[Identification of susceptibility gene for pig umbilical hernia in different populations using transmission disequilibrium test].
A genome-wide scan for pig umbilical hernia (UH) was performed in a White Duroc × Erhualian resource population reported by our previously study, which detected two susceptibility microsatellite markers (SWR1928 on SSC7 and SW830 on SSC10) significantly affecting pig UH. Herein, fine mapping studies and identification of susceptibility genes for UH were performed in two different populations. A total of 40 SNPs in 12 positional candidate genes located on the two significant segments were genotyped in the F2/F3 resource population. Quality control of the genotype data and transmission disequilibrium test (TDT) were conducted using Plink v1.07 software. The results showed that g.708G>A in IL16 (interleukin 16) gene and g.10664G>A in CDC73 (cell division cycle 73) gene were significantly associated with pig UH. These two prominent SNPs and another two weakly associated SNPs g.10546A>G and g.10811A>G in CDC73 were also undergone the replication TDT test in the outbred commercial populations. All SNPs in the CDC73 gene were confirmed to be significantly associated with pig UH (P<0.05), including g. 10546A>G and g.10811A>G with extreme significant level (P<0.01). Based on these results, CDC73 should be a susceptibility gene for pig UH according to its biological functions and the molecular pathogenesis of UH.


The proto-oncogene LRF is under post-transcriptional control of MiR-20a: implications for senescence.
MicroRNAs (miRNAs) are short 20-22 nucleotide RNA molecules that act as negative regulators of gene expression via translational repression: they have been shown to play a role in development, proliferation, stress response, and apoptosis. The transcriptional regulator LRF (Leukemia/lymphoma Related Factor) has been shown to prevent p19ARF transcription and consequently to inhibit senescence in mouse embryonic fibroblasts (MEF). Here we report, for the first time, that LRF is post-transcriptionally regulated by miR-20a. Using a gene reporter assay, direct interaction of miR-20a with the LRF 3'UTR is demonstrated. To validate the interaction miR-20a/3'UTR LRF miR-20a was over-expressed, either by transient transfection or retroviral infection, in wild type mouse embryo fibroblasts and in LRF-null MEF derived from LRF knock-out mice. We observed LRF decrease, p19ARF increase, inhibition of cell proliferation and induction of senescence. The comparison of miR-20a activity in wt and LRF-null MEF indicates that LRF is the main mediator of the miR-20a-induced senescence and that other targets are cooperating. As LRF down-regulation/p19ARF induction is always accompanied by E2F1 down-regulation and increase of p16, we propose that all these events act in synergy to accomplish miR-20a-induced senescence in MEF. Senescence has been recently revaluated as a tumor suppressor mechanism, alternative to apoptosis; from this point of view the discovery of new physiological "senescence inducer" appears to be promising as this molecule could be used as anticancer drug.


Forecasting malaria incidence based on monthly case reports and environmental factors in Karuzi, Burundi, 1997-2003.
The objective of this work was to develop a model to predict malaria incidence in an area of unstable transmission by studying the association between environmental variables and disease dynamics. The study was carried out in Karuzi, a province in the Burundi highlands, using time series of monthly notifications of malaria cases from local health facilities, data from rain and temperature records, and the normalized difference vegetation index (NDVI). Using autoregressive integrated moving average (ARIMA) methodology, a model showing the relation between monthly notifications of malaria cases and the environmental variables was developed. The best forecasting model (R2adj = 82%, p < 0.0001 and 93% forecasting accuracy in the range +/- 4 cases per 100 inhabitants) included the NDVI, mean maximum temperature, rainfall and number of malaria cases in the preceding month. This model is a simple and useful tool for producing reasonably reliable forecasts of the malaria incidence rate in the study area.


Donovanosis With Bowen Disease.
A 45-year-old farmer presented with ulcers and plaques over his scrotum for the past 4 to 5 years. The condition started as a small lesion on the shaft of the penis, which improved with treatment; however, after 2 to 3 months, papulonodular lesions developed on the scrotum, which increased in size and subsequently broke down to form ulcers. He denied drug abuse but had a history of multiple unprotected sexual exposures. He was prescribed oral antibiotics, which improved the lesions, but he failed to take the antibiotics for more than a week. He also used powders, lotions, and salves (exact nature not known), which did not help and sometimes even burned the skin. After stopping the medicine, he developed new lesions that followed a similar course. Examination revealed nontender ulcers on the scrotum with raised, rolled-out margins and pale red, granulation tissue that bled on touch (Figure 1). In addition, there were nodules with a pinkish red granular surface and scaly erythematous plaques on the scrotum. Regional lymph nodes were not enlarged.


Sensitivity of upper airway reflexes in cigarette smokers: effect of abstinence.
In two studies we have compared the upper airway reflex sensitivity (UARS) of chronic cigarette smokers with that of non-smokers and also the effect of different periods of abstinence on UARS in the smoking groups. UARS was measured by recording the threshold concentration of dilute ammonia vapour required to stimulate reflex glottic closure. The first study compared UARS in 20 non-smokers with 20 smokers, followed by another measurement in the smoking group after 24 h of abstinence. In study two, we measured UARS repeatedly over a period of 3-4 weeks in 16 smokers, half of whom had stopped smoking on day 0. Chronic cigarette smokers were found to have significantly greater UARS compared with non-smokers; the sensitivity was unaltered after 24 h of abstinence but was found to reduce over several days, the change commencing between 24 and 48 h, with most achieving a consistent change within 10 days.


Evaluation of computer-assisted instruction versus traditional new-employee training.
Personnel time and costs associated with computer-assisted instruction (CAI) and traditional "one-on-one" instruction in basic computer drug-order entry procedures were compared. Both programs consisted of an introduction to the training session, familiarization of users with the computer hardware and keyboard, and step-by-step instructions in unit dose and intravenous admixture order-entry procedures. The CAI module was developed by a pharmacist with no prior programming experience. It was designed to be used side-by-side with the actual inpatient pharmacy computer system. Fifth-year pharmacy students in their clinical clerkship rotation served as the study population. The personnel (both subject and pharmacy supervisor) time and costs associated with each method were evaluated for significant differences by a two-tailed Student's t test. Of 21 subjects who participated in this study, 11 received CAI and 10 received traditional instruction. CAI was associated with significantly less mean total personnel time (99.64 +/- 18.78 minutes) than one-on-one instruction (133.60 +/- 22.89 minutes). Mean total salary expense was significantly lower for CAI ($13.03 +/- 2.15) than for one-on-one instruction ($28.79 +/- 4.91). Program development time for the CAI module was 18.5 hours longer than that for the one-on-one program. The CAI module cost $1577.77 more to develop than the one-on-one program; however, 24 new employees would be required to offset development costs if the hardware were already available and 100 new employees if hardware had to be purchased. Computer-assisted instruction of new employees in computer order-entry procedures can be a cost-effective alternative to traditional training methods.(ABSTRACT TRUNCATED AT 250 WORDS)


Feasibility of coronal views in computed scanning of the head.
With some models of computerized scanners, it is possible to obtain not only axial, but also coronal tomograms. This is feasible because a water bag is not used and limited tilting capacity is built into the gantry. The head is extended and the central ray directed perpendicularly to the base of the skull. The resulting views, orthogonal to the conventional axial views, furnish important complementary information.


TNFα polymorphism as marker of immunosenescence for rheumatoid arthritis patients.
Expansion of CD4(+)CD28(null), a common feature of immunosenescence, which has been reported in rheumatoid arthritis (RA) patients, may also be associated with a CD4(+) imbalance. Although the increase of CD4(+)CD28(null) cells has been related to TNFα exposure, nothing is known about the possible role of genetic variants of this cytokine. Participants were genotyped for TNFA rs1800629 (-308 G>A) and frequency of the CD4(+)CD28(null), regulatory T cells and Th1 cells subsets were quantified in peripheral blood samples by flow cytometry in 129 RA patients and 33 healthy controls. The expansion of CD4(+)CD28(null) cells in RA patients was associated with TNFA genotype, even at diagnosis, and linked to markers of aggressive disease in patient carriers of the minor allele. Analysis of regulatory T cells and IFNγ-CD4(+) expression suggested that defective suppression and/or Th1-shift could underlie the expansion of this population in these patients. Finally, although treatment with TNFα-blockers reduced CD4(+)CD28(null) cells in most patients, only those carriers of the common GG genotype reached values within the range of HC and showed a disease activity improvement correlated to this decrease. Our results provide evidence for a genetic basis of the premature immunosenescence of RA patients and highlight its potential role in clinical outcome after TNFα blockade.


The prevalence and special educational requirements of dyscompetent physicians.
Underperformance among physicians is not well studied or defined; yet, the identification and remediation of physicians who are not performing up to acceptable standards is central to quality care and patient safety. Methods for estimating the prevalence of dyscompetence include evaluating available data on medical errors, malpractice claims, disciplinary actions, quality control studies, medical record review studies, and in-stream assessments of physician performance. These data provide a range of estimates from 0.6% to 50%, depending on the method. A reasonable estimate of dyscompetence appears to be 6% to 12%. Age-related cognitive decline, impairment due to substance use disorders, and other psychiatric illness can contribute to underperformance, diminishing physicians' insight into their level of performance as well as their ability to benefit from an educational experience.Currently, dyscompetent physicians in the United States are identified through either the legal system or peer review. The primary method of resolving issues of underperformance in physicians is through continuing medical education (CME). Although a number of specialized assessment and education programs exist in the United States, these programs are largely underutilized. Similar programs exist in Canada and have provided evidence of the efficacy of a more specialized and individualized educational approach for underperforming physicians. Current specialty programs focused on this population employ individual assessments of knowledge and performance, individually designed educational programs, long-term plans for maintenance of educational activity, and repeated assessment of performance level. Noting that few CME programs offer these requirements, a number of changes to current medical quality assurance programs that might foster such educational requirements for underperforming physicians are provided.


NEURO multimedial data base and management system for neuropathology.
Implementation of multimedial data base and management system for cytological, biopsy, immunological, electronmicroscopy and autopsy examinations are described. Packet NEURO was implemented on IBM compatible computers runs under NetWare network system. The packet allows to realize all basic data base operations such as: entering, search, replace and deleting of records. Adding new records uses operations of projection, selection and merging relations include the formalized and coded SNOMed topography and morphology fields. The description fields, macro- and microscopic images are collecting and managing.


Dietary pattern and oral cancer risk--a factor analysis study.
The role of diet in cancer risk has mainly been investigated based on intake of individual food items. However, food consumption is made up of a combination of various food items. This study aims to determine the association of dietary patterns with oral cancer risk. A total of 306 matched cases and controls were recruited in this study. Data on dietary intake were obtained using food frequency questionnaire (FFQ). Factor analysis (FA) was performed to identify dietary patterns based on the intake of nine major food groups, resulting in four factors/components being retained. The odds ratio (OR) was computed for each component using conditional logistic regression. The first pattern labelled as 'modern' was loaded with processed foods and snacks, whereas the second pattern termed as 'prudent' was characterized by intake of fruits and vegetables. The third pattern labelled as 'traditional' consisted of beverages and starches, while the fourth pattern termed as 'combination' was loaded with intakes of dairy, fermented/salted and meat/by-products. A significant reduced risk was found for 'prudent' (OR 0.53, 95% CI = 0.28-0.98), whereas an increased risk was found for both 'combination' (OR 2.43, 95% CI = 1.33-4.45) and 'traditional' (OR 2.32, 95% CI = 1.23-4.25) patterns. However, after adjusting for risk habits of tobacco smoking, alcohol consumption and betel quid chewing, only 'combination' (aOR 2.99, 95% CI = 1.55-5.75) and 'traditional' (aOR 2.08, 95% CI = 1.09-3.97) patterns remained significant. Consumption in the highest tertile of 'traditional' and 'combination' patterns may induce twice and thrice the risk of oral cancer, respectively.


Nickel Nanoparticles Immobilized over Mesoporous SBA-15 for Efficient Carbonylative Coupling Reactions Utilizing CO2: A Spotlight.
Ecofriendly routes for the synthesis of carbamates and carbonylative coupling products such as benzyl formate derivatives are very demanding for both academia and industries. Foreseeing a sustainable green future, we systematically analyzed the synthesis history of both these chemicals, mentioning their pros and cons. As a step towards green chemistry, here we have optimized the reaction conditions for the synthesis of various benzyl formates from corresponding benzyl halides and carbamates from substituted anilines and alkyl halides catalyzed by Ni(0) nanoparticles (NPs) immobilized over amine-functionalized ordered mesoporous SBA-15 material in the presence of CO2 as C1 source. This spotlight on applications is aimed to provide a clear outlook to date regarding the gradual progress in the synthesis of both these aforementioned chemicals and finally addresses further efforts for overcoming the current challenges.


Impact of a heart failure multidisciplinary clinic on the reduction of healthcare-related events and costs: the GEstIC study.
Heart failure (HF) is the leading cause of hospitalization in the elderly in developed countries and significantly impacts public health expenditures. Patients with HF usually have associated comorbidities that require multidisciplinary management. This study aims to demonstrate the benefits of a multidisciplinary clinic in reducing all-cause hospitalizations and HF events (HF hospitalizations and urgent HF visits) in a real-world setting. Finally, the study evaluates the associated costs of HF events. This observational study included patients admitted to GEstIC, a multidisciplinary Portuguese HF clinic, from January 2013 to February 2019, who had one-year follow-up. Hospitalizations and HF events, total days spent in the hospital during HF hospitalizations, and HF events-related costs, in the year before and the year after GEstIC admission, were compared. Of the 487 patients admitted to the GEstIC, 287 were eligible for the study sample. After one year of HF patients' multidisciplinary management at GEstIC, there was a 53.7% reduction in all-cause hospitalizations (462 vs. 214), a 71.7% reduction in HF hospitalizations (392 vs. 111), and a 39.1% reduction in urgent HF visits (87 vs. 53). As a result, there was a significant decrease of 12.6 days in the length of hospital stay due to HF per patient (15.6 vs. 3.0, p < 0.001). This translated into the release of 9.9 hospital beds in the year following admission to GEstIC. The average total savings associated with the reduction of HF events was €5,439.77 per patient (6,774.15 vs. 1,334.38, p < 0.001), representing a total cost reduction of €1,561,213. Furthermore, the significant reduction in the number of all events was independent of the patient's left ventricular ejection fraction (LVEF). Significant reductions in all-cause and HF hospitalizations and urgent HF visits were observed with the implementation of this multidisciplinary clinic for HF patients' management. This was particularly important for patients with LVEF >40%. Before GEstIC, there was no medical intervention to improve the prognosis of these patients. The reduction of over one million euros in health-related costs after only one year of person-centered multidisciplinary management highlights the need to replicate this approach in other national healthcare institutions.


The role of education in child and adolescent marriage in rural lowland Nepal.
Marriage during childhood and adolescence adversely affects maternal and child health and well-being, making it a critical global health issue. Analysis of factors associated with women marrying ≥18 years has limited utility in societies where the norm is to marry substantially earlier. This paper investigated how much education Nepali women needed to delay marriage across the range of ages from 15 to ≥18 years. Data on 6,406 women aged 23-30 years were analysed from the Low Birth Weight South Asia Trial on the early-marrying and low-educated Maithili-speaking Madhesi population in Terai, Nepal. Multivariable logistic regression models assessed the associations of women's education with marrying aged ≥15, ≥16, ≥17 and ≥18 years. Cox proportional hazards regression models quantified the hazard of marrying. Models adjusted for caste affiliation. Women married at median age of 15 years and three-quarters were uneducated. Women's primary and lower-secondary education were weakly associated with delaying marriage, whether the cut-off to define early marriage was 15, 16, 17 or 18 years, with stronger associations for secondary education. Caste associations were weak. Overall, models explained relatively little of the variance in the likelihood of marriage at different ages. The joint effects of lower-secondary and higher caste affiliation and of secondary/higher education and mid and higher caste affiliation reduced the hazard of marrying. In early-marrying and low-educated societies, changing caste-based norms are unlikely to delay women's marriage. Research on broader risk factors and norms that are more relevant for delaying marriage in these contexts is needed. Gradual increases in women's median marriage age and increased secondary education may, over time, reduce child and adolescent marriage.


[Clinical study of postoperative infection of gastrointestinal cancer. Randomized study of preventive efficacy of cefmetazole versus cephalothin in postoperative infection of gastric and colorectal cancer].
Effectiveness of prophylactic administration of cefmetazole (CMZ) (A) for postoperative infection was compared with that of cephalothin (B) using patients undergoing resection of gastric cancers or colorectal cancers as subjects in cooperation with 19 major hospitals in the Tohoku districts. Using the envelope method, each hospital allocated, at random, patients with each organ removed into groups A and B. Either drug was administrated at 4 g/day (in 2 divided doses) for 7 days. Registered patients with gastric cancers amounted to 114 in group A and 113 in group B; those with colorectal cancers were 63 each in groups A and B. As to background factors, advanced cancers were found more in group A with gastric cancers, and operations took more time on the average in this group; however, there were no significant differences in other factors between the 2 groups with gastric cancers and in the all factors between A and B groups with colorectal cancers. Rates of ineffective prophylaxis judged by physicians in charge were 3.9% and 21.0%, respectively, in groups A and B with gastric cancers, and 5.0% and 20.7%, respectively, in groups A and B with colorectal cancers. Rates of ineffective prophylaxis determined by committees were 16.7% and 31.0% among the former, and 8.3% and 29.3% among the latter, respectively. Ineffectiveness rates in group A with gastric cancers or colorectal cancers were significantly lower in all the evaluations, and CMZ was, therefore, comfirmed to have stronger efficacy.


C-reactive Protein Is a Predictor of Prognosis of Prostate Cancer: A Systematic Review and Meta-Analysis.
Increasing evidence suggested that inflammation is associated with the pathogenesis and progression of several solid tumors. This study was conducted to explore the association between C-reactive protein (CRP) and survival of prostate cancer (PCa). An electronic search was completed on the basis of PubMed, Embase and Cochrane Central Register of Controlled Trials. The hazard ratio (HR) and 95% confidence interval (CI) were extracted. Studies evaluating the relation between pretreatment levels of CRP and survival of PCa were included. Sixteen articles incorporating 17,833 patients were eligible for the present meta-analysis. Elevated pretreatment CRP level was significantly associated with poorer overall survival (OS) (HR=1.58, 95% CI 1.31-1.91, P<0.001), cancer-specific survival (CSS) (HR=1.83, 95% CI 1.19-2.80, P=0.006), progression-free survival (PFS) (HR=1.64, 95%CI 1.03-2.61, P=0.036), and biochemical-recurrence free survival (BC-RFS) (HR=1.29, 95% CI 1.11-1.51, P=0.001). Elevated pretreatment serum CRP level is strongly correlated with worse prognosis in patients with PCa, including OS, CSS, PFS and BC-RFS.


MUSE: clinical experience.
In the UK, an estimated 17-19% of men suffer from erectile dysfunction (ED). Until the introduction of sildenafil, the medical treatment of ED mainly depended on intracavernosal injections. The introduction of MUSE has generated interest, since it obviates the use of 'needles'. MUSE is an intra-urethral method of alprostadil (prostaglandin E1 analogue) administration. We investigated the safety and efficacy of MUSE in 100 patients. After confirming the diagnosis of ED, treatment was started with MUSE. Once we were satisfied that the patients could self-administer MUSE, they were discharged from our clinic. They were contacted six months later and asked to complete a questionnaire. Only 35% of the 100 patients (aged 46-73 years) with ED of mixed aetiology were initially successfully treated with MUSE. All but two of them needed 1,000 microg. After six months, only 43% of these initially successfully treated patients continued to use MUSE; of these, 33% only found it effective on every third occasion, or worse. The remaining 57% of the initially successfully treated patients stopped taking MUSE because it was no longer effective or it caused side-effects (such as urethral bleeding and/or irritation). MUSE, in our experience, is moderately effective in treating ED. However, MUSE is an alternative in some patients with ED who do not respond to other treatments or where these options are contraindicated. Owing to the high dropout rate, patients treated with MUSE should be followed-up closely.


Metastasis of hepatocellular carcinoma to the proximal jejunum manifested by occult gastrointestinal bleeding.
A 31-yr-old man, who had received left hepatic lobectomy for a ruptured hepatocellular carcinoma 17 months previously, began to have elevation of serum alpha-fetoprotein and occult gastrointestinal bleeding. Abdominal computed tomography, angiography, ultrasonography, upper gastrointestinal panendoscopy, colon-fiberscopy and endoscopic retrograde cholangiopancreaticography failed to disclose any recurrent intrahepatic tumor or bleeder in the gastrointestinal tract. However, a barium meal study revealed an intussusception with a suspicious nodular lesion in the proximal jejunum as the leading edge, which, after laparotomy, was proven to be a metastatic hepatocellular carcinoma and the cause of the gastrointestinal bleeding. The serosal side of this lesion was free from cancer involvement and there was no peritoneal implantation or lymph node involvement. The metastasis is probably hematogenous. The extremely unusual location involved by hepatocellular carcinoma in this patient signifies the ubiquitous nature of metastasis in this cancer.


Two new species of the genus Metaxonchium Coomans Nair, 1975 (Nematoda, Dorylaimida, Belondiridae) from Vietnam.
Two new species of the genus Metaxonchium are described from natural habitats of Vietnam. Metaxonchium bonkowskii sp. n. is characterized by its 1.69-2.23 mm long body, lip region offset by weak constriction and 9.5-10.5 µm broad, odontostyle 11-13 µm long, neck 673-868 µm long with the pharyngeal expansion occupying 66-77% of its length, anterior genital branch reduced to a uterine sac 75-135 µm long or 4-7% of body length, posterior uterus tetrapartite and including a Z-like differentiation, V = 51-55, and female tail short and rounded (37-51 µm, c = 66-97, c' = 0.5-0.7). Metaxonchium silvaticum sp. n is characterized by its 1.28-1.43 mm long body, lip region offset by weak depression and 7.0 µm broad, odontostyle 8-9 µm long, neck 502-630 µm long with the pharyngeal expansion occupying 65-76% of its length, anterior genital branch reduced to a uterine sac 65-80 µm long or 4-6% of body length, posterior uterus tripartite, non-echinophor, V = 52-57, tail short and rounded (18-23 µm, c = 56-74, c' = 0.6-0.8) with abundant blister-like or saccate bodies, spicules 41 µm long, and seven spaced ventromedian supplements.


Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats.
The present study was designed to investigate the hypoglycemic and hypolipidemic properties of an ethanolic extract of Cichorium intybus (CIE) which is widely used in India as a traditional treatment for diabetes mellitus. Male Sprague-Dawley rats aged 9 weeks (160-200 g) were administered with streptozotocin (STZ, 50mg/kg) intraperitoneally to induce experimental diabetes. The Cichorium intybus whole plant was exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and freeze dried to get powder. Hypoglycemic effects of CIE were observed in an oral glucose tolerance test (OGTT) in which, a dose of 125 mg of plant extract/kg body weight exhibited the most potent hypoglycemic effect. Moreover, daily administration of CIE (125 mg/kg) for 14 days to diabetic rats attenuated serum glucose by 20%, triglycerides by 91% and total cholesterol by 16%. However, there was no change in serum insulin levels, which ruled out the possibility that CIE induces insulin secretion from pancreatic beta-cells. In addition, hepatic glucose-6-phosphatase activity (Glc-6-Pase) was markedly reduced by CIE when compared to the control group. The reduction in the hepatic Glc-6-Pase activity could decrease hepatic glucose production, which in turn results in lower concentration of blood glucose in CIE-treated diabetic rats. In conclusion, our results support the traditional belief that Cichorium intybus could ameliorate diabetic state.


Behavioral management of specific pathogen-free rhesus macaques: group formation, reproduction, and parental competence.
Breeding colonies of specific pathogen-free (SPF) rhesus macaques were established to eradicate the transmission of Herpesvirus simiae and several retroviruses in this species. Strategies to attain this goal included the combination of large numbers of monkeys into groups, the establishment of small unimale groups, and a program using animals that were temporarily socially restricted. All methods required the establishment of new social groups from unfamiliar animals. In using these methods, we encountered important behavioral questions related to the group formation process, as well as reproductive and parental competence. Age and prior social experience were important determinants of social and parental success. New multimale-multifemale SPF group formations were successful initially and involved the least aggression during the first breeding season when young females and older males were used. Formation of unimale groups was successful, even when males and females were of similar ages. Breeding competence did not seem to be affected by any of the SPF colony management procedures, but animals with restricted early social experience exhibited impaired parental competence when compared with animals with more social experience. Males were more sensitive to the effects of early social restriction than females. A variety of behavioral obstacles will be encountered when attempting to establish an SPF breeding colony by forming groups by use of these methods. Skilled behavioral management is necessary to surmount these obstacles and to achieve satisfactory social integration, reproduction, and parenting.


Construction of selenium nanoparticles/β-glucan composites for enhancement of the antitumor activity.
We report on a green procedure for the stabilization of selenium nanoparticles (SeNPs) by a naturally occurring β-glucan with triple helical conformation known as Lentinan (t-LNT) in water after denaturing into single chains (s-LNT) at 140 °C. The results demonstrated that the s-LNT can interact with SeNPs through Se-O-H interaction. Transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectra, UV/vis, X-ray diffraction (XRD) and dynamic light scattering (DLS) showed that s-LNT coated SeNPs to form a stable nano-composite Se/s-LNT, leading to good dispersion of SeNPs. Especially, the as-prepared Se/s-LNT composite in the solution could remain homogeneous and translucent for 30 days without any precipitates. Different size distribution of SeNPs was prepared by simply controlling the concentrations of selenite sodium and the corresponding reducing agent ascorbic acid. The size effect of SeNPs on anti-tumor activity was revealed that the SeNPs with more evenly particle size distribution show the higher anticancer activity.


Effects of spontaneous chronic hypoglycemia on central and peripheral nervous system in insulinoma patients before and after surgery: a neurophysiological follow-up.
To investigate the effects of spontaneous chronic hypoglycemia on the peripheral and central nervous system, a multimodal neurophysiological evaluation [median somatosensory (mSEP), brain stem auditory (BAEP), and visual (VEP) evoked potentials recordings] was performed in seven insulinoma patients before and 3 and 6 months after surgical removal of tumor. Before surgery, mSEP findings showed abnormal reduction in peripheral wrist-Erb conduction velocity in three patients as well as a pathological increase in Erb-N13, N13-N20, and Erb-N20 conduction times in five cases. BAEP and VEP recordings gave pathological results in two patients. Moreover, during hypoglycemia, the III-V and I-V interpeak latencies of BAEPs were significantly prolonged (P < 0.01 and P < 0.005, respectively) compared to recordings in euglycemia. After 6 months, a mSEP recovery, even if partial was noted in four patients, BAEPs were normalized in one case, and VEPs were unmodified. Compared to presurgery data, these recordings showed a significant (P < 0.05), but incomplete, shortening of BAEPs (III-V and I-V interpeak latencies) and mSEPs (Erb-N13 and Erb-N20 conduction times). Our findings demonstrate that multiple and selective neurophysiological abnormalities are present in insulinoma patients, confirm that hypoglycemia impairs suddenly brain stem function, and show that after tumor removal, long recovery times for improvement of some neurophysiological anomalies are requested.


Biological variations of lysozyme concentration in the tear fluids of healthy persons.
Concentration of tear lysozyme was measured in healthy Indian subjects of the same racial group aged 2 to 78 years by a single radial immunodiffusion technique. Variations in its concentration between the two eyes, during the day, over a period of time, in both sexes, and in different age groups were studied. The diurnal and age-related changes in the concentration of tear lysozyme were found to vary to an appreciable extent. The mean lysozyme concentration in tears was lower in the morning and higher in the evening. It tended to be low in children under 16, rose and attained a plateau in the age group 16-45 years and fell in later life, though still remaining higher than in the children.


Skin typing for assessment of skin cancer risk and acute response to UV-B and oral methoxsalen photochemotherapy.
Skin typing is a clinical classification system based on a patient's historical reporting of the acute skin response to sunlight. It is advocated as a means of determining an individual's relative risk of skin tumors and has been used to determine the initial therapeutic dose of UV radiation for UV-B phototherapy or oral methoxsalen photochemotherapy (PUVA) for psoriasis. Among PUVA-treated patients, the relative risk of cutaneous carcinoma was significantly higher among patients with skin types I and II compared with patients with skin type IV (3.2 and 2.3, respectively). Skin type was a better predictor of this risk than eye or hair color. The minimal erythemal dose ( MErD ) and minimal phototoxic dose (MPD) increased with increasing skin type number, but within a given skin type each varied as much as sixfold. Skin type was a good clinical predictor of skin cancer risk, but lacked specificity as a predictor of an individual's MErD or MPD.


An Odontogenic Keratocyst in the Temporal Region.
The authors report a very rare patient with ectopic odontogenic keratocyst (OKC) in the temporal region that is distant form the mandible. Based on the interesting report, they discuss about the possible origin and illustrate the development of the ectopic OKC. It shows that the OKC could distally relapse with the help of temporal muscle. The surgeon should be more proactive to deal with the peripheral muscle of lesion.


Boronic Acid Modifications Enhance the Anti-Influenza A Virus Activities of Novel Quindoline Derivatives.
The unique glycan-binding ability of chemically synthesized boronic acid derivatives makes them emerging candidates for developing anti-influenza A virus (IAV) drugs. Herein we report the synthesis and the anti-IAV activities of three series of novel boronic acid-modified quindoline derivatives both in vitro and in vivo. Boronic acid-modified compounds 6a and 7a effectively prevented the entry of virus RNP into the nucleus, reduced virus titers in IAV infected cells, and also inhibited the activity of viral neuraminidase. Compound 7a possessed broad antiviral spectrum and was able to inhibit cellular NF-κB and MAPK signaling pathways to block IAV infection. More importantly, IAV infected mice treated with compound 7a showed better survival rates than mice treated with oseltamivir, a popular anti-IAV drug. Thus, our study provides not only an antiviral preclinical candidate but also useful information for further research and development of boronic acid-modified anti-IAV drugs.


High-resolution heteronuclear multidimensional NMR of proteins in living insect cells using a baculovirus protein expression system.
Recent developments in in-cell NMR techniques have allowed us to study proteins in detail inside living eukaryotic cells. In order to complement the existing protocols, and to extend the range of possible applications, we introduce a novel approach for observing in-cell NMR spectra using the sf9 cell/baculovirus system. High-resolution 2D (1)H-(15)N correlation spectra were observed for four model proteins expressed in sf9 cells. Furthermore, 3D triple-resonance NMR spectra of the Streptococcus protein G B1 domain were observed in sf9 cells by using nonlinear sampling to overcome the short lifetime of the samples and the low abundance of the labeled protein. The data were processed with a quantitative maximum entropy algorithm. These were assigned ab initio, yielding approximately 80% of the expected backbone NMR resonances. Well-resolved NOE cross peaks could be identified in the 3D (15)N-separated NOESY spectrum, suggesting that structural analysis of this size of protein will be feasible in sf9 cells.


Myocardial structural changes in long-term human severe sepsis/septic shock may be responsible for cardiac dysfunction.
The present investigation sought to determine the cellular mechanisms directly dependent on long-term severe sepsis/septic shock that could lead to myocardial structural changes in humans. Human hearts from eight cases of long-term severe sepsis/septic shock arising from infection, as defined by the ACCP/SCCM Consensus Conference; eight cases of acute necrotizing pancreatitis and acute lung injury, a noninfectious pathologic cause of systemic inflammatory response; and three cases of accidental death without thoracic injury selected from autopsies were studied. Transmural blocks of myocardial tissue were excised from the middle portion of the left ventricular free wall and were fixed in formalin or were frozen. Histochemical and immunohistochemical methods were used to evaluate the cross-striations of the myocardial cells, the number and size of interstitial macrophages, the intracardiomyocyte accumulation of lipid, the actin/myosin contractile apparatus, and the expression of iNOS, nitrotyrosine, and TNF-alpha in the myocardia of septic and control hearts. Greater interstitial cellular infiltration composed of larger and elongated macrophages and TNF-alpha protein expression in myofibers, interstitial macrophage cell types, and smooth muscle cells and endothelial cell in the vessels; intracardiomyocyte lipid accumulation; scattered foci of actin/myosin contractile apparatus disruption; and increased expression for iNOS and nitrotyrosine in myocytes and interstitial macrophage cell types could be observed in long-term human septic myocardium as compared with normal and acute pancreatitis control myocardia. These findings give support to an opinion that structural changes could be responsible for long-term sepsis-induced myocardial dysfunction. The higher number of macrophages, most of them with morphological features of "activation," and TNF-alpha protein expression could favor the reduction of cardiac function in septic hearts. The intramyocyte lipid accumulation in these hearts very likely reflects myocardium ventricular contractile dysfunction. In addition, the increased expression of iNOS and the evidence for the significant presence of peroxynitrite in cardiomyocytes and interstitial macrophage cell types suggest that oxidative damage may play a role in actin/myosin disruption in the hearts of septic patients.


Behavioral Variant of Frontotemporal Dementia and Homicide in a Historical Case.
Criminal behavior is a clinical feature of the behavioral variant of frontotemporal dementia (bvFTD), ranging from socially inappropriate behavior and minor offenses (such as shoplifting, driving-related violations, housebreaking, trespassing) to the more extreme acts of sex crimes and violence. To our knowledge, no homicide case involving bvFTD is well illustrated in the scientific literature, and only a few anecdotal annotations are available about bvFTD and homicide. This is surprising considering the inclination of individuals with bvFTD to lack impulse control, to manifest disinhibition, to display diminished emotional awareness and loss of empathy, and to show behavior indicative of disordered moral reasoning. Here, we describe the 19th-century homicide case of Benjamin Reynaud, a man whose clinical characteristics suggest the bvFTD diagnosis. Reynaud's case may represent a rare instance of homicide committed by an individual with bvFTD and provide a basis for some reflections regarding the relationship between homicidal behavior and bvFTD.


Sphingosine-1-Phosphate Prevents Egress of Hematopoietic Stem Cells From Liver to Reduce Fibrosis.
There is growing interest in the use of bone marrow cells to treat liver fibrosis, however, little is known about their antifibrotic efficacy or the identity of their effector cell(s). Sphingosine-1-phosphate (S1P) mediates egress of immune cells from the lymphoid organs into the lymphatic vessels; we investigated its role in the response of hematopoietic stem cells (HSCs) to liver fibrosis in mice. Purified (c-kit+/sca1+/lin-) HSCs were infused repeatedly into mice undergoing fibrotic liver injury. Chronic liver injury was induced in BoyJ mice by injection of carbon tetrachloride (CCl4) or placement on a methionine-choline-deficient diet. Some mice were irradiated and given transplants of bone marrow cells from C57BL6 mice, with or without the S1P antagonist FTY720; we then studied HSC mobilization and localization. Migration of HSC lines was quantified in Transwell assays. Levels of S1P in liver, bone marrow, and lymph fluid were measured using an enzyme-linked immunosorbent assay. Liver tissues were collected and analyzed by immunohistochemical quantitative polymerase chain reaction and sphingosine kinase activity assays. We performed quantitative polymerase chain reaction analyses of the expression of sphingosine kinase 1 and 2, sphingosine-1-phosphate lyase 1, and sphingosine-1-phosphate phosphatase 1 in normal human liver and cirrhotic liver from patients with alcohol-related liver disease (n = 6). Infusions of HSCs into mice with liver injury reduced liver scarring based on picrosirius red staining (49.7% reduction in mice given HSCs vs control mice; P < .001), and hepatic hydroxyproline content (328 mg/g in mice given HSCs vs 428 mg/g in control mice; P < .01). HSC infusion also reduced hepatic expression of α-smooth muscle actin (0.19 ± 0.007-fold compared with controls; P < .0001) and collagen type I α 1 chain (0.29 ± 0.17-fold compared with controls; P < .0001). These antifibrotic effects were maintained with infusion of lymphoid progenitors that lack myeloid potential and were associated with increased numbers of recipient neutrophils and macrophages in liver. In studies of HSC cell lines, we found HSCs to recruit monocytes, and this process to require C-C motif chemokine receptor 2. In fibrotic liver tissue from mice and patients, hepatic S1P levels increased owing to increased hepatic sphingosine kinase-1 expression, which contributed to a reduced liver:lymph S1P gradient and limited HSC egress from the liver. Mice given the S1P antagonist (FTY720) with HSCs had increased hepatic retention of HSCs (1697 ± 247 cells in mice given FTY720 vs 982 ± 110 cells in controls; P < .05), and further reductions in fibrosis. In studies of mice with chronic liver injury, we showed the antifibrotic effects of repeated infusions of purified HSCs. We found that HSCs promote recruitment of endogenous macrophages and neutrophils. Strategies to reduce SIP signaling and increase retention of HSCs in the liver could increase their antifibrotic activities and be developed for treatment of patients with liver fibrosis.


Genome-wide association study reveals the genetic basis of brace root angle and diameter in maize.
Brace roots are the main organ to support the above-ground part of maize plant. It involves in plant growth and development by water absorption and lodging resistance. The bracing root angle (BRA) and diameter (BRD) are important components of brace root traits. Illuminating the genetic basis of BRA and BRD will contribute the improvement for mechanized harvest and increasing production. A GWAS of BRA and BRD was conducted using an associated panel composed of 508 inbred lines of maize. The broad-sense heritability of BRA and BRD was estimated to be respectively 71% ± 0.19 and 52% ± 0.14. The phenotypic variation of BRA and BRD in the non-stiff stalk subgroup (NSS) and the stiff stalk subgroup (SS) subgroups are significantly higher than that in the tropical/subtropical subgroup (TST) subgroups. In addition, BRA and BRD are significantly positive with plant height (PH), ear length (EL), and kernel number per row (KNPR). GWAS revealed 27 candidate genes within the threshold of p < 1.84 × 10-6 by both MLM and BLINK models. Among them, three genes, GRMZM2G174736, GRMZM2G445169 and GRMZM2G479243 were involved in cell wall function, and GRMZM2G038073 encoded the NAC transcription factor family proteins. These results provide theoretical support for clarifying the genetic basis of brace roots traits.


Mitral valvar regurgitation in a child with Sweet's syndrome.
We report the very unusual perforation of the mitral valve in the setting of Sweet's syndrome, or acute febrile neutrophilic dermatosis, in a boy aged 5 years. Surgical repair was uneventful, and follow-up showed no residual anomalies. Acute or delayed valvitis, with damage to either the mitral or aortic valves, should be screened for in this rare disease.


[Relationship between the mandibular hypoplasia and temporomandibular joint internal derangement in adolescents with skeletal class Ⅱ malocclusion].
Mandibular hypoplasia is very common clinically. Studies have reported that temporomandibular joint internal derangement (TMJID) might manifest as mandibular retrusion, and whether there is a direct correlation between them remains controversial in academia. On the other hand, for adolescent patients with skeletal class Ⅱ malocclusion, the growth of mandible could be motivated by orthopedic force, and then the mandibular retrusion corrected. However, if TMJID is the direct cause of mandibular retrusion, orthopedic treatment will not have a significant effect on it. Base on literature review and analysis as well as our own research, this article will review the distribution of structural abnormalities of the temporomandibular joint in adolescents with mandibular hypoplasia and its association with skeletal class Ⅱ malocclusion, as well as the effect of TMJID on the treatment of skeletal class Ⅱ malocclusion in adolescents.


Drug-induced hypoglycaemia in type 2 diabetes.
Hypoglycaemia is a side effect caused by some therapies for type 2 diabetes, which can cause physical, social and psychological harm. Hypoglycaemia also prevents attainment of treatment goals and satisfactory glycaemic control. The risk of hypoglycaemia associated with commonly prescribed therapies, including metformin, sulphonylureas, dipeptidyl peptidase-4 enzyme (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists and thiazolidinediones, is reviewed in this paper (insulin-induced hypoglycaemia is not included). Other medications that are frequently co-prescribed in type 2 diabetes are also discussed, including anti-hypertensive drugs, antibiotics and fibrates, along with various important patient-related risk factors. Hypoglycaemia is a common and potentially dangerous side effect of some medications used for type 2 diabetes. The risk of hypoglycaemia should always be considered when selecting and implementing a therapy, with a focus on the individual. Future research into new therapies should measure the frequency of hypoglycaemia prospectively and accurately. Hypoglycaemia has been shown to be a potentially life-threatening metabolic stress; therefore therapies that effectively manage diabetes without the risk of hypoglycaemia are likely to be favoured in the future.


Cysts of the third ventricle.
Cysts of the third ventricle, predominantly being of congenital origin, are often summarized under the heading of ependymal or neuroepithelial cysts, if they contain an epithelial covering. Though surely they form a heterogeneous group, even by histochemistry and electron microscopy a differentiated classification on a histogenetic basis is difficult because of overlaps in structural details. The aim of this study is checking by immunohistochemistry with antibodies to cytokeratins (KL 1), epithelial membrane antigen (EMA), S 100 protein (S 100), and glial fibrillary acidic protein (GFAP). Fourteen colloid cysts showed clear reaction differences of their epithelium in relation to neuroepithelium, which render feasible the verification of the earlier presumed bronchogenic origin of the former. Two other "ependymal cysts" could be classified as diverticulum respectively meningeal glioependymal cyst. A review is given about localization, clinical and neuroradiological aspects of these partly extreme rare lesions together with differential diagnosis.


[Laparoscopic hysterectomy assisted with robot. Report of first case in Mexico ].
Some 15 years ago since the DaVinci system is launched in the market and since then has been gaining ground in the field of surgery. There have been published case series and large casuisticals comparing the benefits from robotic surgery versus laparoscopic. In 2005 the Food & Drug Administration (FDA) approves its use for gynecological surgery. In Mexico, we have no experience in the use of this technology in this field of medicine. To describe the first laparoscopic hysterectomy case assisted with a robot (LHAR) intervened in Mexico, the results and review of the literature reported at the global level. this is a 47 year-old patient with clinical and ultrasonographic diagnosis of uterine fibroids of large items, who is scheduled for laparoscopic hysterectomy assisted with robot at Hospital Angeles del Pedregal in May of 2014. It examines the parameters of surgical time, transoperative bleeding, surgical complications, postoperative pain and hospital stay. It is also a review of the literature and compared the results obtained with what is reported in the literature world. The surgery had a duration of 2 hours 35 minutes. Blood loss was less than 50 mL. There were no complications and the patient had an EVA test of 2 at 24 hours after surgery. Hospital stay was 2 days. Laparoscopic hysterectomy assisted with a robot is a reliable procedure according to what is reported at the global level, offering benefits to both the surgeon and the patient.


Enzymatic generation of the amino terminus of the beta-amyloid peptide.
The major pathological change in Alzheimer's disease is the deposition of 39-42-amino acid beta-amyloid peptide (BAP) in the brain. Since BAP begins at the aspartate residue (Asp1, or codon 672 of the amyloid precursor protein (APP)770 transcript), the ability of several proteases to cleave the peptide bond methionine-Asp1 (M/D) was evaluated by using peptides and recombinant APP molecules as substrates. Cathepsin G and chymotrypsin cleave the synthetic peptide HSEVKMDAEF at M/D under acidic conditions, whereas cleavage at lysine-methionine (K/M) predominates when the pH is alkaline. Trypsin and cathepsins B, D, and L are unable to cleave the synthetic peptide at M/D. Peptide SEVNLDAEF, representing the mutation found in early onset Alzheimer's disease families from Sweden, is cleaved by cathepsin G and chymotrypsin at leucine-aspartate (L/D). Incubation of cathepsin G with soluble protease nexin-2 obtained from recombinant APP (APP-REP) derivatives resulted in proteolytic cleavage at or near the amino terminus of BAP. Cathepsin G-mediated cleavage was also observed in the domain representing the amino terminus of BAP when mature plasma membrane-associated APP-REP molecules were used as substrates. Our results strongly suggest the involvement of a chymotrypsin-like serine protease in the generation of the amino terminus of BAP beginning at Asp1.


Bilateral Diffuse Uveal Melanocytic Proliferation in a Patient with Recurrent Frontal Lobe Meningioma.
Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a paraneoplastic disorder that may be seen in patients with a known malignancy but more commonly is seen in those without any history of cancer. It leads to multiple uveal tumors with exudative retinal detachment along with thickening of the choroid and generally carries a poor prognosis. Its etio-pathogenesis is poorly understood but is said to involve factors secreted by the systemic malignancy that lead to proliferation of melanocytes in the uvea. We report the presentation and management of a female with history of treated frontal lobe meningioma who presented with neovascular glaucoma along with B-DUMP and was found to have recurrence of the meningioma on neuro-imaging. Central nervous system meningiomas can cause B-DUMP and management of the malignancy may lead to partial resolution of posterior segment manifestations of B-DUMP.


Rejection of grafts with no H-2 disparity in TAP1 mutant mice: CD4 T cells are important effector cells and self H-2b class I molecules are target.
Our previous results showed that TAP1 mutant mice rejected heart and skin grafts from donors with no H-2 disparity that express normal density of MHC class I molecules at the cell surface. During rejection, CD4 cells were predominant and essentially, no CD8 cells were found infiltrating the grafts. We hypothesized that TAP1 mutant mice, which developed and matured in an MHC class I-deficient environment, may have selected a repertoire of T cells with distinct reactivity to self class I molecules. The rejection of grafts with no H-2 disparity could be mediated by CD4+ T cells reactive to wild type H-2b class I molecules, or derived peptides, in the context of self-APC. Accordingly, we observed that transplanted TAP1 mutant mice presented a significant amplification of the proliferative T cell response to H-2Kb peptides, indicating that the stimulus with the graft was sufficient to induce peripheral expansion of these T cell repertoires. Therefore, the response to H-2Kb molecules could be a relevant pathway of activating T cells and triggering rejection of grafts expressing normal levels of these class I molecules. To test our hypothesis, we investigate the effect of pre-transplantation H-2Kb peptide-immunization on TAP1 mutant, which were then transplanted with C57BL/6 skin grafts (H-2b). Mice were immunized with a pool of five peptides derived from the polymorphic region of Kb alpha chain, before tail skin grafting. To study the role of CD4+ T cells in the rejection of C57BL/6 skin grafts, mice were in vivo depleted with an anti-CD4 monoclonal antibody GK1.5, and transplant evolution was observed. Sensitization of TAP1 mutant mice with H-2Kb peptides accelerated the rejection of skin grafts. Immunized mice rejected grafts with a MST of 13 days, compared to 16 days for the non-immunized mice (P=0.0089). The significant acceleration of graft rejection, induced by immunization with H-2Kb peptides, indicates that these peptides are capable of mobilizing effector T-cells that participate in rejection. These results support our hypothesis that class I molecules may be a target in the rejection of grafts with no MHC disparity. Depletion of CD4 T-cells resulted in a significant delay in rejection compared with the untreated control group. The MST of skin grafts in the controls was 16 days, whereas CD4-depleted recipients rejected skin grafts with a MST of 41 days (P=0.025). Moreover, some animals did not show macroscopic signs of rejection up to > 100 days posttransplantation. The contribution of CD4+ T cells to skin graft rejection, in our model, may reflect the occurrence of the presentation of H-2b peptides during graft rejection, in the context of self-APC. In conclusion, our results demonstrate an important role for H-2b molecules and CD4 T cells in the rejection of C57BL/6 grafts by TAP1 mutant mice. The low expression of MHC-I molecules on TAP1-/- mice may be determinant in the selection of a T cell repertoire strongly reactive to self MHC class I molecules which probably escapes the control of peripheral regulatory mechanisms.


The effect of maximum bite force, implant number, and attachment type on marginal bone loss around implants supporting mandibular overdentures: a retrospective study.
There remains controversy regarding the clinical reasons for late-implant bone loss, which is a critical factor in the long-term success of implant-supported overdentures. Assessment of the effect of such factors as attachment type, number of implants, gender, age, and maximum bite force (MBF) on marginal bone loss (MBL) around implants supporting mandibular overdentures. Sixty-two edentulous patients rehabilitated with two-, three-, or four-implant-supported mandibular overdentures at a university clinic between January 2006 and January 2007 and having a digital panoramic radiograph at the time of loading, were included in this study. All patients received digital panoramic radiographs, and MBL was measured by subtracting bone levels from the first radiograph. MBF was measured using a bite force transducer. The amount of bone loss 48 months after loading was found to be unrelated to gender, age, implant number, attachment type, and splinting (p = .741, p = .953, p = .640, p = .763, p = .370, respectively). A significant correlation was observed between the MBF and the MBL of distal implants on the right side (p < .01, 79.9%) and the MBF and the MBL of distal implants on the left side (p = .011, 34.6%). MBL around implants supporting mandibular overdentures seems not to be affected by number of implants, attachment type, age, or gender; however, MBL is affected by MBF.


The role of Src in solid and hematologic malignancies: development of new-generation Src inhibitors.
c-Src was the first protooncogene described and was among the first molecules in which tyrosine kinase activity was documented. c-Src has been defined as a common modular structure that participates in much of the crosstalk between the cytoplasmic protein tyrosine kinases and tyrosine kinase receptors. Understanding the structure and function of this important class of protein kinases and elucidating the molecular signaling events mediated by c-Src are important not only for identifying the critical pathways but also for designing new strategies to block or inhibit the action of these kinases. Despite the large amount of information available on c-Src, its precise functions in cancer remain to be elucidated. Recently, there has been renewed interest in c-Src as a molecular target for cancer therapy, and multiple c-Src inhibitors are entering clinical trials. In this review, the authors describe the function and expression of c-Src in human malignancies and the novel c-Src inhibitors and their potential applications for cancer treatment.


A unique tautomer of 1-n-hexyl-3-phenyl-1H-pyrazol-5-ol.
In the title compound, C15H20N2O, the bond distances and angles are consistent with the presence of the hydroxy tautomer. This tautomer was unambiguously determined by the clear presence of a H atom bonded to oxygen, as well as the total absence of any residual electron density around the N atom in the heterocycle, thus precluding any possibility of desmotropism.


An in vitro comparison of pH changes in root dentine following canal dressing with calcium hydroxide points and a conventional calcium hydroxide paste.
This study aimed to measure and compare pH changes at apical and cervical sites on the external root surface of extracted teeth dressed with calcium hydroxide in two different formulations. Root canals of 45 single-rooted extracted human teeth were accessed and shaped using a step-down technique with rotary instrumentation. Standard cavities were prepared on the external root surface at specific apical and cervical sites. The teeth were randomly allocated to three groups. Teeth in group A were dressed with calcium hydroxide points, those in group B were dressed with an aqueous calcium hydroxide paste and teeth in group C were left unfilled. Following storage in humid conditions, the pH of the dentine at apical and cervical sites was measured at baseline and then at 24 h, 72 h, 1 week, 10 days, 2 weeks and 3 weeks. The pH of the root dentine at both apical and cervical sites was significantly greater (P < 0.001) in teeth dressed with aqueous calcium hydroxide paste compared with those dressed with calcium hydroxide points, when averaged out across all time periods. For all groups, there was a significant difference between the mean apical and cervical pH values for each tooth with lower values for the apical sites (P < 0.001). The results of this study indicate that an aqueous calcium hydroxide paste was more effective than calcium hydroxide points at raising the pH on the external root surface of extracted teeth.


Thermal Modelling Analysis of Spiral Wound Supercapacitor under Constant-Current Cycling.
A three-dimensional modelling approach is used to study the effects of operating and ambient conditions on the thermal behaviour of the spiral wound supercapacitor. The transient temperature distribution during cycling is obtained by using the finite element method with an implicit predictor-multicorrector algorithm. At the constant current of 2A, the results show that the maximum temperature appears in core area. After 5 cycles, the maximum temperature is 34.5°C, while in steady state, it's up to 42.5°C. This paper further studies the relationship between the maximum temperature and charge-discharge current. The maximum temperature will be more than 60°C after 5 cycles at the current of 4A, and cooling measurements should be taken at that time. It can provide thoughts on inner temperature field distribution and structure design of the spiral wound supercapacitor in working process.


[The reward impact on the performance of verbal creative tasks: behavioral and EEG effects].
The aim of this study was to compare the effects of stimulating originality verbal instruction (IN1) and monetary reward (IN2) on originality of solutions of a verbal creative task and EEG-correlates of activity, determined on the basis of biopotentials power mapping in the frequency range 4-30 Hz. Right-handed students (10 men and 10 women) took part in experiment. An increase of solutions originality under the influence of monetary reward was revealed. At the promise of monetary reward in comparison with IN1, there was a global increase of the task-related theta2 power. Common to the teta1, 2 and alpha2 bands was increase in hemispheric asymmetry of these rhythms power with higher values in the right hemisphere of the brain. These changes have been observed already in the background EEG after IN2 and testify that generalized changes in hemispheric asymmetry provide the preparatory state after the promise of monetary reward. Regional brain activity changes were associated with beta2 rhythm. Under IN2 in comparison with IN1 the task-related power decreased in all posterior electrode sites except for frontotemporal. Reward-related EEG changes were more typical for men. In men only, promised monetary reward increased theta2 asymmetry and task-induced alpha power. Our results suggest that promise of monetary reward for creative thinking can increase verbal creativity. Gender differences in the reward-related EEG power changes show that men and women differ in neurophysiologic mechanisms that underlie increase of creativity.


Effects of chronic endothelin ET(A) receptor blockade on blood pressure and vascular formation of cyclic guanosine-3',5'-monophosphate in spontaneously hypertensive rats.
Endothelin (ET) mediates vasoconstriction in intact arterial blood vessels with functional endothelium via stimulation of ET(A) receptors, while ET(B) receptor stimulation leads to vasodilation via nitric oxide (NO) release and formation of cyclic guanosine-3',5'-monophosphate (cGMP). In spontaneously hypertensive rats (SHR) the cGMP-forming NO-receptor guanylyl cyclase (sGC) is downregulated. It is unclear whether ET contributes to the hypertensive phenotype of SHR, and whether this involves the disturbed cGMP signaling. The selective ETA receptor antagonist darusentan (CAS 171714-84-4), given orally via drinking water (10 mg kg(-1) d(-1)) for 12 weeks, significantly lowered systolic blood pressure of SHR as determined by radiotelemetry. Neither impaired endothelium-dependent relaxation to acetylcholine was restored nor sGC expression and activity affected when compared to control SHR. While these findings show a role for ETA receptors in blood pressure regulation in genetically elevated blood pressure, downregulation of sGC expression and cGMP-mediated vasorelaxant response in SHR were shown to be independent of ETA receptors. The findings suggest distinct mechanisms of gene expression affecting ET and cGMP mediated vasomotor functions.


Surgery and current management for cancer of the esophagus and cardia.
The current status of carcinoma of the esophagus is reviewed, with specific discussions on current problems. These are difficulties in staging the disease, confusion in the classification, surgery vs. radiation therapy, palliative vs. curative resection, transthoracic vs. transhiatal resection for palliation, and stomach vs. colon as an esophageal substitute after resection. The importance of dysphagia as the presenting complaint is stressed, and the etiologic factors for squamous and adenocarcinoma are reviewed, with a focus on Barrett's esophagus. In management, an emphasis is placed on intraoperative staging, the selection of patients for curative resection, the theory and use of en bloc resection, and the effect of tumor localization on the choice of surgical procedure. A description of the operative technique for cervical lesions, and transthoracic, transhiatal, and en bloc resection of thoracic lesions is given. The palliative benefit of bougienage, intubation, surgical bypass, radiotherapy, laser therapy, and electrical coagulation is summarized. The benefits of intubation are stressed. The recent advent of combination therapy, particularly with regard to chemotherapy and surgery, is discussed. Although such therapy is exciting in isolated patients, the results are not sufficiently predictable to be considered as standard therapy. More work needs to be done to identify those patients most apt to benefit from the variety of therapeutic modalities available.


PilP, a pilus biogenesis lipoprotein in Neisseria gonorrhoeae, affects expression of PilQ as a high-molecular-mass multimer.
Studies of gonococcal pilus biogenesis are fundamental to understanding organelle structure/function relationships and identifying new approaches to controlling disease. This area of research is also relevant to elucidating the basic mechanisms of outer membrane translocation of macromolecules, which requires components highly related to those involved in type IV pilus expression. Previous studies have shown that products of several ancillary pil genes are required for organelle biogenesis but of these only PilQ, a member of the GspD protein family, is a component of the outer membrane. DNA sequencing of the region upstream of pilQ revealed the presence of two open reading frames (ORFs) whose deduced polypeptides shared significant identities with proteins required for pilus expression in Pseudomonas aeruginosa and Pseudomonas syringae, the genes for which are arrayed upstream of a gene encoding a PilQ homologue. Gonococcal mutants bearing transposon insertions in these ORFs were non-piliated and failed to express pilus-associated phenotypes, and the corresponding genes were designated PilO and pilP. The piliation defects in the mutants could not be ascribed to polarity on distal pilQ expression as shown by direct measurement of PilQ antigen in those backgrounds and the use of a novel technique to create tandem duplications in the gonococcus (Gc) genome. As predicted by the presence of a consensus lipoprotein signal sequence, PilP expressed in both Escherichia coli and Gc could be labelled with [3H]-palmitic acid. PilP- as well as PilQ- mutants shed PilC, a protein which facilitates pilus assembly and is implicated in epithelial cell adherence, in a soluble form. Combined with the finding that levels of multimerized PiIQ were greatly reduced in PilP- mutants, the results suggest that PilP is required for PilQ function and that PilQ and PilC may interact during the terminal stages of pilus biogenesis. The findings also support the hypothesis that the Gc PilQ multimer corresponds to a physiologically relevant form of the protein required for pilus biogenesis.


Response to methadone maintenance treatment of opiate dependent patients with and without significant pain.
Both clinicians and researchers have expressed doubt that opiate dependent patients with significant pain can be effectively treated in methadone maintenance treatment (MMT) programs; however, little research exists on this topic. Patients who report significant pain in the month preceding entry to MMT present with a distinct and more severe pattern of polysubstance use, medical and psychosocial problems than do those without pain. The present study investigated the 1-year treatment outcomes of MMT patients with opiate dependence and pain. Analyses were based on a national sample of 200 patients presenting in MMT programs for treatment of opiate dependence. Substance use and related problems were measured at treatment entry and 12 months later. Patients reported pain severity over the month preceding treatment entry. Compared to patients without significant pain, patients who reported significant pain at baseline (n = 103) showed similar substance-related functioning, but poorer psychosocial functioning at 1 year. Patients with and without significant pain experience comparable reductions in substance use when provided with standard care in MMT programs. However, additional medical and/or mental health treatment is needed for their pain and other problems.


Accuracy Improvement of Braking Force via Deceleration Feedback Functions Applied to Braking Systems.
Currently, braking control systems used in regional railways are open-loop systems, such as metro and tramways. Given that the performance of braking can be influenced by issues such as wheel sliding or the properties of the friction components present in brake systems, our study puts forward a novel closed-loop mechanism to autonomously stabilize braking performance. It is able to keep train deceleration close to the target values required by the braking control unit (BCU), especially in terms of the electrical-pneumatic braking transform process. This method fully considers the friction efficiency characteristics of brake pads and encompasses running tests using rolling stock. The test results show that the technique is able to stabilize the actual deceleration at a closer rate to the target deceleration than before and avoid wheel sliding protection (WSP) action, especially during low-speed periods.


Effectiveness of deslorelin acetate subcutaneous implantation in a domestic queen with after-spaying urinary incontinence.
A 2-year-old female ovariectomised Norwegian Forest cat with a history of post-spaying urinary incontinence was diagnosed with acquired urinary sphincter mechanism incompetence (USMI) after complete clinical and laboratory examination. Although there is no literature regarding the treatment of post-spaying USMI in cats, deslorelin acetate is successful in the treatment of post-spaying USMI in dogs. Deslorelin acetate implants have been shown previously to be effective for contraception and oestrus suppression in queens, and suppression of reproductive function in tomcats. Therefore, deslorelin acetate implant treatment was chosen for treatment of post-spaying USMI in this queen. Follow-up examinations were performed on days 8, 15 and 30 after deslorelin implant insertion. Urinary continence was restored about 25 days after implantation and maintained for at least 15 months, without treatment-related negative effects. In the present case report, the post-spaying urinary incontinence related to the acquired USMI was successfully treated with a deslorelin acetate implant. In addition, safe implantation was easy in cats and the single injection resulted in long-lasting efficacy. Further studies are needed to confirm the usefulness of deslorelin acetate treatment for post-spaying USMI in queens and to better delineate the duration of efficacy.


Impact of savings groups on the lives of the poor.
Savings-led microfinance programs operate in poor rural communities in developing countries to establish groups that save and then lend out the accumulated savings to each other. Nonprofit organizations train villagers to create and lead these groups. In a clustered randomized evaluation spanning three African countries (Ghana, Malawi, and Uganda), we find that the promotion of these community-based microfinance groups leads to an improvement in household business outcomes and women's empowerment. However, we do not find evidence of impacts on average consumption or other livelihoods.


Aptamer-linked biosensor for thrombin based on AuNPs/thionine-graphene nanocomposite.
A novel protocol of electrochemical thrombin aptasensor based on a goldnanoparticles/thionine-graphene (AuNPs/Th-G) nanocomposite modified glassy carbon electrode was presented. Graphene was non-covalently functionalized by thionine viaπ-stacking interaction, and then AuNPs were electrodeposited onto the Th-G surface. The morphology and conductivity of the AuNPs/Th-G nanocomposite were characterized by scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The ethanethiol-substituted oligonucleotide probe was immobilized onto the surface of the AuNPs/Th-G nanocomposite to prepare an electrochemical biosensing platform. The aptamer-thrombin reaction was monitored by differential pulse voltammetry. Under optimum conditions, the proposed biosensor exhibits high sensitivity and a low detection limit for thrombin determination. The thrombin could be quantified in a wide range of 0.5 to 40 nM and with a low detection limit of 0.093 nM (S/N = 3).


In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014.
The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, ≥1 μg/ml; n = 3,428) and 9,371 isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-β-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points, Wageningen, the Netherlands) and published multiplex PCR assays. Testing identified 1,493 isolates that harbored a carbapenemase gene (1,485 ertapenem-nonsusceptible isolates and 8 ertapenem-susceptible ESBL-positive isolates) and accounted for 1.4% (1,493/103,960) of all isolates of Enterobacteriaceae The most frequently identified carbapenemase genes were the KPC (n = 794), OXA-48-like (n = 300), and NDM (n = 290) genes. Carbapenemase genes were most frequently identified in Klebsiella pneumoniae (n = 1,127), Escherichia coli (n = 149), and Enterobacter cloacae (n = 110). Among the carbapenemase-positive isolates, 66.7% (2/3), 37.0% (111/300), 20.0% (8/40), 3.3% (3/92), 2.3% (18/794), and 0% (0/290) of the isolates with genes for GES, OXA-48-like, IMP, VIM, KPC, and NDM, respectively, were susceptible to imipenem (MIC, ≤1 μg/ml). Isolates that tested as susceptible to imipenem were not uncommon among carbapenemase-positive isolates (9.4%, 141/1,493) and most frequently carried OXA-48-like enzymes (78.7%; 111/141); however, overall, these isolates remained rare (0.1%, 141/103,960). The practice of screening clinical isolates of Enterobacteriaceae that test as susceptible to carbapenems in vitro for the presence of carbapenemase genes remains controversial and requires further study.


13C-labeling reveals non-conventional pathways providing carbon for hydroxy fatty acid synthesis in Physaria fendleri.
Physaria fendleri is a Brassicaceae that produces hydroxy fatty acids in its embryos; a type of oil that is very valuable and widely used in the industry of cosmetics, lubricants, biofuels, etc. Free of toxins and rich in hydroxy fatty acids, Physaria is a promising alternative to imported castor oil and is on the verge of being commercialized. This study aims to identify important biochemical step(s) for oil synthesis in Physaria, which may serve as target(s) for future crop improvement. To advance towards this goal, the endosperm composition was analyzed by LC-MS/MS to develop and validate culture conditions that mimic the development of the embryos in planta. Using developing Physaria embryos in culture and 13C-labeling, our studies revealed that: i) Physaria embryos metabolize carbon into biomass with an efficiency significantly lower than other photosynthetic embryos; ii) the plastidic malic enzyme provides 42% of the pyruvate used for de novo fatty acid synthesis, which is the highest measured so far in developing "green" oilseed embryos; and iii) Physaria uses non-conventional pathways to channel carbon into oil, namely the RuBisCO shunt which fixes CO2 released in the plastid, and the reversibility of the isocitrate dehydrogenase which provides additional carbon for fatty acid elongation.


Exploration of brushing behavior among university students in Iran: a qualitative research.
Background Currently, it is estimated that 40% of the Iranian population is less than 20 years old, and in the academic year of 2011-2012 about 4 million students of that age were educated. The general assessment of the outcomes of oral health programs and investigating determinants is substantial for developing future plans of oral health. This study was done with the aim of exploring brushing behavior among university students of Iran to specify and understand the important determinants of oral health behavior. Methods A qualitative research method was used. This study was conducted between August and November 2016 in Shahid Beheshti University. Maximum variation sampling was used among university attendees and 44 students with more than 2 years of study duration were selected to be included in the research. Semi-structured interviews were employed for data gathering. All of the recorded interviews and notes were accurately evaluated and data analysis was performed based on the content analysis. Results As a result of the interview analysis 16 main categories emerged: Religious Beliefs, Perceived Benefits, Perceived Barriers, Habitation, Salience of Behavior, Education, Subjective Norms, Peer Pressure, Observational Learning, Knowledge, Perceived Susceptibility, Perceived Severity, Outcome Expectation, Skills, Perceived Self-efficacy, and Perceived Behavioral Control. Codes of sub-theme and theme were identified in the study. Conclusion This present study provides additional evidence with respect to the religious beliefs and the impact of religious instructions in brushing among students. Salience of brushing behavior has been described as one of the structures in an integrated behavioral model. Despite earlier studies suggesting, that peer pressure only plays a role on children's brushing behavior, our study showed that peer pressure is effective on adults as well.


An EGR performance evaluation and decision-making approach based on grey theory and grey entropy analysis.
Exhaust gas recirculation (EGR) is one of the main methods of reducing NOX emissions and has been widely used in marine diesel engines. This paper proposes an optimized comprehensive assessment method based on multi-objective grey situation decision theory, grey relation theory and grey entropy analysis to evaluate the performance and optimize rate determination of EGR, which currently lack clear theoretical guidance. First, multi-objective grey situation decision theory is used to establish the initial decision-making model according to the main EGR parameters. The optimal compromise between diesel engine combustion and emission performance is transformed into a decision-making target weight problem. After establishing the initial model and considering the characteristics of EGR under different conditions, an optimized target weight algorithm based on grey relation theory and grey entropy analysis is applied to generate the comprehensive evaluation and decision-making model. Finally, the proposed method is successfully applied to a TBD234V12 turbocharged diesel engine, and the results clearly illustrate the feasibility of the proposed method for providing theoretical support and a reference for further EGR optimization.


CT-navigated real-time ultrasonography: evaluation of registration accuracy for clinical application.
Ultrasound examination is a valuable diagnostic tool in almost all medical disciplines. However, the results are highly dependent on the experience and performance of the individual examiner and the technical conditions of the examination. Since computed tomography (CT) is not affected by these factors, the combination of real-time ultrasound images and previously compiled CT scans with identical cross-sections displayed simultaneously during transcutaneous ultrasonography could be advantageous. To evaluate the practical applicability and reliability of CT-supported transcutaneous ultrasonography, we examined 10 patients with a Real-Time Virtual Sonography Unit using a previously compiled CT scan as a reference. The results were evaluated by 10 sonographers with different levels of experience. By using the 3-point registration method almost identical ultrasound and CT cross-sections were displayed throughout the examination. However, there was a constant lateral and height deviation of the CT image detected. The crucial point is the correct and reliable referencing of the real-time ultrasound. In conclusion, the CT-navigated ultrasound seems not yet complete for clinical applications. Although helpful for training purposes, it is not accurate enough yet to play a role in routine clinical diagnostic work up.


Age of First Exposure to Collision Sports Does Not Affect Patient Reported Outcomes in Women and Men Community Rugby Players.
This study aimed to determine the relationship between age of first exposure (AFE) to repetitive head impacts through contact/collision sports and patient-reported outcomes in community rugby players. We recruited community rugby players older than 18 yr with at least 1 yr of contact rugby participation to complete an online survey. Participants completed the Brief Symptom Inventory-18 (BSI-18), Short-Form Health Survey 12 (SF-12), and Satisfaction with Life Scale (SWLS) via Qualtrics. We used generalized linear models to examine the association between AFE (continuous) and patient-reported outcomes by sex, while controlling for cumulative years contact/collision sport history, age, and concussion history (yes/no). In addition, we used Mann-Whitney U tests to compare patient-reported outcomes between AFE <12 and AFE ≥12. A total of 1037 rugby players (31.6 ± 11.3 yr (range, 18-74 yr), 59.1% men) participated in this study. Whether analyzed continuously or dichotomously at age 12 yr, younger AFE was not associated with worse patient-reported outcomes for either men or women. Positive concussion history was a significant predictor of worse BSI-18 subscores, SF-12 subscores, and SWLS in women and worse BSI-18 subscores in men. Cumulative contact/collision sport history was a significant predictor of better BSI-18 Depression and SF-12 (Mental Component Summary) subscores in men only. In men and women, older age was a significant predictor of better BSI-18 Depression, Anxiety, and GSI subscores; better SWLS (in men only); and better SF-12 Mental Component Summary, but worse SF-12 (Physical Component Summary). Younger AFE to contact/collision sport is not associated with worse patient-reported outcomes in early adult rugby players. Concussion history was predictive of worse patient-reported outcomes.


Changes in bone mineral density, bone turnover markers, and vertebral fracture risk reduction with once weekly teriparatide.
We aimed to evaluate the surrogacy of bone mineral density and bone turnover markers for incident vertebral fracture using data from 237 patients treated with once weekly 56.5 μg teriparatide or placebo. This analysis was conducted using data from the Teriparatide Once-Weekly Efficacy Research trial, a randomized, double-blind, placebo-controlled trial for patients with severe osteoporosis in Japan. A total of 237 subjects (placebo group, n = 130; teriparatide group, n = 107) were assessed at baseline and at 72 weeks. Main outcome measures included estimation of the treatment effects of once weekly teriparatide on vertebral fracture risk reduction using percentage changes in lumbar bone mineral density and bone turnover markers. The percentage change in lumbar bone mineral density was 6.69% in the teriparatide group compared with 0.28% in the placebo group (p < 0.01). One incident vertebral fracture occurred in the teriparatide group compared with 16 in the placebo group. The unadjusted and adjusted hazard ratios of the teriparatide group compared with the placebo group were 0.07 (95% confidence interval: 0.01 to 0.56) and 0.64 (95% confidence interval: 0.06 to 6.36), respectively. The proportion of treatment effect explained by changes in lumbar bone mineral density was 83% (Freedman's method) and 66% (Chen's method). There were no notable changes in hazard ratios if we adjusted for bone turnover markers. Most of the vertebral fracture risk reduction with once weekly 56.5 μg teriparatide is explained by changes in lumbar bone mineral density rather than changes in bone turnover markers.


A control technology evaluation of state-of-the-art, perchloroethylene dry-cleaning machines.
NIOSH researchers evaluated the ability of fifth-generation dry-cleaning machines to control occupational exposure to perchloroethylene (PERC). Use of these machines is mandated in some countries; however, less than 1 percent of all U.S. shops have them. A study was conducted at a U.S. dry-cleaning shop where two fifth-generation machines were used. Both machines had a refrigerated condenser as a primary control and a carbon adsorber as a secondary control to recover PERC vapors during the dry cycle. These machines were designed to lower the PERC concentration in the cylinder at the end of the dry cycle to below 290 ppm. A single-beam infrared photometer continuously monitors the PERC concentration in the machine cylinder, and a door interlock prevents opening until the concentration is below 290 ppm. Personal breathing zone air samples were measured for the machine operator and presser. The operator had time-weighted average (TWA) PERC exposures that were less than 2 ppm. Highest exposures occurred during loading and unloading the machine and when performing routine machine maintenance. All presser samples were below the limit of detection. Real-time video exposure monitoring showed that the operator had peak exposures near 160 ppm during loading and unloading the machine (below the OSHA maximum of 300 ppm). This exposure (160 ppm) is an order of magnitude lower than exposures with more traditional machines that are widely used in the United States. The evaluated machines were very effective at reducing TWA PERC exposures as well as peak exposures that occur during machine loading and unloading. State-of-the-art dry-cleaning machines equipped with refrigerated condensers, carbon adsorbers, drum monitors, and door interlocks can provide substantially better protection than more traditional machines that are widely used in the United States.


[Cyclothymic obsessive-compulsive disorder. Clinical characteristics of a neglected and under-recognized entity].
Clinical research is largely focused on depressive comorbidity in obsessional compulsive disorder (OCD). However some recent publications have suggested that bipolar comorbidity occurs in authentic OCD and its presence has a differential impact on the clinical picture and course of OCD. Recent data from the collaborative survey conducted with AFTOC (French Association of patients suffering from OCD) have revealed a high rate of bipolar comorbidity in OCD: 30% for hypomania and 50% for cyclothymia. The present paper presents further comparative analyses between OCD with (n = 302) versus without cyclothymia (n = 272). The sub-group "Cyclothymic OCD" is characterized by a different clinical picture (higher frequency of aggressive, impulsive, religious and sexual obsessions, and compulsions of control, hoarding, repetition), episodic course, higher rate of major depressive episodes (with more intensity and recurrence) associated with higher rates of suicide attempts and psychiatric admissions, and less favorable response to anti-OCD treatments. These data suggested that cyclothymic OCD could represent a specific distinct variant form of OCD. More vigilance is needed toward this entity which is largely under-recognized in clinical practice.


Response of plasma glucose, fructose and insulin to dietary glucose and fructose in the lactating sow.
Twenty-two Hampshire-Yorkshire X Large White sows of second and third parity were allotted randomly to one of three dietary treatments. Five sows were fed 6.0 kg/day of a corn-soybean meal lactation diet (control diet). Twelve sows were fed the control diet in which 24% of the composition was supplied by corn syrup containing 72% fructose on a dry matter basis (fructose diet) and five sows were fed the control diet in which 24% of the composition was supplied by powdered dextrose (glucose diet). All diets were fed from days 1 through 21 of lactation. Blood was collected from all sows immediately prior to feeding and hourly for 6 hours postprandial via jugular vein cannulae following a single feeding on seven separate but nonconsecutive days during the 21-day period. Fructose was absorbed from the digestive tract of sows as evidenced by elevated (P less than 0.01) conventions of fructose in plasma. Sows fed the fructose diet also had higher (P less than 0.01) plasma glucose concentrations than did those fed the glucose and control diets. The concomitant elevated glucose concentration following ingestion of the fructose diet was not associated (P greater than 0.10) with increased insulin concentration. Fructose in plasma was associated with a slight but significant increase in insulin although the mean concentration of insulin in plasma was only one-third that measured in sows fed the glucose and control diets. These data suggest that fructose in vivo has a glucose-sparing effect presumably mediated through a physiological mechanism that lowers insulin concentration.


Folding and interaction of subunits at the antibody combining site.
The Fv fragment derived from mouse myeloma protein 315 possessing anti-dinitrophenyl (DNP) activity, is composed of two subunits, the peptide chain VL and VH. In 8 M urea there is a complete dissociation of VL and VH and an approximately twofold increase in the fluorescence emission of Fv with a characteristic red shift of 11 nm. Upon dilution of Fv from 8 M urea into neutral buffer full regain of activity was observed, concomitant with regain of native fluorescence spectrum. The decrease in fluorescence upon dilution from 8 M urea was used to follow the renaturation process of Fv. At relatively high protein concentration (2.5 x 10(-6) M) two steps were observed during renaturation: a fast one, which is completed in less than 30 s, and a slower step, which proceeds for approximately 20 min. The fast process represents the refolding and association of VL and VH to form an active FV, whereas the slow step is attributed to the formation of "incorrect" associates between VL and VH which slowly reshuffle to the thermodynamically stable active FV. Indeed, at low protein concentration (1.5 x 10(-8 M) only the fast step is observed and renaturation is completed in less than 30s. The presence of hapten does not affect the rate of renaturation of FV. Reoxidation of FV completely reduced in 8 M urea was also found to yield a fully active Fv. Since either VL or VH have only one intrachain disulfide bond, reoxidation was performed at high protein concentration (3 mg/ml) in 8 M urea followed by dilution into neutral buffer. This demonstrates that variable domains not only exist in immunoglobulin structure but can also fold correctly independent of the rest of the peptide chains.


Reliability of clinical tests in the assessment of patients with neck/shoulder problems-impact of history.
A clinical trial on patients receiving neck/shoulder physical examinations. To analyze reliability of clinical tests, prevalence of positive findings in the assessment of neck/shoulder problems in primary care patients, and the impact of history, including pain drawing, on these parameters. Reliability of clinical tests varies, perhaps partly because of the impact of history. To our knowledge, this has not been studied before. Two examiners independently assessed 100 patients with a set of 66 clinical tests divided into 9 categories. Half of the patients were examined with and the other half without knowledge of history. Reliability as expressed by percentage agreement, kappa coefficients, and prevalence of positive findings was calculated. Reliability of clinical tests was poor or fair in several categories and did not alter with history. Only a bimanual sensitivity test reached good kappa values. With known history, prevalence of positive findings increased. Bias was apparent in all test categories except sensitivity tests. Four out of five patients were diagnosed to have neurogenic dysfunction in the affected area. Our sensitivity test was the most reliable and also exempt from bias and should be studied further. Some common tests may not be reliable. History had no impact on reliability of our tests but increased the prevalence of positive findings. Neurogenic dysfunction seems very common in patients with neck and/or shoulder problems and should be screened for.


A transactional stress theory of global work demands: A challenge, hindrance, or both?
We integrate research on global work demands (Shaffer et al., 2012) with transactional stress theory to examine both the harmful and beneficial effects of three global work demands-international travel, cognitive flexibility, and nonwork disruption-for employees engaged in global work. We propose that global work demands have indirect, and conditional, effects on burnout and work-to-family conflict (WFC), as well as thriving and work-family enrichment, through employees' appraisals that their global work is both hindering and challenging, respectively. We tested the hypotheses with a matched sample of 229 global employees and their spouses. We found that cognitive flexibility demands are related to harmful and beneficial outcomes: It increases WFC through hindrance appraisals of the global work, but also increases thriving through challenge appraisals. In comparison, international travel demands have only beneficial outcomes, such that it positively related to employee thriving through challenge appraisals, but only among employees working in jobs that have fewer nonwork disruption demands. Finally, nonwork disruption demands had only harmful effects in that it positively related to burnout and WFC through hindrance appraisals. Exploratory analyses also revealed that nonwork disruption demands negatively related to employee thriving, through challenge appraisals, when employees experienced lower levels of cognitive flexibility demands. These findings contribute to our understanding of how employees may react to their global work demands and to the transactional theory of stress by providing a more nuanced understanding of when and why job demands contribute to appraisals that work is hindering and/or challenging. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


A 4-fJ/Spike Artificial Neuron in 65 nm CMOS Technology.
As Moore's law reaches its end, traditional computing technology based on the Von Neumann architecture is facing fundamental limits. Among them is poor energy efficiency. This situation motivates the investigation of different processing information paradigms, such as the use of spiking neural networks (SNNs), which also introduce cognitive characteristics. As applications at very high scale are addressed, the energy dissipation needs to be minimized. This effort starts from the neuron cell. In this context, this paper presents the design of an original artificial neuron, in standard 65 nm CMOS technology with optimized energy efficiency. The neuron circuit response is designed as an approximation of the Morris-Lecar theoretical model. In order to implement the non-linear gating variables, which control the ionic channel currents, transistors operating in deep subthreshold are employed. Two different circuit variants describing the neuron model equations have been developed. The first one features spike characteristics, which correlate well with a biological neuron model. The second one is a simplification of the first, designed to exhibit higher spiking frequencies, targeting large scale bio-inspired information processing applications. The most important feature of the fabricated circuits is the energy efficiency of a few femtojoules per spike, which improves prior state-of-the-art by two to three orders of magnitude. This performance is achieved by minimizing two key parameters: the supply voltage and the related membrane capacitance. Meanwhile, the obtained standby power at a resting output does not exceed tens of picowatts. The two variants were sized to 200 and 35 μm2 with the latter reaching a spiking output frequency of 26 kHz. This performance level could address various contexts, such as highly integrated neuro-processors for robotics, neuroscience or medical applications.