Cell-specific metallothionein gene expression in mouse decidua and placentae.
Oligodeoxyribonucleotide excess solution hybridization, Northern blot and in situ hybridization were used to analyze metallothionein gene expression in mouse decidua and placentae during gestation. Metallothionein (MT) -I and -II mRNA levels were constitutively elevated, 11- and 13-fold, respectively, relative to the adult liver, in the deciduum (D8), and decreased coordinately about 6-fold during the period of development when the deciduum is replaced by the developing placenta (D10-16). Coincident with this decline, levels of MT mRNA increased dramatically in the visceral yolk sac endoderm. In situ hybridization established that MT-I mRNA was present at low levels in the uterine luminal epithelium (D4), but was elevated at the site of embryo implantation exclusively in the primary decidual zone by D5, and then in the secondary decidual zone (D6-8). Although low levels of MT mRNA were detected in total placental RNA, in situ hybridization revealed constitutively high levels in the outer placental spongiotrophoblasts. Analysis of pulse-labeled proteins from decidua and placentae established that these tissues are active in the synthesis of MT. The constitutively high levels of MT mRNA in decidua were only slightly elevated following injection of cadmium (Cd) and/or zinc (Zn), whereas in placentae they increased several-fold. MT mRNA levels were equally high in decidua and experimentally induced deciduomata (D8) which establishes that decidual MT gene expression is not dependent on the presence of the embryo or some embryo-derived factor. Although the functional role of MT during development is speculative, these results establish the concept that, from the time of implantation to late in gestation, the mouse embryo is surrounded by cells, interposed between the maternal and embryonic environments, which actively express the MT genes. This suggests that MT plays an important role in the establishment and maintenance of normal pregnancy.


Recent changes in atmospheric mercury deposition recorded in the sediments of remote equatorial lakes in the Rwenzori Mountains, Uganda.
We analyzed sediment cores collected from three equatorial zone lakes in the Rwenzori Mountains of Uganda for Hg and dated them using 210Pb. The results show that the lakes have been contaminated by anthropogenic Hg from atmospheric deposition and that the onset of Hg pollution in the region began at least by the late 19th century. Mercury accumulation in all sediment cores increased by about 3-fold since the mid-19th century, a similar increase to that shown in other remote regions worldwide. These results from tropical high-elevation sites are the first for this region and contribute to our understanding of global Hg pollution trends. The atmospheric boundary layer is at a higher altitude in equatorial areas than at midlatitudes, and therefore, Hg deposition in these regions may not be enhanced by diurnal penetration of tropospheric air and associated reactive gaseous mercury as has been reported for mountain lakes at higher latitudes. Furthermore, the relatively low abundance of atmospheric oxidants may limit the amount of gaseous elemental mercury oxidized to the reactive gaseous form in equatorial Africa. These Rwenzori Hg records therefore have important implications for the understanding of Hg dynamics at high elevations in equatorial regions.


Template-based prediction of protein function.
We discuss recent approaches for structure-based protein function annotation. We focus on template-based methods where the function of a query protein is deduced from that of a template for which both the structure and function are known. We describe the different ways of identifying a template. These are typically based on sequence analysis but new methods based on purely structural similarity are also being developed that allow function annotation based on structural relationships that cannot be recognized by sequence. The growing number of available structures of known function, improved homology modeling techniques and new developments in the use of structure allow template-based methods to be applied on a proteome-wide scale and in many different biological contexts. This progress significantly expands the range of applicability of structural information in function annotation to a level that previously was only achievable by sequence comparison.


Genotype distribution of hepatitis C virus in the province of Gaziantep, a 10-year evaluation.
Hepatitis C virus (HCV) can cause both acute and chronic hepatitis infections. Gaziantep is located southeast part of Turkey and has a border with Syria. More than 400,000 Syrian refugees live in Gaziantep. The aim of this study was to evaluate distribution of HCV genotypes among Syrian patients and in people who inject drugs.Serum samples form 1,628 individuals (786 female, 842 male) which were sent to our laboratory for genotyping between January 2013 and December 2022, were analyzed retrospectively. Three different HCV genotyping assays (Qiagen, RTA and Abbott) were used during the 10-year study period.Out of the 1,628 patients, genotype 1 was detected in 51.5%, genotype 3 in 21.4%, genotype 4 in 20%, genotype 5 in 4.6%, genotype 2 in 1.3%. Mixed genotype was found in 20 patients. Of the patients, 1,143 were Turkish patients and among those patients genotype 1 (66.8%) was the most common genotype followed by genotype 3 (29%). Among Syrian patients (n = 477), genotype 4 (64.2%) was predominant genotype followed by genotype 1 and genotype 5. Genotype 3 was detected in 277 (79.6%) prisoners. All of them were male and probably the main source of HCV infection was intravenous drug abuse. While genotypes 1 and 4 were common in females, genotypes 1 and 3 were common in males.In the future genotype 3 may become an increasing problem due to the persons who inject drugs. Less frequent genotypes such as 4 and 5 may become more frequent due to Syrian patients.


[The application of transcervical non-inflatable endoscopic posterior inferior sternocleidomastoid approach in thyroid surgery].
Objective:To investigate the clinical efficacy and safety of transcervical non-inflatable endoscopic thyroidectomy through the posterior inferior sternocleidomastoid approach. Methods:From December 2022 to May 2023, the clinical data of 35 patients with papillary thyroid carcinoma treated by transcervical non-inflatable endoscopic surgery via posterior inferior sternocleidomastoid approach were retrospectively analyzed. There were 14 males and 21 females, with an average age of 44.7 years. The operation time, bleeding volume, postoperative recovery, complications and follow-up were recorded. Results:All 35 patients successfully completed the surgery, with an average operation time of 4 hours and 7 minutes, an average bleeding volume of 14 ml, and an average postoperative hospital stay of 3.5 days. There were no serious complications and no obvious neck discomfort during postoperative follow-up. Conclusion:Transcervical non-inflatable endoscopic thyroidectomy via posterior inferior sternocleidomastoid approach is safe and effective, with fast postoperative recovery,high appearance satisfaction and good neck comfort.


Combination of rituximab and short-term glucocorticoids in the treatment of anti-phospholipase A2 receptor antibody positive idiopathic membranous nephropathy.
Rituximab (RTX) has been the first option in idiopathic membranous nephropathy (IMN). However, the clinical effect was not very satisfactory. This study aimed to explore the clinical efficacy and safety of the combination of RTX and glucocorticoids (GC) in anti-phospholipase A2 receptor (anti-PLA2R) antibody positive IMN. Sixty-six patients were randomly divided into RTX/GC group (RTX infusion plus short-term oral GC) and RTX group (RTX infusion alone) in this prospective cohort study. Complete remission (CR) and partial remission (PR) were the primary outcomes. Adverse events were the secondary outcomes. The laboratory index including serum albumin, 24 h urinary protein, serum creatinine, estimated glomerular filtration rate, and anti-PLA2R antibody titer were also monitored. All patients were followed for at least 12 months. During the 12-month follow-up, the composite remission rates in RTX/GC and RTX groups were 74.3% and 67.7%, and the CR rates were 34.3% and 19.4%, respectively. The median time of remission in RTX/GC group was shorter than the RTX group (P < 0.001). Compared with RTX monotherapy, the combination of RTX and GC significantly decreased the anti-PLA2R antibody titer (P = 0.028). No significant difference was observed in the incidence of adverse events. The results of the Kaplan-Meier survival analysis indicated that the cumulative CR rate and cumulative composite remission rate in RTX/GC group were all better than the RTX group (P = 0.043, P = 0.040, respectively). The combination of RTX and GC was better than RTX monotherapy without increasing the adverse events in the treatment of IMN.


Does the Brief-BESTest Meet Classical Test Theory and Rasch Analysis Requirements for Balance Assessment in People With Neurological Disorders?
The Brief Balance Evaluation Systems Test (Brief-BESTest) was recently proposed as a clinical tool for quickly measuring balance disorders, but its measurement properties warrant investigation. The study objective was to perform a detailed analysis of the psychometric properties of the Brief-BESTest by means of Classical Test Theory and Rasch analysis. This was an observational measurement study. Brief-BESTest data were collected from a sample of 244 participants. Internal consistency was analyzed with the Cronbach α and item-to-total correlations. Test-retest reliability and interrater reliability were investigated in a subgroup of 21 participants. The minimum detectable change at the 95% confidence level was calculated. Scale dimensionality was examined through Horn parallel analysis; this step was followed by exploratory factor analysis for ordinal data. Finally, data were examined using Rasch analysis (rating scale model). The Cronbach α was .89, and all item-to-total correlations were greater than .40. Test-retest reliability had an intraclass correlation coefficient (ICC) (2,1) of .94, and interrater reliability had an ICC (2,1) of .90. The minimum detectable change at the 95% confidence level was 4.30 points. The unidimensionality of the test was confirmed, but 1 item showed low communality. Rasch analysis revealed the inadequacy of response categories, 5 misfitting items, minor mistargeting, moderate person reliability (.80), and 2 pairs of locally dependent items. The sample was a cross-section of people who had balance disorders from different neurological etiologies and were recruited consecutively at a single rehabilitation facility. The Brief-BESTest was confirmed to have some acceptable-to-good reliability indexes when calculated according to Classical Test Theory, but the scale showed fairly limited sensitivity to change. Rasch analysis indicated that item selection should be improved from a psychometric point of view. Item redundancy needs to be reduced, and the metric coverage of the measured construct needs to be improved with new items.


Effects on the local immunity in the testis by exposure to di-(2-ethylhexyl) phthalate (DEHP) in mice.
Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been reported to induce spermatogenic disturbance through oxidant stress and affect the immune system as an adjuvant. However, the effect of DEHP on the testicular immune microenvironment has not yet been investigated. In the present study, we examined the testicular immune microenvironment after exposure to doses of DEHP, previously identified as no-observed-adverse-effect levels. Adult male mice were administered food containing 0%, 0.01% or 0.1% DEHP and then testes were analyzed. The results showed that a slight but significant spermatogenic disturbance appeared in the 0.1% DEHP group but not in the 0.01% DEHP group at 8 weeks. It was also demonstrated that lymphocytes and F4/80- and MHC class II- positive cells were significantly increased with the elevation of IL-10 and IFN-γ mRNA expressions in the testes of not only the 0.1% DEHP group but also the 0.01% DEHP group at 8 weeks. Histochemical analyses involving horseradish peroxidase (HRP) as a tracer showed that a little blood-borne HRP had infiltrated into the lumen of a few seminiferous tubules beyond the blood-testis-barrier in both the 0.1% and 0.01% DEHP groups at 8 weeks. This indicates that a dose of DEHP that has little effects on spermatogenesis can change the testicular immune microenvironment with functional damage of the blood-testis barrier.


The relation between the arthroscopic findings and functional outcomes in patients with septic arthritis of the knee joint, treated with arthroscopic debridement and irrigation.
The aim of this study was to evaluate the relation between arthroscopic findings and functional outcomes in patients with septic arthritis of the knee joint, treated with arthroscopic debridement and irrigation. Twenty patients (17 male, 3 female; mean age: 31 years [5-63 years]) with knee septic arthritis treated with arthroscopic debridement and irrigation in our clinic between 2004-2007 were included in the study. The decision for arthroscopic debridement was made based on the clinical findings, erythrocyte sedimentation rate, C-reactive protein level and the aspiration of the affected knee. During the arthroscopic debridement, the joint was staged according to Gachter criteria. Continuous irrigation system was set up for all cases following surgery. After the surgery, the Bussiere functional scale was used for clinical evaluation. The mean follow-up periodwas 29±11months (range 13-54 months). The McNemar test was used in comparing the results. The Spearman correlation coefficient was used in the correlation analysis. The level of significance was set at 0.05. The culture was positive in 3 cases, and negative in 8 cases who exhibited gram (+) cocci in gram stains. In nine cases, cultures were negative and no microorganisms were detected in gram stains. According to the arthroscopic Gachter classification, 4 cases (20%) were Stage 1, 10 cases (50%) were Stage 2, 5 cases (25%) Stage 3 and 1 case (5%) was Stage 4. There was a statistically significant difference between the mean functional score of the knees with differing Gachter stages (McNemar test, p=0.003). There was a statistically significant and strong correlation between Gachter score and functional results (correlation coefficient: 0.780; p<0.001). Advanced arthroscopic findings are associated with poor functional results in patients with septic arthritis of the knee joint. In addition, the time between the initial symptoms and the surgery directly affects the functional results.


Family planning in Taiwan, Republic of China: Progress and prospects.
Abstract The family planning programme in Taiwan is considered to have been most successful and has been systematically evaluated. In the light of some expressed scepticism, however, its impact on fertility will have to be carefully reviewed. The present article discusses six specific problems : How many women have accepted the Lippes loops or pills offered in the programme ? How long will the loop stay in utero ? What proportion of married women is currently wearing the loops ? What changes have occurred in the knowledge-attitude-practice (KAP) of family planning among the target population ? How many births have been prevented by the IUD programme ? And finally, How much has fertility declined ? The fertility decline in Taiwan has been accelerating since the programme started in 1964. Approximately 40% of the decline in the birth rate, from 36.3 in 1963 to 27.7 in 1969, or 8.5 points per 1,000 in six years, however, was due to changes in age structure and delayed marriage. An increasing proportion of girls of marriageable age and a possible increase in the fecundability of the population will work against the programme's objective. Concerted efforts and heavier investment are essential for the final success of the programme.


Laparoscopic treatment of tubal pregnancy.
Seventeen tubal pregnancies were treated successfully with a laparoscopic procedure over the past four years. Four different laparoscopic techniques were used: salpingectomy, partial salpingectomy (midtube resection), fimbrial expression, and salpingotomy. "Preventive hemostasis" using vasopressin has made salpingotomy our treatment method of choice. Ruptured tubal pregnancy was not considered a contraindication to laparoscopic treatment. Four of the six women who were trying to conceive and were followed for longer than six months have had documented intrauterine pregnancies; one woman subsequently developed a contralateral tubal pregnancy which was treated by laparoscopic salpingotomy. Tubal ectopic pregnancy, even in the presence of rupture, can be managed effectively by a variety of laparoscopic techniques with benefits including minimal incision, short hospitalization, early return to full activity, and in many cases, a patent tube.


[Alcohol-induced cognitive disorder: alcohol dementia].
Cognitive impairment is frequently observed in patients with alcohol misuse or alcohol addiction. Multiple cognitive functions are reduced in these patients. Frontal lobe functions, as planning, abstract thinking, set shifting or continuous performance are most frequently affected. Alcohol amnestic syndrome, alcohol dementia and the Wernicke-Korsakow-Syndrome constitute distinct entities. Alcohol dementia follows the diagnostic criteria of dementia with clear evidence for alcohol abuse or alcohol addiction. The diagnostic procedure of alcohol-induced cognitive impairment includes medical history, physical and neuropsychiatric examinations; laboratory examinations, neuropsychological assessment, brain imaging and electroencephalographic recordings. At the moment, there are no established treatment options for alcohol-induced cognitive impairment. Some evidence is provided that nootropics might be of benefit. Alcohol abstinence is a most important step. Psychosocial interventions are essential to support the patients in their daily activities.


Mass spectrometry protein expression profiles in colorectal cancer tissue associated with clinico-pathological features of disease.
Studies of several tumour types have shown that expression profiling of cellular protein extracted from surgical tissue specimens by direct mass spectrometry analysis can accurately discriminate tumour from normal tissue and in some cases can sub-classify disease. We have evaluated the potential value of this approach to classify various clinico-pathological features in colorectal cancer by employing matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). Protein extracts from 31 tumour and 33 normal mucosa specimens were purified, subjected to MALDI-Tof MS and then analysed using the 'GenePattern' suite of computational tools (Broad Institute, MIT, USA). Comparative Gene Marker Selection with either a t-test or a signal-to-noise ratio (SNR) test statistic was used to identify and rank differentially expressed marker peaks. The k-nearest neighbours algorithm was used to build classification models either using separate training and test datasets or else by using an iterative, 'leave-one-out' cross-validation method. 73 protein peaks in the mass range 1800-16000Da were differentially expressed in tumour verses adjacent normal mucosa tissue (P < or = 0.01, false discovery rate < or = 0.05). Unsupervised hierarchical cluster analysis classified most tumour and normal mucosa into distinct cluster groups. Supervised prediction correctly classified the tumour/normal mucosa status of specimens in an independent test spectra dataset with 100% sensitivity and specificity (95% confidence interval: 67.9-99.2%). Supervised prediction using 'leave-one-out' cross validation algorithms for tumour spectra correctly classified 10/13 poorly differentiated and 16/18 well/moderately differentiated tumours (P = < 0.001; receiver-operator characteristics - ROC - error, 0.171); disease recurrence was correctly predicted in 5/6 cases and disease-free survival (median follow-up time, 25 months) was correctly predicted in 22/23 cases (P = < 0.001; ROC error, 0.105). A similar analysis of normal mucosa spectra correctly predicted 11/14 patients with, and 15/19 patients without lymph node involvement (P = 0.001; ROC error, 0.212). Protein expression profiling of surgically resected CRC tissue extracts by MALDI-TOF MS has potential value in studies aimed at improved molecular classification of this disease. Further studies, with longer follow-up times and larger patient cohorts, that would permit independent validation of supervised classification models, would be required to confirm the predictive value of tumour spectra for disease recurrence/patient survival.


Well-being at work and its association with work-home interactions: a study of young Vietnamese employees.
Studying well-being at work and how it is related to employees' work-home interactions has been of great concern to both researchers and policy-makers in recent years. The aim of this study is to investigate the status of well-being at work of young Vietnamese employees working in Hanoi city and how dimensions of their work-home interaction contribute to their well-being at work. A self-administered questionnaire survey was conducted on 675 Vietnamese employees whose age was under 35 years. Demo and Paschoal's well-being at work scale and the Survey Work-Home Interaction - Nijmegen (SWING) scale were applied to measure employees' well-being at work and work-home interactions respectively. The control variables include employees' sex, marital status, working tenure, work position, mentoring, and type of organization. This study documented differences in the status of well-being at work between groups by gender, work position, mentoring, whereas no difference was found between groups in age, marital status, working tenure or types of organization. Regression results demonstrated that altogether positive work-home, negative work-home, positive home-work interactions and work position can explain quite well the variance of employees' well-being at work, and the predictive power of positive interaction for well-being at work was significantly stronger than that of work position and negative work-home interaction. Our results suggested that to promote employees' well-being at work, organizations should invest in boosting the positive interactions between work and home life of employees. Work position, gender issue and mentoring are also meaningful determinants of well-being at work.


Population-based normative data and language effects of the Immediate Post-Concussion Assessmentand Cognitive Testing (ImPACT).
When test results are interpreted based on the norms of the U.S. population, misdiagnoses of neurocognitive impairment could occur with subgroups of individuals whose demographic characteristics differ from the overall population. The present study compared locally-based normative test data of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) of high school athletes in Hawaii, where diverse ethnicity and bilingualism are prominent, versus published test norms. 8637 high school athletes in Hawaii underwent ImPACT baseline testing. Non-parametric group comparisons of age, sex, and language groups were performed. Classification ranges for the ImPACT Composite scores and Total Symptom of the Hawaii sample were presented in percentile ranks that corresponded to the published ImPACT normative tables. Mann-Whitney U Test indicated significant differences in ImPACT Verbal Memory, Visual Memory, Visual Motor Speed, and Reaction Time Composite scores between age groups and sexes, although the effect sizes were small. Kruskal-Wallis H Test indicated no differences among the language groups. Percentile ranks of the Hawaii scores were predominantly similar to the ImPACT norms, except for Visual Motor Speed in the Impaired and Borderline ranges. The findings suggest that locally based normative data should be considered for sub-populations that may differ from the general population. Language factors, such as bilingualism, did not have significant effect on the ImPACT scores.


[Change in the ATP content in the cells of Anabaena variabilis].
The content of ATP in the cells of Anabaena variabilis does not change during one day in the darkness as compared to that in the cells grown in the light, this suggesting the endogenous energy reserve of the cell. The level of ATP gradually decreases when the cells are incubated in the darkness during 25 days, but does not reach zero. The content of ATP increases for a short period in the light in the cells that have been incubated in the darkness during several days (up to 7 days). On the contrary, the level of ATP increases to a small extent and then falls in the cells grown in the light. These differences suggest disturbed coupling of the synthesis and utilization of ATP in the cells grown in the darkness. The content of ATP increases again in the darkness, confirming that the alga is capable of synthesizing ATP in the darkness.


[Isolated fourth ventricle: report of 2 cases].
Two cases of isolated fourth ventricle are reported, the first due to cerebellar haemorrhage, and the second due to congenital hydrocephalus with multiple shunt revisions and Dandy-Walker cyst. In our opinion, there are two basic treatment for isolated forth ventricle. The direct approach to the fourth ventricle is indicated when there is presence of an intraventricular cyst. The fourth ventricular shunting, independent of the supratentorial shunt, is the best treatments for patients with an isolated fourth ventricle without the presence of a cyst.


[Comparison of imaginal diets of various Syrphidae (Diptera) species].
The full amount and species composition of pollen from intestines of 11 species of Syrphidae (Arctophila fulva, Eristalis arbustorum, E. nemorum, E. pertinax, Helophilus pendulus, Myiatropa florea, Rhingia campestris, Sericomyia silentis, Syrphus baltheatus, S. ribessii and S. vitripennis), collected at the some place (Torma, Jogeva distr., Estonia) and at the some time (18-20 July 1989) have been studied. Maximum number of pollen grains is different fly species varied from 67,800 (Rh. campestris) up to 240,700 (S. silentis) grains, and average number from 25,560 (Rh. campestris) up to 115,880 (E. pertinax) grains. Maximum volume of pollen in different fly species varied from 1.5 (S. ribesii) up to 23.6 (S. baltheatus) mm3, and average volume from 0.36 up to 7.0 mm3 (the same species). The difference in a imaginal diets of Syrphidae are found, and the degree of difference does not correlate with a degree taxonomic affinity of species. The difference in strategy of a feeding behavior of two Syrphus species, that have similar diet, are marked: in intestines of 80% specimens of S. ribesii we found pollen grains of less that 7 plant species, whereas intestines of more than 88% specimens of S. vitripennis contained more than 8 species of grains. Distinction in alimentary preferences of different species of files can not be explained neither particularities of their morphology, nor their color preferences.


Experiences of emotional eating in an Acceptance and Commitment Therapy based weight management intervention (SWiM): A qualitative study.
Emotional eating is a barrier to weight management. Interventions based on Acceptance and Commitment Therapy (ACT) promote the acceptance of uncomfortable feelings, which can reduce the urge to use food as a coping mechanism. We aimed to explore how participants of an ACT-based weight management intervention (WMI) experience emotional eating and relevant intervention content. We conducted semi-structured telephone interviews with participants of a digital ACT-based guided self-help WMI. Fifteen participants were purposefully selected to represent a range of demographic characteristics and emotional eating scores. We used reflexive thematic analysis to explore experiences of emotional eating. We generated five themes. Participants improved emotional eating by disconnecting emotions from behaviours though increased self-awareness (theme 1) and by implementing alternative coping strategies, including preparation, substitution, and acceptance (theme 2). Most participants maintained improvements in emotional eating over time but wished for more opportunities to re-engage with intervention content, including more immediate support in triggering situations (theme 3). Participants who struggled to engage with emotional eating related intervention content often displayed an external locus of control over emotional eating triggers (theme 4). The perceived usefulness of the intervention depended on participants' prior experiences of emotional eating, and was thought insufficient for participants with complex emotional experiences (theme 5). This ACT-based WMI helped participants with emotional eating by improving self-awareness and teaching alternative coping strategies. Intervention developers may consider adding ongoing forms of intervention that provide both real-time and long-term support. Additionally, a better understanding of how to support people with an external locus of control and people with complex experiences of emotional eating is needed. Future research may explore ways of personalising WMIs based on participants' emotional needs.


Co-Deposition of Gold Nanoparticles and Metalloporphyrin Using the Langmuir-Blodgett (LB) Technique for Surface-Enhanced Raman Scattering (SERS).
The synergistic effect produced by metallic nanoparticles when incorporated into different systems empowers a research field that is growing rapidly. In addition, organometallic materials are at the center of intensive research with diverse applications such as light-emitting devices, transistors, solar cells, and sensors. The Langmuir-Blodgett (LB) technique has proven to be suitable to address challenges inherent to organic devices, since the film properties can be tuned at the molecular level. Here we report a strategy to incorporate gold nanoparticles (AuNPs) into the LB film by co-deposition in order to achieve surface-enhanced Raman scattering (SERS) of the zinc(II)-protoporphyrin (IX) dimethyl ester (ZnPPIX-DME). Prior to the LB co-deposition, the properties of the Langmuir monolayer of ZnPPIX-DME at the air-water interface, containing AuNPs in the subphase, are studied through the surface-pressure versus mean molecular area (π-A) isotherms. The ZnPPIX-DME+AuNPs π-A isotherm presented a significant shift to higher molecular area, suggesting an interaction between both ZnPPIX-DME molecules and AuNPs. Those interactions are a key factor allowing the co-deposition of both AuNPs and ZnPPIX-DME molecules onto a solid substrate, thus forming the LB film. SERS of ZnPPIX-DME was successfully attained, ensuring the spatial distribution of the AuNPs. Higher enhancement factors were found at AuNP aggregates, as a result of the intense local electromagnetic field found in the metal nanoparticle aggregates. The main vibrational bands observed in the SERS spectra suggest a physical adsorption of the ZnPPIX-DME onto the surface of AuNPs. The latter is not only in agreement with the interactions pointed out by the π-A isotherms but also suggests that this interaction is kept upon LB film co-deposition.


A host-vector system for analysis and manipulation of rifamycin polyketide biosynthesis in Amycolatopsis mediterranei.
Modular polyketide synthases (PKSs) are a large family of multifunctional enzymes responsible for the biosynthesis of numerous bacterial natural products such as erythromycin and rifamycin. Advanced genetic analysis of these remarkable systems is often seriously hampered by the large size (>40 kb) of PKS gene clusters, and, notwithstanding their considerable fundamental and biotechnological significance, by the lack of suitable methods for engineering non-selectable modifications in chromosomally encoded PKS genes. The development of a facile host-vector strategy for genetic engineering of the rifamycin PKS in the producing organism, Amycolatopsis mediterranei S699, is described here. The genes encoding all 10 modules of the rifamycin PKS were replaced with a hygromycin-resistance marker gene. In a similar construction, only the first six modules of the PKS were replaced. The deletion hosts retained the ability to synthesize the primer unit 3-amino-5-hydroxybenzoic acid (AHBA), as judged by co-synthesis experiments with a mutant strain lacking AHBA synthase activity. Suicide plasmids carrying a short fragment from the 5' flanking end of the engineered deletion, an apramycin-resistance marker gene, and suitably engineered PKS genes could be introduced via electroporation into the deletion hosts, resulting in the integration of PKS genes and biosynthesis of a reporter polyketide in quantities comparable to those produced by the wild-type organism. Since this strategy for engineering recombinant PKSs in A. mediterranei requires only a selectable single crossover and eliminates the need for tedious non-selectable double-crossover experiments, it makes rifamycin PKS an attractive target for extensive genetic manipulation.


Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease.
Diabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells. It contributes to the maintenance of glucose physiological levels namely by inhibiting insulin and glucagon secretion as well as controlling adiposity and satiation. IAPP is a highly amyloidogenic polypeptide forming intracellular aggregates and amyloid structures that are associated with β-cell death. Data also suggest the relevance of unprocessed IAPP forms as seeding for amyloid buildup. Besides the known consequences of hyperamylinemia in the pancreas, evidence has also pointed out that IAPP has a pathological role in cognitive function. More specifically, IAPP was shown to impair the blood-brain barrier; it was also seen to interact and co-deposit with amyloid beta peptide (Aß), and possibly with Tau, within the brain of Alzheimer's disease (AD) patients, thereby contributing to diabetes-associated dementia. In fact, it has been suggested that AD results from a metabolic dysfunction in the brain, leading to its proposed designation as type 3 diabetes. Here, we have first provided a brief perspective on the IAPP amyloidogenic process and its role in diabetes and AD. We have then discussed the potential interventions for modulating IAPP proteotoxicity that can be explored for therapeutics. Finally, we have proposed the concept of a "diabetes brain phenotype" hypothesis in AD, which may help design future IAPP-centered drug developmentstrategies against AD.


Soy protein diet, but not Lactobacillus rhamnosus GG, decreases mucin-1, trefoil factor-3, and tumor necrosis factor-α in colon of dextran sodium sulfate-treated C57BL/6 mice.
The incidence of inflammatory bowel diseases has increased during recent decades. Within the colon, the families of mucins (MUC) and trefoil factors (TFF) facilitate mucosal protection. Probiotic administration influences the intestinal MUC layer. Additionally, food components may affect gut microflora or have direct effects on the MUC barrier. Our objective was to determine whether diet and/or Lactobacillus rhamnosus GG (LGG) would mediate dextran sodium sulfate (DSS)-induced colitis by altering expression of the MUC and TFF genes. C57BL/6 mice were fed diets containing 20% (wt:wt) casein, soy, or whey proteins with or without LGG for 12 d. Seven days after starting LGG diets, the mice were given 2% DSS in drinking water for 4 d. Two additional casein groups with or without LGG were given tap water, for a total of 8 groups. One day after the DSS treatment, the mice were killed and the colon and cecum tissues and cecum contents were collected and analyzed by qRT-PCR. Whey protein significantly increased cecal LGG content compared with the other diets. In the casein diet groups, MUC1 and TFF-3 expression in colon was significantly induced by DSS independent of LGG. Compared with other DSS-treated groups, soy protein decreased MUC-1 and TFF-3 in the colon. Similarly, soy protein decreased the impact of DSS on inflammatory scores, TNFα gene expression, and colon shortening. There was no overall effect of LGG on these measurements. In conclusion, soy protein suppressed the DSS-induced inflammatory stimulation of MUC, TFF, and TNFα gene expression independently of LGG.


Stable isotope enrichment in stratospheric nitrous oxide
Nitrous oxide is a greenhouse gas that also plays a role in the cycling of stratospheric ozone. Air samples from the lower stratosphere exhibit 15N/14N and 18O/16O enrichment in nitrous oxide, which can be accounted for with a simple model describing an irreversible destruction process. The observed enrichments are quite large and incompatible with those determined for the main stratospheric nitrous oxide loss processes of photolysis and reaction with excited atomic oxygen. Thus, although no stratospheric source needs to be invoked, the data indicate that present understanding of stratospheric nitrous oxide chemistry is incomplete.


Sphingosine kinase/sphingosine 1-phosphate axis: a new player for insulin-like growth factor-1-induced myoblast differentiation.
Insulin-like growth factor-1 (IGF-1) is the most important physiological regulator of skeletal muscle progenitor cells, which are responsible for adult skeletal muscle regeneration. The ability of IGF-1 to affect multiple aspects of skeletal muscle cell biology such as proliferation, differentiation, survival and motility is well recognized, although the molecular mechanisms implicated in its complex biological action are not fully defined. Since sphingosine 1-phosphate (S1P) has recently emerged as a key player in skeletal muscle regeneration, we investigated the possible involvement of the sphingosine kinase (SK)/S1P receptor axis on the biological effects of IGF-1 in murine myoblasts. RNA interference, chemical inhibition and immunofluorescence approaches were used to assess the role of the SK/S1P axis on the myogenic and mitogenic effects of IGF-1 in C2C12 myoblasts. We show that IGF-1 increases SK activity in mouse myoblasts. The effect of the growth factor does not involve transcriptional regulation of SK1 or SK2, since the protein content of both isoforms is not affected; rather, IGF-1 enhances the fraction of the active form of SK. Moreover, transactivation of the S1P2 receptor induced by IGF-1 via SK activation appears to be involved in the myogenic effect of the growth factor. Indeed, the pro-differentiating effect of IGF-1 in myoblasts is impaired when SK activity is pharmacologically inhibited, or SK1 or SK2 are specifically silenced, or the S1P2 receptor is downregulated. Furthermore, in this study we show that IGF-1 transactivates S1P1/S1P3 receptors via SK activation and that this molecular event negatively regulates the mitogenic effect elicited by the growth factor, since the specific silencing of S1P1 or S1P3 receptors increases cell proliferation induced by IGF-1. We demonstrate a dual role of the SK/S1P axis in response to myoblast challenge with IGF-1, that likely is important to regulate the biological effect of this growth factor. These findings add new information to the understanding of the mechanism by which IGF-1 regulates skeletal muscle regeneration.


Drug prescribing in the elderly.
Napoleon I (1769-1821) said: "I do not wish two diseases, one nature made and one man made." In no other area of medical practice is this more apt than in that concerned with the care of the elderly. The dangers of inappropriate drug prescribing are heightened in the elderly for a number of reasons related to certain patterns of illness in this age group.


Pulse compression using a tapered microstructure optical fiber.
We calculate the pulse compression in a tapered microstructure optical fiber with four layers of holes. We show that the primary limitation on pulse compression is the loss due to mode leakage. As a fiber's diameter decreases due to the tapering, so does the air-hole diameter, and at a sufficiently small diameter the guided mode loss becomes unacceptably high. For the four-layer geometry we considered, a compression factor of 10 can be achieved by a pulse with an initial FWHM duration of 3 ps in a tapered fiber that is 28 m long. We find that there is little difference in the pulse compression between a linear taper profile and a Gaussian taper profile. More layers of air-holes allows the pitch to decrease considerably before losses become unacceptable, but only a moderate increase in the degree of pulse compression is obtained.


Retrovirus-related sequences in human DNA: detection and cloning of sequences which hybridize with the long terminal repeat of baboon endogenous virus.
Human DNA sequences which hybridized with the long terminal repeats (LTR) of baboon type C virus M7 were detected by non-stringent blot hybridization. About 7 to 10 discrete bands of the LTR-related sequences were commonly observed in the DNAs from four independent human cell lines after digestion with either Eco RI, Hind III or Bam HI. The amounts of these sequences were more abundant in tumor cell lines than in a non-malignant cell line. The human sequences related to the M7 LTR seemed to be located at relatively specific sites on the cell DNA. The human DNA clones which hybridized with M7 LTR were detected in the human DNA library described by Lawn et al. (Cell 15, 1157-1174, 1978), at a frequency of about 300 per haploid genome. Five clones were isolated which shared different extent of homology with M7 LTR and whose restriction maps were totally different one another. The DNA structures of two of them resembled the genome of retroviruses. These results suggest the presence of various types of the LTR-related sequences in human DNA: some of them might represent endogenous virus genomes of human cells.


Direct-to-consumer prescription drug advertising, 1989-1998. A content analysis of conditions, targets, inducements, and appeals.
We conducted a content analysis of consumer-targeted prescription drug advertisements to explore trends in prevalence, shifts in the medical conditions for which drugs are promoted, reliance on financial and nonmonetary inducements, and appeals used to attract public interest. We collected the drug advertisements appearing in 18 consumer magazines from 1989 through 1998. Two judges independently coded each advertisement and placed it in a category pertaining to the target audience, use of inducements, and product benefits (mean kappa=0.93). We employed descriptive statistics, cross-tabulations, and curve estimation procedures. A total of 320 distinct advertisements were identified, representing 101 brands and 14 medical conditions. New advertisement and brand introductions increased dramatically during this decade. Advertisements for drugs used for dermatologic, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and obstetric/gynecologic conditions were most common. Almost all of the advertisements were aimed at the potential user of the drug, not third-party intermediaries such as parents and spouses. Although most advertisements were gender-neutral, women were more likely to be exclusively targeted. One eighth of the advertisements offered a monetary incentive (eg, a rebate or money-back guarantee), and one third made an offer of additional information in printed or audio/video form. The most common appeals used were effectiveness, symptom control, innovativeness, and convenience. Consumer-directed prescription drug advertising has increased dramatically during the past decade. The pharmaceutical industry is turning to this type of advertising to generate interest in its products. Our data may be useful to physicians who want to stay abreast of the treatments that are being directly marketed to their patients.


High-level exposure to lithium, boron, cesium, and arsenic via drinking water in the Andes of northern Argentina.
Elevated concentrations of arsenic in drinking water are common worldwide, however, little is known about the presence of other potentially toxic elements. We analyzed 31 different elements in drinking water collected in San Antonio de los Cobres and five surrounding Andean villages in Argentina, and in urine of the inhabitants, using ICP-MS. Besides confirmation of elevated arsenic concentrations in the drinking water (up to 210 microg/L), we found remarkably high concentrations of lithium (highest 1000 microg/L), cesium (320 microg/L), rubidium (47 microg/L), and boron (5950 microg/L). Similarly elevated concentrations of arsenic, lithium, cesium, and boron were found in urine of the studied women (N=198): village median values ranged from 26 to 266 microg/L of arsenic, 340 to 4550 microg/L of lithium, 34 to 531 microg/L of cesium, and 2980 to 16,560 microg/L of boron. There is an apparent risk of toxic effects of long-term exposure to several of the elements, and studies on associations with adverse human health effects are warranted, particularly considering the combined, life-long exposure. Because of the observed wide range of concentrations, all water sources used for drinking water should be screened for a large number of elements; obviously, this applies to all drinking water sources globally.


[Early radical corrective surgery in congenital deformities of the lateral and posterolateral portion of the vertebrae].
The article deals with the techniques of operation for semivertebra extirpation together with one-stage correction of the deformity with a contractor and anterior and posterior fixation of the spine. The operation was performed on 28 children as a result of which the spinal deformity was corrected, on the average, by 75% of the initial deformity in patients with scoliosis and by 50-66% in those with kyphoscoliosis. In 9 patients the initial deformity was corrected by more than 90%. Stable correction of the deformity was achieved in 84% of patients. The poor results (3 cases) were due to the use of a short compressing rod and erroneous choice of the material for spondylodesis. The operation is rekommended in progressing spinal deformities in young children under 3 years of age.


The use of IQ assessment in astronaut screening and evaluation.
The screening and evaluation of astronaut candidates usually includes measures of cognitive and intellectual capacity. Questions of ceiling effects and discriminability when evaluating individuals assumed to be of above average intelligence should be considered. The current study examines ceiling effects and discriminability on IQ assessment between pilots vs. mission specialists and men vs. women in the selection of astronaut candidates. IQ scores on 104 male and female Shuttle astronaut candidates as measured by the Multidimensional Aptitude Battery (MAB) were analyzed via factor analyses and tests of differences between genders, selection status, and job types. Total group, gender, and job type specificity and sensitivity and overall percent correctly classified were assessed on selected vs. unselected classification. Exploratory and confirmatory factor analyses failed to replicate the proposed factor configuration prompting reconfigured domain scores. Analyses of differences between gender, selection, and job categories found different results when using reconfigured IQ scores compared to the original formulation. The 10 subscales performed better than overall domain scores in sensitivity, specificity, and as significant predictors of individuals selected. Both versions of Verbal, Performance, and Full Scale IQ scores performed similarly regarding sensitivity and specificity. The reconfigured scores were better predictors of selection. Evidence for sensitivity, specificity, and classification prediction was better for subscales than overall domain scores. Some consideration to using reconfigured domain scores should be given to increase instrument utility.


Genetic variation in the androgen receptor gene and endometrial cancer risk.
Genetic variation in the androgen receptor (AR) gene may be associated with endometrial cancer risk based on the role of AR in regulating androgen levels. However, endometrial cancer studies reported inconsistent associations for a CAG repeat polymorphism in exon 1. Only one of these studies measured haplotype-tagging single nucleotide polymorphisms (htSNP) in AR and found statistically nonsignificant, decreased associations with endometrial cancer risk. In a population-based case-control study of 497 cases and 1,024 controls, we examined the CAG repeat polymorphism and six htSNPs (rs962458, rs6152, rs1204038, rs2361634, rs1337080, and rs1337082), which cover an estimated 80% of the known common variation in AR among Caucasian populations. CAG repeat length was not significantly associated with endometrial cancer [odds ratio per unit increase in the average number of repeats, 1.02 (95% confidence interval, 0.97-1.08); P(trend) = 0.29]. Minor alleles in three correlated htSNPs (rs6152, rs1204038, and rs1337082; r(2) >0.6) were associated with increased risk for endometrial cancer. The strongest association was observed for rs6152, with the odds ratios (95% confidence interval) being 1.13 (0.89-1.44) for heterozygous and 2.40 (1.28-4.51) for homozygous minor genotypes (P(trend) = 0.02) compared with homozygous major allele genotype. However, these associations were not statistically significant after permutation adjustment for multiple comparisons (P(trend) > 0.09). Haplotype analyses did not reveal any additional associations with endometrial cancer. Results from our study, taken together with previously published studies, provide little evidence of a consistent association between common genetic variation in AR and endometrial cancer risk.


Coronary artery trauma in chest wall injury.
Blunt chest trauma is a rare but important cause of coronary artery occlusion. Coronary damage may occur with even relatively minor chest injuries. The diagnosis of cardiac injury can be difficult in the setting of chest wall trauma as the usual findings of chest pain, cardiac enzyme assay and ECG are unreliable diagnostic tools. A case is presented demonstrating the diagnosis difficulties. An ECG abnormality in the setting of even minor chest injury requires assessment with echocardiography and, if abnormal, angiography. Currently angiography is the definitive diagnostic test and allows for therapeutic intervention as appropriate but coronary artery ultrasound may find a place in management. Further management depends on the time of diagnosis and the presence of other injuries.


Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143.
Immunotherapies have demonstrated efficacy across a diverse set of tumors supporting further evaluation in glioblastoma. The objective of this study was to evaluate the safety/tolerability and describe immune-mediated effects of nivolumab ± ipilimumab in patients with recurrent glioblastoma. Exploratory efficacy outcomes are also reported. Patients were randomized to receive nivolumab 3 mg/kg every 2 weeks (Q2W; NIVO3) or nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses, then nivolumab 3 mg/kg Q2W (NIVO1+IPI3). An alternative regimen of nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W for 4 doses, then nivolumab 3 mg/kg Q2W (NIVO3+IPI1) was investigated in a nonrandomized arm. Forty patients were enrolled (NIVO3, n = 10; NIVO1+IPI3, n = 10; NIVO3+IPI1, n = 20). The most common treatment-related adverse events (AEs) were fatigue (NIVO3, 30%; NIVO1+IPI3, 80%; NIVO3+IPI1, 55%) and diarrhea (10%, 70%, 30%, respectively). AEs leading to discontinuation occurred in 10% (NIVO3), 30% (NIVO1+IPI3), and 20% (NIVO3+IPI1) of patients. Three patients achieved a partial response (NIVO3, n = 1; NIVO3+IPI1, n = 2) and 8 had stable disease for ≥12 weeks (NIVO3, n = 2; NIVO1+IPI3, n = 2; NIVO3+IPI1, n = 4 [Response Assessment in Neuro-Oncology criteria]). Most patients (68%) had tumor-cell programmed death ligand-1 expression ≥1%. Immune-mediated effects mimicking radiographic progression occurred in 2 patients. Nivolumab monotherapy was better tolerated than nivolumab + ipilimumab; the tolerability of the combination was influenced by ipilimumab dose. These safety and exploratory findings merit further investigation of immunotherapies in glioblastoma.


Cross-sectional study of approaches to diagnosis and management of dogs with immune-mediated haemolytic anaemia in primary care and referral veterinary practices in the United Kingdom.
To determine whether veterinarians in primary care practices (PCPs) and board-certified clinicians (BCCs) approach treatment of dogs with immune-mediated haemolytic anaemia (IMHA) similarly, and whether practitioners with more experience treat similarly to those with less experience. We hypothesised those in PCPs would show more variation in their approach to similar cases than BCCs. A cross-sectional study was conducted by distributing a questionnaire to BCCs and veterinarians in PCPs. The questionnaire included direct questions and a number of clinical scenarios intended to capture approaches to common treatment problems. Questionnaire responses were received from 241 veterinarians, including 216 in PCPs and 25 BCCs. Veterinarians in both settings used similar tests for diagnosis of IMHA, but BCCs performed more tests to exclude underlying causes of 'associative' disease. All veterinarians reported use of similar initial dosages of glucocorticoids (median 2 mg/kg per day in both groups, p = 0.92) but those used by more experienced practitioners were higher than those with less experience. Most veterinarians made allowances for the weight of dogs, using lower prednisolone dosages in a clinical scenario involving a 40 kg dog compared to a 9 kg dog (p = 0.025 for PCP, p = 0.002 for BCC). BCCs reported greater use of combinations of immunosuppressive drugs (p<0.0001) and of antithrombotic drugs (p<0.0001); use of antithrombotic drugs was also less common among more experienced practitioners compared to less experienced. Approaches to treatment of dogs with IMHA differ between BCCs and those in PCP. These differences may affect design and implementation of future research studies and clinical guidelines.


Extrapyramidal symptoms due to dopamine-blocking agents in patients with AIDS encephalopathy.
The authors attempted to determine whether patients with AIDS are more susceptible to neuroleptic side effects than other patients. Retrospective chart review was used to assess the frequency and severity of extrapyramidal symptoms in patients with AIDS and psychotic patients without AIDS who had taken dopamine-blocking agents. The charts of 804 men younger than 50 years were reviewed, and patients were excluded if they had not taken dopamine blockers, had taken them for more than 1 month, had received concomitant antiparkinsonian agents, had focal brain lesions or histories of Parkinson's disease or meningitis, had used cocaine, amphetamines, or opiates within 1 month of admission, or, among the comparison group, had HIV risk factors. For the remaining 31 AIDS and 32 comparison patients, age, duration of dopamine blocker treatment, dose in chlorpromazine equivalents, and nature and severity of parkinsonian complications were recorded. The mean drug dose and body weight were significantly lower in the AIDS group. The likelihood of developing extrapyramidal symptoms was 2.4 times as high among the AIDS patients as among the comparison group. Such symptoms were developed by 50% of the AIDS patients who received less than 4 mg/kg of chlorpromazine equivalents per day and 78% of those who received more than 4 mg/kg per day. These preliminary results suggest that AIDS patients are more susceptible to extrapyramidal symptoms than psychotic patients without AIDS and that neuroleptics should be used cautiously and in lower doses for patients with AIDS.


Vasopressin-elicited refractoriness of the response to vasopressin in toad urinary bladder.
Incubation of the urinary bladder of Bufo marinus with high concentrations of vasopressin produces refractoriness to subsequent stimulation of water permeability by low concentrations of vasopressin. Development of refractoriness is directly dependent on concentration of vasopressin and duration of incubation with the hormone. Refractoriness develops in the absence of transepithelial water flow, is evident following a 2-h recovery period of incubation in hormone-free Ringer solution, and is reversed after prolonged incubation in hormone-free Ringer solution. Development and reversal of refractoriness is not altered by actinomycin D or cycloheximide. The steps at which refractoriness develops have been identified partially. Under different conditions, refractoriness involves: 1) reduced vasopressin-sensitive adenylate cyclase activity, 2) reduced epithelial cell cAMP accumulation in response to vasopressin the absence of demonstrable change in vasopressin-sensitive adenylate cyclase activity, cAMP phosphodiesterase activity, or loss of cAMP into the Ringer solution, and 3) refractoriness of water permeability response to exogenous cAMP.


Amiloidosis, a mysterious disease, still underestimated.
Amyloidosis, 150 years after being identified, still remains a mysterious disease, full of mystery, question marks and challenges, almost always ignored from the start, with terrible symptoms and terrible prognosis. The mechanics of the formation. persistence and setting of the amyloid fibrils are still under discussion. This article wishes to point out some of the main characteristics of this disease and the involved proteins by referring to the history. The pathogenesis, the histology, the diagnosis and a few aspects of the prognosis of this disease in the hope that future research will bring to light the answers for the mystery of amyloidosis along with more efficient therapies.


[Morphology of the epileptic neuron].
Using electron microscopy, the authors studied neurons and their synapses in the cortical foci of the brain in patients (1) with brain tumours attended by epileptic seizures, (2) with tumours accompanied by no paroxysms, and (3) with epilepsy of unknown etiology. The material was obtained in the interparoxysmal period. Morphometric study of the ultrastructure showed that morphological changes characteristic of epileptization were determined only in axodendritic (AD) and axospinal synapses in the form of their massive activation whose degree was calculated by collating the area of the "active zones" with the area of the entire synaptic surface. In epilepsy this ratio was 10-12 times higher than in tumours unattended with seizures. Activation of AD synapses should be considered as an ultrastructural manifestation of epileptization of the neuron while its extension should be seen as a criterion of the morphological diagnosis of the disease itself.


Evaluating the combined effect of alcohol-involved and un-helmeted riding on motorcyclist fatalities in Taiwan.
Alcohol-involved riders tend to engage in other risk-taking behaviours such as un-helmeted riding which could further increases injury severity. The combined effect of alcohol-involved and un-helmeted riding on fatal injuries is rarely investigated. This study investigated the interaction effect between blood alcohol concentration and helmet use on fatal injuries. This study used the National Taiwan Traffic Crash Dataset for the period from 2011 to 2015. Data on road crashes involving a motorcycle and an automobile were extracted and analysed. Multiple logistic regression models were used to calculate the adjusted odds ratio (AOR). We calculated an interaction effect for blood alcohol concentration and helmet use based on STROBE guidelines. There were a total of 669,292 motorcyclist casualties; among these casualties, 3459 (0.5 %) motorcyclists sustained fatal injuries. Alcohol-involved riders were 9.47 times (AOR = 9.47; 95 % CI = 8.75-10.25) more likely than sober ones to sustain fatal injuries. Alcohol-involved and un-helmeted riders were approximately 18 times (AOR = 18.1; CI: 15.9-20.4) more likely to sustain fatal injuries than sober and helmeted riders. Riders involved in head-on crashes and approach-turn motorcycle crashes had an increased probability of sustaining fatal injuries by 240 % (AOR = 3.4; 95 % CI = 2.91-4.09) and 132 % (AOR = 2.3; 95 % CI = 2.016-2.67), respectively. This study found that alcohol-involved riding acts synergistically with un-helmeted riding to increase motorcyclist injury severity.


Prevention of lpr-graft-versus-host disease and transfer of autoimmune diseases in normal C57BL/6 mice by transplantation of bone marrow cells plus bones (stromal cells) from MRL/lpr mice.
C57BL/6 (B6) (H-2b) mice were lethally irradiated and then reconstituted with T cell-depleted MRL/Mp-lpr/lpr (MRL/lpr) (H-2k) bone marrow cells. The mice showed a short survival with splenic atrophy and fibrosis, as previously described as lpr-graft-vs-host disease (GVHD). However, when these mice received bone marrow transplantation (BMT) plus bone grafts (to recruit donor-derived stromal cells) from MRL/lpr mice, they survived for almost 1 yr without showing GVH symptoms, but showing autoimmune symptoms such as elevated serum IgG2a concentrations, autoantibody production and glomerulonephritis. When MRL/lpr bone marrow cells plus MRL/+ bones (instead of MRL/lpr bones) were transplanted into B6 mice, such improved survival was also obtained, although the MRL/+ bone grafts were less effective in prolonging survival than MRL/lpr bone grafts. H-2 typing of stromal cells in the bone marrow of the B6 mice revealed that the stromal cells had been replaced by donor(H-2k) derived stromal cells. Analyses of TCR repertoires showed that the percentage of CD4+V beta 8.1,2+ cells significantly decreased in the B6 mice that received bone marrow transplantation plus bone grafts from MRL/lpr mice. These findings suggest that stromal cells present in the bone marrow play a crucial role in the development of lpr-GVHD and autoimmune diseases.


Using Machine Learning for Personalized Patient Adherence Level Determination.
The paper deals with using a machine-learning algorithm for patient adherence level determination. For this purpose, we developed a neural network using the Python language, Keras library, and PyCharm platform. We analyzed different medical data collected from medical staff, patient interviews, and measurements preprocessed using a fuzzy Mamdani algorithm. After analysing 369 records we received 79.4% of accuracy.


Differential expression of plasma membrane calcium pump mRNA isoforms in rat osteoblast-like cells.
This study was conducted to identify the plasma membrane Ca2+ transport ATPase (PMCA) mRNA isoforms expressed in rat osteoblast-like cells as PMCAs are likely to participate in calcium deposition in bone. We designed oligonucleotide primers for each PMCA isoform based on rat cDNA sequences in order to develop reverse transcription polymerase chain reaction (RT-PCR) assays. Rat kidney total RNA was used to validate the assays as we have shown that each isoform is present in kidney. When used in RT-PCR assays each primer pair gave rise to a single major product of the appropriate size. Southern blot analysis of the PCR products with oligonucleotide probes specific for each isoform revealed that each probe hybridized only to the expected product. Reamplification of purified PCR products with probe and antisense primers gave rise to products of appropriate size, further confirming the identity of the products. Using these primers we have identified the presence of transcripts for PMCA1, 2 and 4 in RNA from UMR-106 osteoblasts and PMCA1 in RNA from ROS 17/2.8 osteoblasts. We conclude that the two major rat cell lines used as models to study osteoblast function differentially express PMCA mRNA isoforms.


Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension.
Arterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans. To assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension. This cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (β-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores. The main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group. The study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving β-blockers and CCBs (0.38% for both β-blockers and CCBs at 1 year; 0.91% for β-blockers and 0.93% for CCBs at 3 years; β-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group. In this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension.


Phylogeny and biogeography of the American live oaks (Quercus subsection Virentes): a genomic and population genetics approach.
The nature and timing of evolution of niche differentiation among closely related species remains an important question in ecology and evolution. The American live oak clade, Virentes, which spans the unglaciated temperate and tropical regions of North America and Mesoamerica, provides an instructive system in which to examine speciation and niche evolution. We generated a fossil-calibrated phylogeny of Virentes using RADseq data to estimate divergence times and used nuclear microsatellites, chloroplast sequences and an intron region of nitrate reductase (NIA-i3) to examine genetic diversity within species, rates of gene flow among species and ancestral population size of disjunct sister species. Transitions in functional and morphological traits associated with ecological and climatic niche axes were examined across the phylogeny. We found the Virentes to be monophyletic with three subclades, including a southwest clade, a southeastern US clade and a Central American/Cuban clade. Despite high leaf morphological variation within species and transpecific chloroplast haplotypes, RADseq and nuclear SSR data showed genetic coherence of species. We estimated a crown date for Virentes of 11 Ma and implicated the formation of the Sea of Cortés in a speciation event ~5 Ma. Tree height at maturity, associated with fire tolerance, differs among the sympatric species, while freezing tolerance appears to have diverged repeatedly across the tropical-temperate divide. Sympatric species thus show evidence of ecological niche differentiation but share climatic niches, while allopatric and parapatric species conserve ecological niches, but diverge in climatic niches. The mode of speciation and/or degree of co-occurrence may thus influence which niche axis plants diverge along.


The human lumbar dorsal rami.
The L 1-4 dorsal rami tend to form three branches, medial, lateral, and intermediate, which are distributed, respectively, to multifidus, iliocostalis, and longissimus. The intertransversarii mediales are innervated by a branch of the dorsal ramus near the origin of the medial branch. The L 4 dorsal ramus regularly forms three branches while the L 1-3 levels the lateral and intermediate branches may, alternatively, arise from a short common stem. The L 5 dorsal ramus is much longer than the others and forms only a medial and an intermediate branch. Each lumbar medial branch innervates two adjacent zygapophysial joints and ramifies in multifidus, supplying only those fascicles which arise from the spinous process with the same segmental number as the nerve. The comparative anatomy of the lumbar dorsal rami is discussed and the applied anatomy with respect to 'rhizolysis', 'facet denervation' and diagnostic paraspinal electromyography is described.


Key Learnings During the Development of a Generic Data Collection Tool to Support Assessment of Freedom of Infection in Cattle Herds.
Various European Member States have implemented control or eradication programmes for endemic infectious diseases in cattle. The design of these programmes varies between countries and therefore comparison of the outputs of different control programmes is complex. Although output-based methods to estimate the confidence of freedom resulting from these programmes are under development, as yet there is no practical modeling framework applicable to a variety of infectious diseases. Therefore, a data collection tool was developed to evaluate data availability and quality and to collect actual input data required for such a modeling framework. The aim of the current paper is to present the key learnings from the process of the development of this data collection tool. The data collection tool was developed by experts from two international projects: STOC free (Surveillance Tool for Outcome-based Comparison of FREEdom from infection, www.stocfree.eu) and SOUND control (Standardizing OUtput-based surveillance to control Non-regulated Diseases of cattle in the EU, www.sound-control.eu). Initially a data collection tool was developed for assessment of freedom of bovine viral diarrhea virus in six Western European countries. This tool was then further generalized to enable inclusion of data for other cattle diseases i.e., infectious bovine rhinotracheitis and Johne's disease. Subsequently, the tool was pilot-tested by a Western and Eastern European country, discussed with animal health experts from 32 different European countries and further developed for use throughout Europe. The developed online data collection tool includes a wide range of variables that could reasonably influence confidence of freedom, including those relating to cattle demographics, risk factors for introduction and characteristics of disease control programmes. Our results highlight the fact that data requirements for different cattle diseases can be generalized and easily included in a data collection tool. However, there are large differences in data availability and comparability across European countries, presenting challenges to the development of a standardized data collection tool and modeling framework. These key learnings are important for development of any generic data collection tool for animal disease control purposes. Further, the results can facilitate development of output-based modeling frameworks that aim to calculate confidence of freedom from disease.


Six years of experience with a new surgical algorithm in developmental dysplasia of the hip in children under 18 months of age.
One hundred thirty-seven developmentally dysplastic hips of 107 children with a mean age of 11 months were treated by the same surgical algorithm. Following iliopsoas and adductor longus tenotomies by the Ferguson posteromedial approach, the operation was ended in case of arthrographically documented concentric reduction (Tönnis grade 1 reduction) and an open reduction was performed in case of nonanatomic arthrographic reduction (Tönnis grade 2 or 3 reduction). Mean follow-up was 4.2 years. The need for open reduction increased in preoperatively dislocated hips that were proximally displaced according to the Tönnis classification. Somewhat better latest acetabular index values were seen in hips having lower preoperative dislocation grades that were surgically treated before the age of 12 months. Rates of avascular necrosis of the femoral head, redislocation, and secondary operation were 13%, 1%, and 2%, respectively. The authors concluded that although mid-term results of this new surgical algorithm in developmental dysplasia of the hip was satisfactory in infants younger than 18 months of age, long-term follow-up is needed for better understanding of its use.


Alpha 2-adrenergic receptors on the circular smooth muscle of canine small intestine.
We have studied the distribution and properties of alpha 2-adrenergic receptors in the circular muscle layer (containing deep muscular plexus) of canine small intestine. Using radioactivity labelled rauwolscine, we located the binding sites to the neuronal membranes supporting the prejunctional action of alpha 2-adrenergic agents in the gut. Moreover, although the functional data to suggest the existence of postjunctional alpha 2-adrenergic receptors coupled to contraction are not available so far, we measured a substantial number of rauwolscine binding sites on the smooth muscle plasma membranes. Scatchard and Hill analyses of the saturation data were indicative of the presence of a single high affinity site (Hill coefficient 0.996) with a KD value of 8.8 nM and the maximum number of binding sites (Bmax) of 313 fmol/mg of protein. Competition studies suggested the presence of multiple subtypes of alpha 2-adrenoceptors.


Protein-losing enteropathy in systemic lupus erythematosus: case report.
Protein-losing enteropathy is rarely seen in patients with systemic lupus erythematosus. This clinical condition should be suspected in the presence of persistent hypoalbuminemia despite normal liver function, adequate protein intake, and no significant proteinuria. We report the case of a 48-year-old female with weight loss, cavity effusions (ascites and pleural effusion), and lower extremity edema. The diagnosis of lupus was established based on the presence of lymphopenia, proteinuria, ANA, and positive autoantibodies (anti-Sm, anti-DNA, and anti-Ro). Because hypoalbuminemia persisted even with corticosteroid therapy at the dose of 1 mg/kg, protein-losing enteropathy was diagnosed by use of Tc-99m albumin scintigraphy. After adding azathioprine to the treatment, the symptoms subsided and serum albumin levels improved.


Stability in negotiation games and the emergence of cooperation.
Consider a two-player game in which each player contributes a costly resource to the common good of the pair. For such contests, the Nash equilibrium contribution, x*, is one for which neither player can increase its pay-off by unilaterally altering its contribution from x*. We study an elaboration of this game, which allows the players to exchange x-offers back and forth in a negotiation phase until they converge to a final pair of contributions, x1 and x2. A significant feature of such negotiation games, hitherto unrecognized, is the existence of a set of neutrally stable equilibrium points in negotiation phase space. To explore the long-term evolutionary outcome of such games, we simulate populations containing various mixtures of negotiation strategies and, contrary to previous results, we often find convergence to a contribution that is more cooperative than the Nash equilibrium. Mathematical analysis suggests why this might be happening, and provides a novel and robust explanation for cooperation, that negotiation can facilitate the evolution of cooperative behaviour.


Effects of Self-Esteem on the Associations Between Infertility-Related Stress and Psychological Distress Among Infertile Chinese Women: A Cross-Sectional Study.
Anxiety and depression are the most common psychological causes of distress in infertile women. Our study aimed to evaluate the prevalence of depression and anxiety and investigate the effects of self-esteem on the association of infertility-related stress with depression and anxiety among infertile women. This study was conducted between December 2017 and May 2018. Questionnaires containing Fertility Problem Inventory (FPI), Rosenberg self-esteem scale (RSES) and Hospital Anxiety and Depression Scale (HADS) were distributed among 536 female infertility patients in Shenyang, China. Hierarchical linear regression analyses were used to examine the mediating and moderating role of self-esteem. Baron and Kenny's technique, asymptotic, and resampling strategies were used to confirm the mediating role of self-esteem on the associations between infertility-related stress with depression and anxiety. The prevalence of depression and anxiety was 27.9% and 42.2% among Chinese female infertility patients, respectively. Infertility-related stress was positively associated with depression and anxiety, whereas self-esteem was negatively associated with depression and anxiety. Additionally, the effects of infertility-related stress on depression and anxiety gradually decreased along with an increase in self-esteem. Meanwhile, self-esteem partially mediated the associations between infertility-related stress with depression and anxiety. A high prevalence of psychological distress was found among infertile women. Self-esteem mediated and moderated the effects of infertility-related stress on depression and anxiety. Additionally, infertility-related stress and self-esteem were associated with psychological distress, which explained why infertile women had a higher prevalence of depression and anxiety. Therefore, interventions that focus on self-esteem may be effective and should be used as a resource to combat mental health problems.


Understanding the financial burden of incomplete abortion: An analysis of the out-of-pocket expenditure on postabortion care in eight public-sector health care facilities in Dakar, Senegal.
Timely access to treatment is essential for women when they experience abortion complications. Out-of-pocket (OOP) expenditure is a known barrier to health care access. In 2018, we assessed the financial burden of accessing postabortion care (PAC) borne by women in Dakar, Senegal, where studies estimate that half of poor women with complications obtain PAC. We interviewed 729 women following discharge from PAC. Women reported expenditures on transportation, admission, treatment, family planning, hospitalisation, complementary tests, prescriptions, other medicines and materials. We compare women's OOP on PAC by expenditure category, type of treatment and facility type, and use multiple generalised linear regression analysis to explain variation in overall OOP and forecast it under alternate scenarios. The average OOP was USD $93.84. At health centres it was $65.47 and at hospitals it was $120.47. The average cost of PAC using dilation and curettage was $112.37, manual vacuum aspiration was $99.84, and misoprostol $61.80. Overall OOP on PAC amounts, on average, to 15% of the average monthly salary for women living in Dakar. Strategies that emphasise timely access to misoprostol for treating complications in primary care settings will address the contribution of OOP costs to Senegal's appreciable unmet need for PAC among the poor.


DNA polymerase beta is required for efficient DNA strand break repair induced by methyl methanesulfonate but not by hydrogen peroxide.
The most frequent DNA lesions in mammalian genomes are removed by the base excision repair (BER) via multiple pathways that involve the replacement of one or more nucleotides at the lesion site. The biological consequences of a BER defect are at present largely unknown. We report here that mouse cells defective in the main BER DNA polymerase beta (Pol beta) display a decreased rate of DNA single-strand breaks (ssb) rejoining after methyl methanesulfonate damage when compared with wild-type cells. In contrast, Pol beta seems to be dispensable for hydrogen peroxide-induced DNA ssb repair, which is equally efficient in normal and defective cells. By using an in vitro repair assay on single abasic site-containing circular duplex molecules, we show that the long-patch BER is the predominant repair route in Pol beta-null cell extract. Our results strongly suggest that the Pol beta-mediated single nucleotide BER is the favorite pathway for repair of N-methylpurines while oxidation-induced ssb, likely arising from oxidized abasic sites, are the substrate for long-patch BER.


[Mechanism analysis of Anti-BmNPV resistant strain NC99R].
Bombyx mori is a lepidopteran insect with important economic value. Bombyx mori nucleopolyhedrovirus (BmNPV) causes huge economic loss to silkworm industry in China every year. The objective of this study is to determine the anti-BmNPV mechanism of Bombyx mori strain NC99R, and to provide a basis for understanding the molecular mechanism of the silkworm resistance strain. The normal control Dazao (DZ) strain and the NC99R resistant strain were fed with occlusion bodies (OB). The median lethal dose (LD50) analysis of the DZ and NC99R showed that the LD50 of DZ was 1.2×10⁵ OBs/larva, while NC99R was 1.8×10⁶ OBs/larva. The LD50 of the NC99R was about 15 times higher than the DZ. The mortality of DZ and NC99R were analyzed, which were fed with 1×10⁶ OBs/larva and injection with 1×10⁶ BVs/larva. The results showed that the death peak of DZ was concentrated in the 4th to 6th day. And the death peak of NC99R was concentrated in the 6th to 8th day, with a delay of 1-2 days compared with the control. The BmNPV DNA copy number showed that the BmNPV genome in DZ proliferated rapidly. The copy number of BmNPV DNA in NC99R were increased slowly after oral infection and body injection. HE staining showed that midgut tissue has no significant difference between DZ and NC99R in the early stage of oral infection. At 96 h p.i., the nucleus of DZ midgut became larger and shedding. The NC99R had enlarged nuclei, but the cells were still arranged neatly. Finally, the expression of virus genes in different periods were analyzed by RT-PCR. The results indicated that the immediate early gene ie-1 expression levels began to down-regulate after 24 h p.i.. The early, late, and extremely late genes were also down-regulated, and finally maintained at a lower expression level.


Acquired and natural immunity to gonococcal infection in chimpanzees.
Despite the fact that gonorrhea is our most common reportable infectious disease, little is known about natural and acquired resistance to Neisseria gonorrhoeae. With the chimpanzee model, which mimics human gonococcal infection in signs, symptoms, and host response, a natural resistance to gonococcal challenge was found. One aspect of this natural resistance became evident when the cervix and oral pharynx resisted more gonococci than the urethra. Natural resistance was also shown when environmental factors were found to influence resistance to gonococcal pharyngitis. In addition to natural resistance a postinfection-acquired immunity to the gonococcus was demonstrated. Following gonococcal pharyngitis, this anatomical location successfully resisted more gonococci than were initially resisted. Similarly, more gonococci were successfully resisted in rechallenging the urethra. These findings are related to the clinic situation and suggest possible new approaches to gonorrhea control.


Cellular immune response to Marburg virus infection in cynomolgus macaques.
Marburg virus (MARV) causes a severe and usually lethal hemorrhagic disease in humans and non-human primates. Here, 16 cynomolgus macaques were experimentally infected with the Ci67 strain of MARV. Blood and spleen samples were collected at various time points after infection to study the immunological response to MARV. Beginning at day 2 and continuing throughout the course of the infection there was a rise in antigen-presenting cells in both the blood and spleen expressing MARV glycoprotein. Natural killer (NK) cells declined in the blood after infection (from 15% on day 0 to 5% on day 6), but a small increase was seen in the spleen samples. Little or no change in CD4(+) or CD8(+) T cells was observed out to day 6 post-exposure in blood, while there was a continual decline in the percentage of CD8(+) T cells in spleen samples. Circulating B cells (defined as CD20(+)) increased during the course of the infection as did CD4(+) CD8(+) (double-positive) T cells. Intracellular cytokine staining indicated that by day 6 a large population of leukocytes in the spleen were producing IFN-alpha; analysis of surface markers indicated that these cells were plasmacytoid dendritic cells based on their expression of CD123(+), but these cells had decreased expression of class II MHC. IL-6 production was detected late in the infection in CD14(+) spleen cells. These results suggest a robust innate immune response to MARV; however, this response was delayed relative to the infection.


The TLC model of palliative care in the elderly: preliminary application in the assisted living setting.
Substantial shortfalls in the quality of palliative care of the elderly can be attributed to 5 fundamental flaws in the way end-of-life care is currently delivered. First, palliative care is viewed as a terminal event rather than a longitudinal process, resulting in a reactive approach and unnecessary preterminal distress in elderly patients suffering from chronic, slowly progressive illnesses. Second, palliative care is defined in terms of a false dichotomy between symptomatic and disease-focused treatment, which distracts attention from the proper focus of healing illness. Third, the decision about whether the focus of care should be palliative is not negotiated among patients, family members, and providers. Fourth, patient autonomy in making treatment choices is accorded undue prominence relative to more salient patient choices, such as coming to terms with their place in the trajectory of chronic illness. Fifth, palliative care is a parallel system rather than an integrated primary care process. A new theoretical framework--the TLC model--addresses these flaws in the provision of palliative care for elderly persons. In this model, optimal palliative care is envisioned as timely and team oriented, longitudinal, collaborative and comprehensive. The model is informed by the chronic illness care, shared decision making, and comprehensive geriatric assessment research literature, as well as previous palliative care research. Preliminary results of an intervention for elderly assisted living residents based on the TLC model support its promise as a framework for optimizing palliative care of elders.


Structural-Functional Relationships Between Eye Orbital Imaging Biomarkers and Clinical Visual Assessments.
Eye diseases and visual impairment affect millions of Americans and induce billions of dollars in annual economic burdens. Expounding upon existing knowledge of eye diseases could lead to improved treatment and disease prevention. This research investigated the relationship between structural metrics of the eye orbit and visual function measurements in a cohort of 470 patients from a retrospective study of ophthalmology records for patients (with thyroid eye disease, orbital inflammation, optic nerve edema, glaucoma, intrinsic optic nerve disease), clinical imaging, and visual function assessments. Orbital magnetic resonance imaging (MRI) and computed tomography (CT) images were retrieved and labeled in 3D using multi-atlas label fusion. Based on the 3D structures, both traditional radiology measures (e.g., Barrett index, volumetric crowding index, optic nerve length) and novel volumetric metrics were computed. Using stepwise regression, the associations between structural metrics and visual field scores (visual acuity, functional acuity, visual field, functional field, and functional vision) were assessed. Across all models, the explained variance was reasonable (R2 ~ 0.1-0.2) but highly significant (p < 0.001). Instead of analyzing a specific pathology, this study aimed to analyze data across a variety of pathologies. This approach yielded a general model for the connection between orbital structural imaging biomarkers and visual function.


Remote synchronization of amplitudes across an experimental ring of non-linear oscillators.
In this paper, the emergence of remote synchronization in a ring of 32 unidirectionally coupled non-linear oscillators is reported. Each oscillator consists of 3 negative voltage gain stages connected in a loop to which two integrators are superimposed and receives input from its preceding neighbour via a "mixing" stage whose gains form the main system control parameters. Collective behaviour of the network is investigated numerically and experimentally, based on a custom-designed circuit board featuring 32 field-programmable analog arrays. A diverse set of synchronization patterns is observed depending on the control parameters. While phase synchronization ensues globally, albeit imperfectly, for certain control parameter values, amplitudes delineate subsets of non-adjacent but preferentially synchronized nodes; this cannot be trivially explained by synchronization paths along sequences of structurally connected nodes and is therefore interpreted as representing a form of remote synchronization. Complex topology of functional synchronization thus emerges from underlying elementary structural connectivity. In addition to the Kuramoto order parameter and cross-correlation coefficient, other synchronization measures are considered, and preliminary findings suggest that generalized synchronization may identify functional relationships across nodes otherwise not visible. Further work elucidating the mechanism underlying this observation of remote synchronization is necessary, to support which experimental data and board design materials have been made freely downloadable.


[Applied aspects of topographic-anatomical interrelations of female pelvic organs and cellular spaces].
The study of an autopsy material, obtained from females aged 15-74 years (145 organ complexes), using the classical anatomical research methods, resulted in the topographic-anatomical substantiation of transvaginal surgical accesses to subperitoneal and peritoneal pelvic floors taking into account the variants of the uterus position. The projection-syntopic correlations of subperitoneal and peritoneal structures with vaginal fornix were examined, the latter was divided for this purpose into the limited areas--vaginal segments. It was found that the transvaginal accesses in the uterus position of the anteversio-anteflexio and retroversio-retroflexio (with more common symmetrical rela tions between the pelvic structures and vaginal fornix), should be performed in the projection of vaginal segments 10.5-1.5 and 5.5-6.5. Due to asymmetric projection-syntopic relations of subperitoneal and peritoneal pelvic structures with vaginal fornix, the optimal accesses are recommended in the projection of vaginal segments 12-1.5, 11.5-2 and 6-6.5 in sinistroversio, sinistropositio with a clockwise uterine rotation, while in dextro-positio and counterclockwise uterine rotation, the accesses in the projection of vaginal segments 10.5-12, 10.5-1, 6-5.5 and 6-5 are preferable.


Characterization of African swine fever virion proteins j5R and j13L: immuno-localization in virus particles and assembly sites.
The j5R open reading frame (ORF) of the Malawi LIL 20/1 African swine fever virus (ASFV) isolate encodes a 111 amino acid protein with a putative transmembrane domain at the N terminus. Antisera raised against the predicted C-terminal peptide were used to identify the j5R protein by Western blotting in cells infected with ASFV or with recombinant vaccinia virus expressing the j5R ORF. This showed that the j5R protein migrates with an apparent molecular mass of 23-25 kDa, depending on the virus isolate, on SDS-PAGE and is expressed late during ASFV infection. The localization in infected cells and in virions of the j5R protein, and that of a previously characterized virion protein, j13L, which also contains a putative transmembrane domain, were studied by immunofluorescence and immuno-electron microscopy. Both proteins were expressed at 8-10 h post-infection (p.i.) as small multiple perinuclear foci which coalesced to a single area indicative of the virus factory at 18 h p.i. At the ultrastructural level j5R and j13L were detected mainly on membrane-like structures within the virus factory and on virus particles, suggesting that they may be involved in particle assembly. Negative contrast immuno-electron microscopy of mature extracellular virions confirmed that they are also integral structural proteins.


[Merkel cell carcinoma--clinically often misjudged].
Merkel cell carcinoma is a rare, rapidly growing, highly malignant dermal tumor which occurs preferentially on light-exposed skin in advanced age. The course of the disease is frequently characterized by the occurrence of lymph node metastases and local recurrences, even in the first year after removal of the primary tumour. The five-year overall survival rate is only about 65 %, despite rigorous therapy. The histological pattern is characterized by trabecular strands of small, uniform cells with large basophilic nuclei and typical neuroendocrine granules. The diagnosis is confirmed immunohistochemically by neuroendocrine and epithelial markers. The excision of the primary tumor is regarded as first-line therapy. Adjuvant radiatiotherapy is almost always indicated and should also include lymph node drainage. In the stage of nodal disease, a combination of excision and radiotherapy is recommended. Adjuvant chemotherapy can be applied in this stage, as in small-cell bronchial carcinoma. The prognostic advantage has, however, not been proven. Despite good response to radiatiotherapy and chemotherapy, with at least prolonged recurrence-free intervals, Merkel cell carcinoma is rarely curable at the distant metastasizing stage. Individually defined, aggressive treatment,including radiatiotherapy, may in future considerably improve the prognosis, especially in the early stages of the disease.


The GTPase stimulatory activities of the neurofibromatosis type 1 and the yeast IRA2 proteins are inhibited by arachidonic acid.
Three proteins, GTPase activating protein (GAP), neurofibromatosis 1 (NF1) and the yeast inhibitory regulator of the RAS-cAMP pathway (IRA2), have the ability to stimulate the GTPase activity of Ras proteins from higher animals or yeast. Previous studies indicate that certain lipids are able to inhibit this activity associated with the mammalian GAP protein. Inhibition of GAP would be expected to biologically activate Ras protein. In these studies arachidonic acid is shown also to inhibit the activity of the catalytic fragments of the other two proteins, mammalian NF1 and the yeast IRA2 proteins. In addition, phosphatidic acid (containing arachidonic and stearic acid) was inhibitory for the catalytic fragment of NF1 protein, but did not inhibit the catalytic fragments of GAP or IRA2 proteins. These observations emphasize the biochemical similarity of these proteins and provide support for the suggestion that lipids might play an important role in their biological control, and therefore also in the control of Ras activity and cellular proliferation.


Estimation of YKL-40 Acute-Phase Protein in Serum of Patients with Periodontal Disease and Healthy Individuals: A Clinical-Biochemical Study.
YKL-40, an acute-phase protein, is a novel potential inflammatory marker. It is a member of "mammalian chitinase-like proteins." YKL-40 is secreted by activated neutrophils and macrophages in both acute and chronic inflammation. It is also shown to be produced by vascular smooth muscle and endothelial cells, arthritic chondrocytes, cancer cells, and embryonic and fetal cells. It might play an important role in the initiation or maintenance of pro-inflammatory response. The purpose of the present study was to estimate the concentrations of YKL-40 in the serum of healthy and periodontally affected individuals. Serum samples were collected from forty patients of periodontally (Group C) affected sites (probing depth [PD] >5 mm) and gingivitis patients (Group B) affected sites (PD ≤ 3 mm) with bleeding on probing. Comparison with healthy controls was carried out by collecting serum samples from ten healthy volunteers (Group A). 5 ml of blood was collected from the antecubital fossa by venipuncture using a 20G needle with 5 ml syringe and immediately transferred to the laboratory. Serum was extracted from blood and stored at -70°C till the assay procedure, and enzyme-linked immunosorbent assay was performed to determine the concentrations of YKL-40. The mean YKL-40 concentration scores were significantly higher in Group C, i.e. 62.49 ± 8.33 when compared to Group B, i.e. 51.96 ± 4.30 and Group I, i.e. 44.23 ± 4.34, which was statistically significant (P ≤ 0.001). In the present study, mean probing pocket depth was higher in Group C than Group A (P ≤ 0.001). A positive correlation was found between probing pocket depth and concentrations of YKL-40 in serum (r = 0.815), P < 0.001, i.e. when the pocket depth increases, concentration of YKL-40 also increases. In this study the presence of YKL-40 in serum samples was observed both in healthy and chronic periodontitis. In this study, the concentration of YKL-40 was elevated in chronic periodontitis group when compared to healthy group. With increases in the amount of destruction, there is substantial increase in clinical parameter and YKL-40 concentration in serum, which is directly related to pocket depth. This study shows that YKL-40 is a novel biomarker for periodontal disease progression.