment with TH. traumatic arrest and pregnancy. Data collected included age, sex, neurologic outcome, mortality, and whether the patient developed fever (temperature > 100.4°F, 38°C) within 24 hours after being fully rewarmed to a normal core body temperature after TH. We used simple descriptive statistics and Fisher exact test to report our findings. A total of 149 patients were identified; of these, 82 (55%) underwent TH. The mean age of the TH cohort was 66 years, and 28 (31%) were female. In all, 54 patients survived for >24 hours after rewarming and were included in the analysis. Among the analyzed cohort, 28 (52%) of 54 developed fever within 24 hours after being rewarmed. Outcome measures included in-hospital mortality as well as neurologic outcome as defined by a dichotomized Cerebral Performance Category (CPC) score. When comparing neurologic outcomes between the groups, 16 (57%) of 28 in the postrewarming fever group had a poor outcome (CPC score 3-5), while 15 (58%) of 26 in the no-fever group had a favorable outcome (P = .62). In the fever group, 15 (52%) of 28 died, while in the no-fever group, 14 (54%) of 26 died (P = .62). Among a cohort of patients who underwent mild TH after OHCA, more than half of these patients developed pyrexia in the first 24 hours after rewarming. Although there were no significant differences in outcomes between febrile and nonfebrile patients identified in this study, these findings should be further evaluated in a larger cohort. Future investigations may be needed to determine whether postrewarming temperature management will improve the outcomes in this population.


[Infectious exacerbation of chronic obstructive pulmonary disease: prospects for high-dose levofloxacin therapy].
This open comparative randomized study of efficacy, safety, and pharmacoeconomic characteristics of hilifox-750 (750 mg daily for 5 days) and amoxiclav 2X (875/125 mg twice daily for 10 days) included 60 patients with chronic obstructive pulmonary disease (COPD). Duration of the study was 6 months. Medians of age and smoking index in the group treated with hilifox-750 were 63.5 yr (59, 67) and 30 packs/yr (15, 60) respectively. The treatment reduced cough, apnea, sputum volume and pyoptysis with comparative rates of normalization of body temperature and peripheral leukocyte counts in both groups. Helifox-750 promoted decrease in coughing and apnea within the first three days of therapy. 28 (93%) and 26 (87%) patients recovered by day 4 of helifox and amoxiclav therapy (F-test p = 0.67). Both drugs showed comparable bacteriological efficacy. They were not different in terms of side effect frequency that were mild, resolved spontaneously and did not require withdrawal of therapy. Helifox had advantages over amoxiclav in that it reduced duration of antibacterial therapy to 5 days and of temporary incapacity to 12 days (vs 14); moreover, it needs to be taken only once daily.


The Composition of Fatty Acids in Bee Pollen, Royal Jelly, Buckthorn Oil and Their Mixtures with Pollen Preserved for Storage.
Honey produced by A. mellifera contains minor components present in the nectar collected from plants. Various studies of honey components and all other bee products can be informative in assessing their quality. The aim of the present study was to determine the content and composition of fatty acids (FAs) in sea buckthorn oil (SBO), royal jelly (RJ) and bee pollen (BP) and the changes in FAs content in these products during storage. The diversity of FAs and the effect of storage time on FAs content was also evaluated for the prepared-for-preservation mixtures, which included the following samples: pollen mixed with honey at a ratio of 1:2 (w/w); sample BPH, a well; BPH + 1% (w/w) SBO; and BPH + 1% (w/w) SBO + 2% (w/w) RJ. Fresh bee-collected pollen and RJ were stored at -20 °C, whereas the conserved samples were stored at +4 °C in hermetically sealed jars. The data revealed that RJ demonstrated the highest diversity of fatty acids compared to BP and BP prepared for storage with honey along with SBO and RJ. Palmitic and stearic acids were found in the highest amounts out of the eight saturated fatty acids identified in the studied SBO and RJ. The amount of these fatty acids in RJ compared to SBO was 1.27 and 6.14 times higher, respectively. In total, twenty-two unsaturated fatty acids (USFA) were identified in RJ and fourteen were found in SBO. The SBO used in this study was found to be high in linoleic acid, resulting in an increased n-6 fatty acids ratio in the prepared samples. Essential fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) were found in RJ, as well as in BP and BP mixed with honey. These FAs were not identified in the samples prepared with SBO even in the sample supplemented with RJ. The highest decrease in docosadienoic fatty acid was found in the BPH sample compared to BP, while arachidonic acid mostly decreased in BPH + 1% SBO compared to the BPH + 1% (w/w) SBO + 2% (w/w) RJ samples stored at +4 °C. Bee-collected pollen had the greatest influence on the number of FAs in its mixture with honey.


Chronic pain in intensive care unit survivors: incidence, characteristics and side-effects up to one-year post-discharge.
Intensive care unit survivors experience significant physical and psychological problems, including chronic pain following discharge. The aim of this study was to observe the incidence, anatomical sites, intensity, and interference of chronic pain in intensive care unit survivors over a 1-year period. In addition, potential predictors of chronic pain were analysed. Data were collected during an intensive care unit follow-up programme as part of a quality improvement initiative. Data from the Brief Pain Inventory and from musculoskeletal assessment were examined, alongside demographic data from the patient. Data were collected from patients at baseline and at a 1-year follow-up appointment. Data from 47 intensive care unit survivors were included in this study. In 66% (n = 31) of the patients a "new" chronic pain that did not exist before their stay in the intensive care, was reported. Pain intensity in this patient group was "moderate"' and did not improve significantly over the 1-year period. Although pain interference with life decreased over the study period, it was still the most common cause of reduced enjoyment of life and reduced employment at 1-year follow-up. Chronic pain is associated with morbidity in intensive care unit survivors. Pain interference, but not pain intensity, improved significantly in the first year after discharge. Further multi-centre research is required to elucidate the chronic pain experience.


A framework for evaluating image segmentation algorithms.
The purpose of this paper is to describe a framework for evaluating image segmentation algorithms. Image segmentation consists of object recognition and delineation. For evaluating segmentation methods, three factors-precision (reliability), accuracy (validity), and efficiency (viability)-need to be considered for both recognition and delineation. To assess precision, we need to choose a figure of merit, repeat segmentation considering all sources of variation, and determine variations in figure of merit via statistical analysis. It is impossible usually to establish true segmentation. Hence, to assess accuracy, we need to choose a surrogate of true segmentation and proceed as for precision. In determining accuracy, it may be important to consider different 'landmark' areas of the structure to be segmented depending on the application. To assess efficiency, both the computational and the user time required for algorithm training and for algorithm execution should be measured and analyzed. Precision, accuracy, and efficiency factors have an influence on one another. It is difficult to improve one factor without affecting others. Segmentation methods must be compared based on all three factors, as illustrated in an example wherein two methods are compared in a particular application domain. The weight given to each factor depends on application.


Transcriptomic analysis of α-synuclein knockdown after T3 spinal cord injury in rats.
Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype β2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.


Eastern Cooperative Oncology Group Performance Score Is Associated With Survival After Radiotherapy of Bone Metastases from Prostate Cancer.
Understanding prognostic factors of survival are important for treatment personalization in cancer patients. This study aimed to identify such factors for patients irradiated for bone metastases from prostate cancer. Data from 74 patients irradiated between 01/2009 and 04/2019 were retrospectively evaluated. Ten characteristics were investigated for survival. Median survival in the entire cohort was 12 months. Survival rates at 3, 6, 9 and 12 months were 84%, 73%, 56% and 47%, respectively. On univariate analyses, the Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 was associated with improved survival (p<0.001), absence of visceral metastases (p=0.099) and only one irradiated metastatic site (p=0.099) showed a trend. On Cox regression analysis, only ECOG performance score (risk ratio=3.58, p<0.001) was significant. ECOG performance score is an independent prognostic factor of survival after irradiation of bone metastases from prostate cancer and may allow better personalization of care.


Fibroblast growth factor homologous factors modulate cardiac calcium channels.
Fibroblast growth factor (FGF) homologous factors (FHFs; FGF11-14) are intracellular modulators of voltage-gated Na+ channels, but their cellular distribution in cardiomyocytes indicated that they performed other functions. We aimed to uncover novel roles for FHFs in cardiomyocytes, starting with a proteomic approach to identify novel interacting proteins. Affinity purification of FGF13 from rodent ventricular lysates followed by mass spectroscopy revealed an interaction with junctophilin-2, a protein that organizes the close apposition of the L-type Ca2+ channel CaV1.2 and the ryanodine receptor 2 in the dyad. Immunocytochemical analysis revealed that overall T-tubule structure and localization of ryanodine receptor 2 were unaffected by FGF13 knockdown in adult ventricular cardiomyocytes but localization of CaV1.2 was affected. FGF13 knockdown decreased CaV1.2 current density and reduced the amount of CaV1.2 at the surface as a result of aberrant localization of the channels. CaV1.2 current density and channel localization were rescued by expression of an shRNA-insensitive FGF13, indicating a specific role for FGF13. Consistent with these newly discovered effects on CaV1.2, we demonstrated that FGF13 also regulated Ca(2+)-induced Ca2+ release, indicated by a smaller Ca2+ transient after FGF13 knockdown. Furthermore, FGF13 knockdown caused a profound decrease in the cardiac action potential half-width. This study demonstrates that FHFs not only are potent modulators of voltage-gated Na+ channels but also affect Ca2+ channels and their function. We predict that FHF loss-of-function mutations would adversely affect currents through both Na+ and Ca2+ channels, suggesting that FHFs may be arrhythmogenic loci, leading to arrhythmias through a novel, dual-ion channel mechanism.


The handicap principle and the argument of subversion from within.
This paper examines the very disparate positions that various actors have taken towards the argument of subversion from within (a classical argument against the evolution of altruism by group selection) in a set of related debates on group selection, altruism and the handicap principle. Using this set of debates as a case study, this paper argues that different applications of epistemic values were one of the factors behind the disagreements between John Maynard Smith and Amotz Zahavi over a number of important evolutionary issues. The paper also argues that these different applications were connected to important epistemological differences related in part (but not solely) to their disciplinary background. Apart from conflicting evolutionary views concerning the theoretical feasibility of the handicap effect, these antagonists both differed in the confidence they ascribed to mathematical modeling and over the hereditary basis for altruistic behavior.


Novel role of oxidants in the molecular mechanism of action of peroxisome proliferators.
Peroxisome proliferators are nongenotoxic rodent carcinogens that act as tumor promoters by increasing cell proliferation; however, their precise mechanism of action is not well understood. Oxidative DNA damage caused by leakage of hydrogen peroxide (H2O2) from peroxisomes was hypothesized initially as the mechanism by which these compounds cause liver tumors. It seems unlikely that oxidants of peroxisomal origin explain the mechanism of action of peroxisome proliferators because treatment with these compounds in vivo does not lead to increased H2O2 production. On the other hand, Kupffer cell-derived oxidants, such as superoxide, may play a role in initiating tumor nerosis factor-alpha (TNF-alpha) production that leads to hepatocyte proliferation. Peroxisome proliferators have been shown to activate Kupffer cells both in vitro and in vivo, and the use of Kupffer cell inhibitors such as methyl palmitate and dietary glycine have demonstrated that Kupffer cells are responsible for hepatocyte proliferation by mechanisms involve TNF-alpha. Moreover, peroxisome proliferators activate the transcription factor NF-kappaB, one of the major regulators of TNF-alpha expression, in Kupffer cells. Importantly, activation of NF-kappaB by peroxisome proliferators was shown to be oxidant-dependent, leading to the hypothesis that oxidants of Kupffer cell origin are involved in the mechanism of action. Many of the effects of peroxisome proliferators, including peroxisome induction and hepatomegaly, involve the peroxisome proliferator-activated receptor-alpha (PPARalpha). Recently, it was shown that peroxisome proliferator-induced cell proliferation and tumors require the PPARalpha. However, PPARalpha is not involved in TNF-alpha production by Kupffer cells because it is not expressed in this cell type. How it is involved in liver tumor remains unclear and one possible explanation is that both Kupffer cell TNF-alpha and parenchymal cell PPARalpha are required. Collectively, recent data are consistent with the hypothesis that oxidants play a role in signaling hepatocellular proliferation due to peroxisome proliferators via activation of NF-kappaB and incrase in mitogenic cytokines such as TNF-alpha.


Expression of key SARS-CoV-2 entry molecules in surgically obtained human retinal biopsies.
To investigate the presence of ACE2, TMPRSS2 and Furin, i.e., a key player in the ocular infection with SARS-COV-2, in surgically obtained human retinal tissue samples from SARS-CoV-2-negative patients, using gene expression analysis. The mechanisms and entry paths of ocular infections have been ill-defined so far. To better understand the possible entry routes, we used surgically explanted retinal tissue from nine patients that were not infected with SARS-CoV-2 and analyzed the message expression of the three key molecules that confer viral entry into cells using polymerase chain reaction. The median age of the patients (n = 9) included in the study was 52 years (IQR 48, 55). Eight patients underwent surgery for rhegmatogenous retinal detachment and one patient for tractional retinal detachment. Gene expression for the proteins studied was detected in all nine patients. The results of analysis by Livak's method (2001) demonstrated a median TMPRSS2 gene expression value of 20.9 (IQR 11.7, 33.7), a median ACE2 gene expression value of 2.09 (IQR 1.14, 2.79) and a median Furin gene expression value of 8.33 (IQR 5.90, 11.8). In conclusion, TMPRSS2, Furin and ACE2 are expressed in the retina and may contribute to the retinal involvement in COVID-19 patients. Expression may vary among individuals, which may explain why some patients may be more prone to retinal involvement during SARS-CoV-2 infection COVID-19 patients than others. Variability in the expression of TMPRSS2, Furin and ACE2 proteins themselves may also explain the presence or development of retinal symptoms of varying severity.


Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants.
Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users. Here, we hypothesized that a soft ABI could enhance biomechanical compatibility with the curved CN surface. We developed implantable ABIs that are compatible with surgical handling, conform to the curvature of the CN after placement, and deliver efficient electrical stimulation. The soft ABI array design relies on precise microstructuring of plastic-metal-plastic multilayers to enable mechanical compliance, patterning, and electrical function. We fabricated soft ABIs to the scale of mouse and human CN and validated them in vitro. Experiments in mice demonstrated that these implants reliably evoked auditory neural activity over 1 month in vivo. Evaluation in human cadaveric models confirmed compatibility after insertion using an endoscopic-assisted craniotomy surgery, ease of array positioning, and robustness and reliability of the soft electrodes. This neurotechnology offers an opportunity to treat deafness in patients who are not candidates for the cochlear implant, and the design and manufacturing principles are broadly applicable to implantable soft bioelectronics throughout the central and peripheral nervous system.


Selection of spermatozoa with high motility and quality from bovine frozen-thawed semen using the centrifuge-free device.
This study aimed to assess the potential of the centrifuge-free commercial device (MIGLIS®) in selecting functional frozen-thawed bovine sperm by migration-sedimentation, its effect on embryo development, and compare the potential with that of centrifugation-based techniques, including washing and Percoll density gradient centrifugation (DGC). In experiment 1, different dilutions (1.5×, 2×, and 3×) of frozen-thawed spermatozoa were assessed to identify the adequate one for the MIGLIS method. In experiment 2, the recovery rates, quality, and reactive oxygen species (ROS) concentrations of the spermatozoa selected using MIGLIS, washing, and Percoll DGC were compared. In experiment 3, the resultant in vitro fertilised embryos from spermatozoa selected using the three methods were evaluated for blastocyst formation rates and intracellular ROS concentrations at the 2-4 cell stage. The intracellular ROS concentrations were investigated using 2', 7'-dichlorodihydrofluorescein diacetate staining. Using the MIGLIS device, significantly more spermatozoa were recovered at 2× dilution compared with the other dilution ratio, but the motility was not affected by the dilution ratio. On the selection of spermatozoa using the three methods, employing MIGLIS decreased the recovery rates. However, the MIGLIS method increased motility, viability, and acrosome integrity rates compared to those in spermatozoa from the other methods. The ROS concentration of spermatozoa in the MIGLIS method was significantly lower than that in the washing method. Nevertheless, blastocyst formation rates were similar among the three methods, but the ROS concentration of early-stage embryos produced using MIGLIS was significantly lower than those produced using Percoll DGC. In conclusion, the MIGLIS method has the potential to select functional, high-quality frozen-thawed bovine spermatozoa.


Varicocele Embolization: Interventional Radiologist's Perspective.
The goal of this article is to review the patient selection criteria, technical pearls, and outcomes of percutaneous varicocele embolization. This article will provide a brief overview of the history of the procedure, angiographic approach, and materials used in contemporary embolization. The success rates and complications of the varicocele embolization will also be discussed.


Cell-type-specific interacting proteins collaborate to regulate the timing of Cyclin B protein expression in male meiotic prophase.
During meiosis, germ cell and stage-specific components impose additional layers of regulation on the core cell cycle machinery to set up an extended G2 period termed meiotic prophase. In Drosophila males, meiotic prophase lasts 3.5 days, during which spermatocytes upregulate over 1800 genes and grow 25-fold. Previous work has shown that the cell cycle regulator Cyclin B (CycB) is subject to translational repression in immature spermatocytes, mediated by the RNA-binding protein Rbp4 and its partner Fest. Here, we show that the spermatocyte-specific protein Lut is required for translational repression of cycB in an 8-h window just before spermatocytes are fully mature. In males mutant for rbp4 or lut, spermatocytes enter and exit meiotic division 6-8 h earlier than in wild type. In addition, spermatocyte-specific isoforms of Syncrip (Syp) are required for expression of CycB protein in mature spermatocytes and normal entry into the meiotic divisions. Lut and Syp interact with Fest independent of RNA. Thus, a set of spermatocyte-specific regulators choreograph the timing of expression of CycB protein during male meiotic prophase.


In-patient vs. day-hospital withdrawal treatment for chronic migraine with medication overuse and disability assessment: results at one-year follow-up.
Chronic headaches have increasingly become a focus within the field of head pain. Most patients with frequent headache eventually overuse their medications. The diagnosis of medication-overuse headache is clinically important, because patients rarely respond to preventive medications whilst overusing acute medications. Properly treating medication overuse and preventing relapse require specific therapeutic strategies and the recognition of the different factors that contribute to its development and perpetuation, including some behaviours and psychological elements that are important in sustaining the overuse of medication. Abrupt withdrawal is considered the first step for helping these patients to stop medication overuse. The possibility of withdrawal within a day-hospital setting is considered a therapeutic alternative for these patients and compared to in-patient withdrawal. Long-term results are discussed.


Oxidative stress and the etiology of insulin resistance and type 2 diabetes.
The condition of oxidative stress arises when oxidant production exceeds antioxidant activity in cells and plasma. The overabundance of oxidants is mechanistically connected to the multifactorial etiology of insulin resistance, primarily in skeletal muscle tissue, and the subsequent development of type 2 diabetes. Two important mechanisms for this oxidant excess are (1) the mitochondrial overproduction of hydrogen peroxide and superoxide ion under conditions of energy surplus and (2) the enhanced activation of cellular NADPH oxidase via angiotensin II receptors. Several recent studies are reviewed that support the concept that direct exposure of mammalian skeletal muscle to an oxidant stress (including hydrogen peroxide) results in stimulation of the serine kinase p38 mitogen-activated protein kinase (p38 MAPK), and that the engagement of this stress-activated p38 MAPK signaling is mechanistically associated with diminished insulin-dependent stimulation of insulin signaling elements and glucose transport activity. The beneficial interactions between the antioxidant α-lipoic acid and the advanced glycation end-product inhibitor pyridoxamine that ameliorate oxidant stress-associated defects in whole-body and skeletal-muscle insulin action in the obese Zucker rat, a model of prediabetes, are also addressed. Overall, this review highlights the importance of oxidative stress in the development of insulin resistance in mammalian skeletal muscle tissue, at least in part via a p38-MAPK-dependent mechanism, and indicates that interventions that reduce this oxidative stress and oxidative damage can improve insulin action in insulin-resistant animal models. Strategies to prevent and ameliorate oxidative stress remain important in the overall treatment of insulin resistance and type 2 diabetes.


Scientific facts behind creatine monohydrate as sport nutrition supplement.
Currently, strong efforts are being made toward demonstrating possible risks of using pure creatine monohydrate (Cr.H2O). In this article, scientific facts and considerations are presented, which support such concern. A further attempt is made to pursue the concept of possible risks of uncontrolled supplementation in athletes with pure Cr.H2O. The problem is viewed from the scientific evidence that a highly conservative mechanism of homeostatic feed-back inhibitory self-regulation of Cr biosynthesis in the body has been evolutionary developed. It is shown that numerous features characteristic to Cr biosynthesis, metabolism, and regulation allow to interpret its stimulatory action in the body as endocrine hormone-like. Based on this assumption, a practical approach for detecting altered links in Cr metabolism and biosynthesis under conditions of pure Cr.H2O overdosing, is suggested. Strategic considerations regarding early diagnosis, prognosis, and correction of the down-regulated endogenous Cr biosynthesis in athletes on continuous pure Cr.H2O supplementation, are discussed. As a high efficient and safe alternative to pure Cr.H2O, a complex nutrition supplement formula for elite athletes is proposed, which exploits natural alpha-ketoglutarate as a vehicle for delivering exogenous low molecular biologically-active compounds, including Cr.


A two-layer model of natural stimuli estimated with score matching.
We consider a hierarchical two-layer model of natural signals in which both layers are learned from the data. Estimation is accomplished by score matching, a recently proposed estimation principle for energy-based models. If the first-layer outputs are squared and the second-layer weights are constrained to be nonnegative, the model learns responses similar to complex cells in primary visual cortex from natural images. The second layer pools a small number of features with similar orientation and frequency, but differing in spatial phase. For speech data, we obtain analogous results. The model unifies previous extensions to independent component analysis such as subspace and topographic models and provides new evidence that localized, oriented, phase-invariant features reflect the statistical properties of natural image patches.


High glucose alters connexin 43 expression and gap junction intercellular communication activity in retinal pericytes.
To investigate the role of the gap junction protein, connexin-43 (Cx43) in the maintenance of retinal vascular homeostasis in diabetic retinopathy. In human retinal pericytes (HRPs) and bovine retinal pericytes (BRPs) grown for 7 days in normal (5 mM) or high (30 mM)-glucose medium, the Cx43 protein level was determined by Western blot analysis. Parallel experiments were performed in HRPs to determine the Cx43 mRNA level by RT-PCR, the distribution and localization of Cx43 protein by immunostaining, and gap junction intercellular communication (GJIC) activity by a scrape-loading dye transfer technique. Distribution and localization of Cx43 protein was also determined in pericyte-endothelial cell cocultures. Western blot analysis of the Cx43 protein level in HRPs and BRPs indicated reduced Cx43 expression in the high-glucose condition (69.1% +/- 17% of control, P = 0.004; 62.3% +/- 19% of control, P = 0.001, respectively). The Cx43 mRNA level in HRPs grown in high-glucose medium also showed significant reduction (71.4% +/- 16.8% of control, P = 0.02). The relative number of Cx43 plaques indicative of Cx43 localization at specific sites of contact between adjacent cells showed significant reduction in the high-glucose condition (61% +/- 10% of control, P = 0.002); similarly, a significant reduction in the number of plaques was observed in cocultures grown in high-glucose medium compared with those in normal medium (59.4% +/- 29% of control, P = 0.001). Cells with reduced Cx43 expression showed significantly reduced transfer of lucifer yellow (61% +/- 13% of control, P = 0.001; r = 0.9). High-glucose-induced downregulation of Cx43 expression and inhibition of GJIC in retinal pericytes may play a role in the disruption of vascular homeostasis in diabetic retinopathy.


The non-collagenous dentin matrix proteins are involved in dentinogenesis imperfecta type II (DGI-II).
Dentinogenesis Imperfecta type II (DGI-II) is a localized form of mesodermal dysplasia of the dentin affecting both the primary and permanent dentitions. This is an autosomal-dominant disease in which there is a disorder in dentin mineralization. Several studies have localized DGI-II to human chromosome 4 in the region 4q 12-21. Many ECM genes-such as OPN, DMP1, DMP2, DMP3 (DSPP), and BSP-have been mapped to the same locus. Biochemical studies indicated that dentin phosphophoryn (DMP2) might be a candidate gene in DGI-II. In this study, we have used histological and RFLP analyses of tissues from a DGI-II-affected patient, as compared with two normal controls, to determine if DMP1, 2, or 3 was linked to DGI-II. The histology of the affected tooth was very different in the DGI-II patient as compared with the normals. In particular, the dentinal tubules in the DGI-II patient were very irregular, which could be the result of perturbations in the process of dentin formation. Patient and control DNA samples were digested with EcoRI or PstI and Southern-hybridized with the DMP1, DMP2, and DMP3 cDNAs. Few differences in the restriction pattern were observed between affected and normal samples for DMP1 and DMP3-3' region (phosphophoryn-like sequences) probes. On the other hand, DMP2 showed a dramatic shift in the restriction pattern in DGI-II. This study suggests that the different restriction enzyme digestion profiles of the DNA from the DGI-II patient, as probed by DMP2, might be related to the defective mineralization of dentin in DGI-II.


Role of mitochondrial translocator protein (18 kDa) on mitochondrial- related cell death processes.
The 18 kDa translocator protein (TSPO) is able to modulate several mitochondria-related cell death processes due to close association with proteins and other molecules involved to the mitochondrial permeability transition pore. In this way, herein we review cell death mechanisms targeting mitochondria, including programmed cell death type I, II and III. Several proteins involved in these cell death processes and with a possible interplay with the TSPO are also discussed including the voltage dependent anion channel, the adenine nucleotide transporter, cardiolipin, and the Bcl-2 family proteins. Noteworthy, TSPO has been also implicated in various other functions including mitochondrial respiration, immune and phagocytic host-defense response, microglial activation, inflammation, cell growth and differentiation, cancer, cell proliferation, ischemia, and mental and neuropathological disorders. We focused in recent studies of the TSPO particularly on cancer and neurodegeneration, thus presenting the TSPO as a core element in the role of mitochondria in diseases and related processes. Clinical benefit may be attainable by increasing pharmacological knowledge related to the TSPO. Recent patents typically relate to diagnosis and treatment of TSPO-related pathological conditions including cancer, and inflammatory conditions, as well as disorders associated with central nervous system, such as neurodegeneration, convulsions, anxiety, mental disorders, and dementia.


Intracellular potassium activity in the rabbit proximal straight tubule.
Double-barreled liquid ion-exchanger microelectrodes were used to measure basolateral membrane potential (VBL) and intracellular potassium activity (aiK) in superficial proximal straight tubules (sPST) of the rabbit perfused in vitro. The mean +/- SE (number of cells in parentheses) value of VBL was -37.8 +/- 2.49 (20) vM and aiK was 48.6 +/- 2.27 (20) mM. The calculated Nernst equilibrium potential (EK) across the basolateral membrane was -68 mV. Lowering both potassium concentration to 0.1 mM reversibly decreased both VBL and aiK to -12.2 +/- 1.21 (19) mV and 11.3 +/- 1.29 (19) mM, respectively. Bath ouabain (10(-5) resulted in similar changes. These results demonstrate that intracellular potassium is actively accumulated in sPST perfused in vitro and that accumulation results primarily from Na-K-ATPase activity in the basolateral membrane. During recovery from low K bath, the temporal relationship between VBL and aiK and the effects of ouabain and high K bath on recovery are used to demonstrate directly electrogenic pumping. Lowering bath pH to 6.7 (HCO-3 = 5 mM) and the presence of 0.5 mM BaCl2 in the bath resulted in a large and rapid depolarization of VBL with little or no change in aiK. These results suggest that the response of VBL to both maneuvers is caused by a decrease in potassium permeability of the basolateral membrane.


Distribution of delta 9-tetrahydrocannabinol in the mouse.
1. The distribution of Delta(9)-tetrahydrocannabinol-(14)C in the pregnant and nonpregnant mouse is very similar. High concentrations of radiolabel can be seen in the maternal liver, spleen, lungs, brown fat, adrenal glands, mammary glands, yolk sac placenta and corpora lutea. In the pregnant mouse Delta(9)-THC crosses the placenta and enters the foetuses in very low concentrations, with no apparent selective intrafoetal radiolabel accumulation sites. Autoradiograms showing the distribution of (14)C-cannabinoid 2 h after dosing are presented.2. A small amount of maternal liver and foetal tissue was removed from the mice, used for autoradiography and extracted with ethyl acetate. Most of the radiolabel in these tissues was solvent extractable and was separated by thin layer chromatography into two fractions, THC and metabolites.3. It appears that most of the cannabinoid is present in a free rather than conjugated form.


[CDKN2A-mutation in a family with hereditary malignant melanoma].
Malignant melanoma (MM) is a frequent form of cancer with increasing incidence. 6-10% of patients with MM report a family history of MM, and in most populations 2% of unselected cases of MM carry a CDKN2A mutation. tvWe present a family with 24 cases of MM in nine persons from several generations, caused by a previously undescribed germ-line intronic mutation in CDKN2A. Through genetic counselling and genetic testing high-risk persons in the family are located and offered regular screening for MM.


Gallbladder motility and cholesterol crystallization in bile from patients with pigment and cholesterol gallstones.
Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics. Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients. Fasting gallbladder volume was significantly (P < 0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P < 0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019). Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.


Metal-Organic Frameworks as Potential Agents for Extraction and Delivery of Pesticides and Agrochemicals.
Pesticide contamination is a global issue, affecting nearly 44% of the global farming population, and disproportionately affecting farmers and agricultural workers in developing countries. Despite this, global pesticide usage is on the rise, with the growing demand of global food production with increasing population. Different types of porous materials, such as carbon and zeolites, have been explored for the remediation of pesticides from the environment. However, there are some limitations with these materials, especially due to lack of functional groups and relatively modest surface areas. In this regard, metal-organic frameworks (MOFs) provide us with a better alternative to conventionally used porous materials due to their versatile and highly porous structure. Recently, a number of MOFs have been studied for the extraction of pesticides from the environment as well as for targeted and controlled release of agrochemicals. Different types of pesticides and conditions have been investigated, and MOFs have proved their potential in agricultural applications. In this review, the latest studies on delivery and extraction of pesticides using MOFs are systematically reviewed, along with some recent studies on greener ways of pest control through the slow release of chemical compounds from MOF composites. Finally, we present our insights into the key issues concerning the development and translational applications of using MOFs for targeted delivery and pesticide control.


Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury.
Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane-anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal-dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non-adrenergic, non-cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal-dependent mechanisms which increase the resistance of the gastric mucosa to injury.