Stimulation of gluconeogenesis by palmitic acid in rat hepatocytes: evidence that this effect can be dissociated from the provision of reducing equivalents.
When hepatocytes isolated from fasted rats were incubated in medium containing 5 mmol/L pyruvate, addition of albumin-bound palmitate (0.5 mmol/L) increased fatty acid oxidation and the conversion of pyruvate to glucose. Similar stimulation of gluconeogenesis occurred when palmitate was added to hepatocytes in medium containing 5 mmol/L alanine. Addition of 0.5 mmol/L (+)-octanoylcarnitine, an inhibitor of fatty acid oxidation, prevented the increment in beta-oxidation, but not the increase in glucose formation from pyruvate or alanine, induced by palmitate. These studies and other data to be considered subsequently indicate that palmitate can stimulate hepatic gluconeogenesis from three-carbon precursors under conditions that preclude an increase in the formation of reducing equivalents by beta-oxidation.


Defining sexuality in later life: A systematic review.
To identify whether a consistent definition of sexuality is used across research articles to describe sexuality in later life for heterosexual men and women. A systematic review was conducted that examined how researchers define sexuality for heterosexual adults. Peer-reviewed journal articles on sexuality published between 1999 and 2018 were examined for the presence of sexuality definitions. Sexuality themes discussed in each article were recorded, and results were tabulated. Few articles explicitly provide a definition of 'sexuality' as it pertains to later life. Definitions from articles that defined sexuality explicitly were inconsistent across studies. Topics included in implicit and explicit definitions of sexuality were disparate across studies and included a diverse range of sexuality dimensions. Greater consistency is needed in how "sexuality" in later life is defined across studies and should be informed by data so that it accurately reflects the sexual experiences of older adults.


[Diagnostics of ocular mucous membrane pemphigoid].
The diagnosis of ocular mucous membrane pemphigoid (MMP) remains a challenge as the timing and choice of diagnostic methods have a decisive influence on its quality. A systematic approach is required that includes a comprehensive medical history, critical evaluation of the clinical findings and targeted laboratory testing. The diagnosis is complicated by the fact that some patients present purely clinically the symptoms of MMP without fulfilling the required immunohistochemical and laboratory criteria. Basically, the diagnosis of ocular MMP is based on three pillars: 1) medical history and clinical findings, 2) positive immunohistological (direct immunofluorescence) tissue sample and 3) specific serological autoantibodies. As the diagnosis of ocular MMP often implies prolonged systemic immunomodulatory treatment in predominantly older patients, the accurate diagnosis and approach are of critical relevance. The aim of this article is to present the recently updated diagnostic procedure.


Uterine vein prostaglandin levels in late pregnant dogs.
We studied the uterine venous plasma concentrations of prostaglandins E2, F2 alpha, 15 keto 13,14 dihydro E2 and 15 keto 13,14 dihydro F2 alpha in late pregnant dogs in order to evaluate the rates of production and metabolism of prostaglandin E2 and F2 alpha in pregnancy in vivo. We used a very specific and sensitive gas chromatography-mass spectrometry assay to measure these prostaglandins. The uterine venous concentrations of prostaglandin E2 and 15 keto 13,14 dihydro E2 were 1.35 +/- .27 ng/ml and 1.89 +/- .37 ng/ml, respectively; however, we could not find any prostaglandin F2 alpha and very little of its plasma metabolite in uterine venous plasma. Since uterine microsomes can generate prostaglandin F2 alpha and E2 from endoperoxides, prostaglandin F2 alpha production in vivo must be regulated through an enzymatic step after endoperoxide formation. Prostaglandin E2 is produced by pregnant canine uterus in quantities high enough to have a biological effect in late pregnancy; however, prostaglandin F2 alpha does not appear to play a role at this stage of pregnancy.


Impact of glucose polymer chain length on heat and physical stability of milk protein-carbohydrate nutritional beverages.
This study investigated the impact of glucose polymer chain length on heat and physical stability of milk protein isolate (MPI)-carbohydrate nutritional beverages containing 8.5% w/w total protein and 5% w/w carbohydrate. The maltodextrin and corn syrup solids glucose polymers used had dextrose equivalent (DE) values of 17 or 38, respectively. Increasing DE value of the glucose polymers resulted in a greater increase in brown colour development, ionic calcium, protein particle size, apparent viscosity and pseudoplastic rheological behaviour, and greater reduction in pH, hydration and heat stability on sterilisation at 120°C. Incorporation of glucose polymers with MPI retarded sedimentation of protein during accelerated physical stability testing, with maltodextrin DE17 causing a greater reduction in sedimentation velocity and compressibility of sediment formed than corn syrup solids DE38. The results demonstrate that chain length of the glucose polymer used strongly impacts heat and physical stability of MPI-carbohydrate nutritional beverages.


The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency.
To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ≥0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the ACADVL gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation. Retrospective analysis based on the C14:1/C2 ratio with a cutoff of ≥0.020 identified an additional five children with known ACADVL mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2-5 years). Increasing the cutoff to ≥0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ≥0.8) was 50%. This study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. However, as these patients were all asymptomatic at the time of diagnosis, this suggests that a more sensitive screening approach may also identify individuals who may never develop clinical disease. Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms.


Psychological Aspects of Pregnancy and Lactation in Patients with Breast Cancer.
Young breast cancer patients face numerous challenges during the cancer trajectory. As in the last decade, women tend to delay pregnancies to a later time in life, and clinicians are often faced with young breast cancer patients who want to start a family or complete it. Becoming a mother is a delicate developmental process in which the woman redefines and restructures her identity as she gets prepared for her new role and responsibilities. When there is a history of cancer or cancer diagnosis is communicated during the pregnancy, fears, worries, and concerns emerge and specific support may be necessary. Follow-ups during the post-partum period are also recommended as lactation issues should not be overlooked. In this chapter, we analyze the psychological aspects of cancer survivors and women with pregnancy-associated breast cancer, and the management of these issues.


Interactions of radiation and adriamycin, bleomycin, mitomycin C or cis-diamminedichloroplatinum II in intestinal crypt cells.
The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost constant enhancement of the radiation response, the dose effect factor (DEF) being 1.19. The effect of BLM was extremely dependent on the sequence and interval between drug administration and irradiation. The most pronounced effect was observed when BLM was given 2 h before irradiation (DEF = 2.40), at which interval the D0 surprisingly increased by a factor of 1.4. Administration of MM-C from 24 h before to 24 h after irradiation enhanced the radiation response. The effect peaked on administration 6 h before irradiation (DEF = 1.21) and diminished by application after irradiation. Cis-DDP enhanced the radiation response only when given before irradiation resulting in a DEF of 1.23 and a decreased D0.


Perception of Non-Vibrato Sung Tones: A Pilot Study.
Singers are often asked to sing with a non-vibrato production. The term non-vibrato is problematic in that it is not possible for a human to sing a tone without fundamental frequency variation. Whether a singer achieves a quality of tone that is perceived as non-vibrato is an aurally subjective matter. The specific aim of this study was to determine when a tone is perceived as non-vibrato by a population of singers, voice teachers, choir directors, and speech pathologists. Using voice samples that exhibit a variety of vibrato rates and extents, the investigators sought to determine (1) if there is a threshold for the perception of non-vibrato tone with regard to vibrato extent; (2) if vibrato rate, given similar vibrato extent, does affect the perceptual threshold of non-vibrato tone; and (3) if there are differences in the perceptual threshold of non-vibrato tone across the different professions of the research subjects. Survey. Participants responded to an online survey featuring 40 randomized samples of soprano voices singing [ɑ] with a variety of vibrato rates and extents. Some samples were repeated to test subject response reliability. Results indicate that a perceptual threshold exists with regard to vibrato extent. However, vibrato rate significantly affected where this extent threshold occurred for the participants. Vibrato extent and rate work together to affect perception of non-vibrato tone. Significant differences were not found across the different groups.


Epidemiological differences between adenocarcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA.
It has been suggested that gastric cardia adenocarcinoma (GCA) is a distinct entity from oesophageal adenocarcinoma (OA). We examined several epidemiological features of GCA and OA in the USA to elucidate differences/similarities between these malignancies. Using the database of Surveillance, Epidemiology, and End Results (SEER) program, we examined incidence rates for temporal changes, and ethnic and age distributions, and performed birth cohort analyses for cases with morphologically and histologically confirmed OA or GCA. The age adjusted incidence rates of OA rose progressively, reaching 1.8 per 100 000 (95% confidence interval 1.7-1.9) during 1987-1991 and 2.5 per 100 000 (2.3-2.6) during 1992-1996. In 1992-1996, Whites were affected five times more than Blacks, and men eight times more than women. A significant increase in incidence occurred among younger persons aged 45-65 years. Irrespective of age, OA was characterised by higher incidence rates among more recent birth cohorts: a 40% increase in incidence for each five year increase in the date of birth--a "birth cohort effect". On the other hand, the incidence rates of GCA reached their highest level of 3.3 per 100 000 (3.2-3.4) in 1987-1991 and subsequently declined during 1992-1996 to 3.1 per 100 000 (3.0-3.3). Whites were affected twice more than blacks and men five times more than women. Most patients with GCA were older than 60 years with no increase among younger persons and no birth cohort effect (p=0.99). Several significant epidemiological differences exist between OA and GCA. These differences suggest that these two malignancies are separate entities with different risk factors.


[Plasma separation in acute, intravenous phenytoin poisoning].
A two year old boy suffered an acute phenytoin intoxication following intravenous treatment of seizures. After two days in coma detoxification with plasma separation was started. The course of clinical symptoms and phenytoin elimination is described and the efficacy of the method in treating phenytoin intoxication is discussed.


Pregnancy complicating irradiation-induced constrictive pericarditis.
A case is reported of a 24-year-old primigravida who had severe effusive constrictive pericarditis secondary to mediastinal irradiation following chemotherapy for Hodgkin's disease. Pregnancy was threatened by serious maternal cardiovascular complications, and a non-viable fetus was born spontaneously and prematurely. Patient was completely asymptomatic before pregnancy.


HIV prevalence among transgender women in Northeast Brazil - Findings from two Respondent Driven Sampling studies.
The HIV epidemic still high among key-populations in Brazil, especially among transgender women (TGW). The aim of this study was to investigate the prevalence of HIV infection among TGW and to analyze factors associated with HIV seropositivity across two cross-sectional surveys conducted in Salvador, Bahia, one of the largest urban centers of Brazil. The studies were conducted between 2014 and 2016 and 2016-2017 and employed Respondent-Driven Sampling (RDS) sampling, comprising 127 and 161 TGW residents of Salvador, Bahia. The outcome was the positive rapid antigen testing for HIV infection. Odds ratios (OR) and 95% confidence intervals (95%CI) were obtained using binomial logistic regression. The HIV prevalence was 9.0% (95%CI: 4.2-18.2) and 24.3% (95%CI: 16.2-34.9). In the first study, factors associated with HIV prevalence were experiencing discrimination by the family (OR 8.22; 95%CI: 1.49-45.48) and by neighbors (OR 6.55; 95%CI: 1.12-38.14) as well as having syphilis (OR 6.56; 95%CI:1.11-38.65); in the subsequent study gender-based discrimination (OR 8.65; 95%CI:1.45-51.59) and having syphilis (OR 3.13; 95%CI: 1.45-51.59) were associated with testing positive for HIV. We found disproportionately high HIV prevalence among TGW, which underscores the context of vulnerability for this population. The data point to the urgency for intensification and expansion of access to HIV prevention and strategies to stop discrimination in health care and services for this population.


Technique for subcutaneous implantable cardioverter-defibrillator extraction.
There are no established methods for subcutaneous implantable cardioverter-defibrillator (S-ICD) extraction other than simple manual traction for devices with short dwell time. However, as more chronic indwelling S-ICDs need removal for various reasons, understanding the S-ICD lead design and methods for its removal are essential. A case of a chronic indwelling S-ICD extraction is described, and a technique utilizing a modified mechanical polypropylene sheath to safely remove the lead is outlined in detail.


Mental symptoms and quality of life in lipoprotein apheresis patients in comparison to hemodialysis patients, platelet donors and normal population.
Despite the fact that extracorporeal methods such as lipoprotein apheresis (LA) and hemodialysis (HD) are highly effective in improving the physical status of patients, these treatment options may possibly harm the psychological status and the health related quality of life (HRQL). The occurrences of anxiety, depression and the HRQL of 111 study participants treated with LA (n = 41), HD (n = 41) or undergoing plateletpheresis (PD) (n = 29) were compared to the normal population (NP), using standardized questionnaires (anxiety and depression: Hospital Anxiety and Depression Scale (HADS), heart-focused anxiety: Cardiac Anxiety Questionnaire (CAQ) and HRQL: Short-Form Health Survey (SF-12)). Additionally, the subjective mental and physical stress of study participants was evaluated. LA females had a significantly elevated HADS-A score compared to PD and NP. Additionally, there was a trend toward higher HADS-A scores in the LA group compared to the HD group in females. In HD males HADS-A and -D scores increased compared to PD and NP. The CAQ revealed a significant increase in the CAQ-Fear scale in LA compared to HD and PD participants. The CAQ-Avoidance score showed significantly increased scores in LA and HD patients compared to PD and NP. In the CAQ-Attention scale the LA patients also showed significantly increased scores compared to PD and NP. The increased psychological symptoms were associated with significantly lower levels of objective and subjective HRQL in LA and HD patients compared to PD and NP. LA and HD patients had similarly increased presence of psychological symptoms with concurrent decreased quality of life compared to PD and the normal population, which may affect the outcome of the LA patients. Therefore, early psychosomatic screening and probable psychosomatic treatment should be performed.


Tractor nail as impacted foreign body: rare case scenario.
A patient presented with a metallic nail impacted in the right orbital floor after being hit by a projectile. The nail was disimpacted and removed as guided by the radiograph image. Radiography proved helpful in forming a coherent scheme for case management.


Value of Multidetector-row Computed Tomography in Diagnosis of Portal Vein Invasion by Perihilar Cholangiocarcinoma.
Although knowledge of cancer invasion of the portal bifurcation is vitally important in planning an operation for perihilar cholangiocarcinoma, the diagnostic capability of multidetector-row computed tomography (MDCT) for this purpose has not been assessed. We evaluated how well MDCT could identify cancer invasion of the portal bifurcation by perihilar cholangiocarcinoma. Between April 2003 and June 2005, perihilar cholangiocarcinoma was resected in 87 patients, 83 of whom underwent MDCT within 1 month before the surgery. Three-dimensional volume-rendered (3DVR) and multiplanar reformation (MPR) images were examined for evidence of portal vein invasion. Agreement with intraoperative and pathologic findings was assessed. Portal bifurcation findings by 3DVR and MPR were classified into no portal vein stenosis, unilateral stenosis, or more extensive stenosis, and also into tumor contact with the bifurcation in no, one of two, or two projections. For macroscopic portal vein invasion, sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 81.5, 91.1, 81.5, 91.1, and 88.0% in 3D portography and 96.3, 92.6, 86.7, 98.1, and 94.0% in MPR, respectively. Findings by both 3DVR and MPR were significantly correlated with depth of cancer invasion (p < 0.001). MDCT is useful in assessing cancer invasion of the portal vein bifurcation by perihilar cholangiocarcinoma.


Tuning phononic and electronic contributions of thermoelectric in defected S-shape graphene nanoribbons.
Thermoelectrics as a way to use waste heat, is essential in electronic industries, but its low performance at operational temperatures makes it inappropriate in practical applications. Tailoring graphene can change its properties. In this work, we are interested in studying the transport properties of S-shape graphene structures with the single vacancy (SV) and double vacancy (DV) models. The structures are composed of a chiral part, which is an armchair graphene nanoribbon, and two zigzag graphene ribbons. We investigate the changes in the figure of merit by means of the Seebeck coefficient, electronic conductance, and electronic and phononic conductances with the vacancies in different device sizes. The transport properties of the system are studied by using the non-equilibrium Green's function method, so that the related Hamiltonians (dynamical matrices) are obtained from the tight-binding (force constant) model. The maximum figure of merit (ZT) obtains for the DVs in all lengths. Physical properties of such a system can be tuned by controlling various parameters such as the location and the type of the defects, and the device size. Our findings show that lengthening the structure can reduce phononic contribution, and single vacancies than double vacancies can better distinguish between electronic thermal conductance behavior and electronic conductance one. Namely, vacancy engineering can significantly increase thermoelectric performance. In the large devices, the SVs can increase the ZT up to 2.5 times.


Conformationally constrained inhibitors of caspase-1 (interleukin-1 beta converting enzyme) and of the human CED-3 homologue caspase-3 (CPP32, apopain).
A systematic study of interleukin-1 beta converting enzyme (ICE, caspase-1) and caspase-3 (CPP32, apopain) inhibitors incorporating a P2-P3 conformationally constrained dipeptide mimetic is reported. Depending on the nature of the P4 substituent, highly selective inhibitors of both Csp-1 or Csp-3 were obtained.


Luteal phase salivary progesterone concentrations in ovulation-induced cycles.
Serial paired plasma and salivary progesterone (P) levels were determined in 21 ovulation-induced cycles of 13 women and in 162 luteal saliva samples of 21 normal cycling women. Mean +/- standard error of the mean (SEM) salivary P levels in all ovulation-induced cycles were similar to normal cycles and were 294 +/- 31.5 to 499 +/- 75 pg/ml, whereas the corresponding plasma P levels were 24.9 +/- 5.0 to 51.4 +/- 16.6 ng/ml. Paired plasma and salivary P levels correlated significantly in women induced with clomiphene citrate (r = 0.82), follicle-stimulating hormone (r = 0.80), human menopausal gonadotropins (r = 0.78), and in those who became pregnant (r = 0.95). Luteal phase salivary P levels were 1.0% to 1.3% of the corresponding plasma levels in ovulation-induced cycles. These findings indicate that salivary P may be a useful and convenient alternative to plasma P for assessing ovulation.


[Treatment of vascularised serous pigment epithelium detachment in AMD - observations after changing the intravitreal agent due to lack of response].
Based on data from multicentric studies the treatment of exudative age-related macular degeneration (AMD) with VEGF inhibitors has recently become a more and more standard procedure. Nevertheless, the proper end point of the treatment and also the adequate interval between single injections have not been defined yet. In subtypes of AMD associated with pigment epithelium detachment. (PED) the natural course as well as laser coagulation treatment and photodynamic therapy (PDT) showed unsatisfactory results. The main cause of decreased visual acuity has proven to be recurrence of choroidal neovascularisation and ruptures of the pigment epithelium (RIP). This retrospective study presents the clinical results following a change of the injected VEGF inhibitor after ineffective initial therapy. 15 patients with serous PED, 7 patients with PED associated with retinal angiomatous proliferation (RAP) exhibited insufficient stabilisation after initial treatment with pegaptanib (Macugen). Therefore we continued treatment with ranibizumab (Lucentis). The mean age was 74.67 years. Best corrected visual acuity was evaluated with logMAR. Additional morphological parameters were fovea full thickness (OCT), measurement of the height of pigment epithelium detachment and finally fluorescein and indocyaningreen angiography. In cases of functional and morphological deterioration, we changed the treatment from 1.25 mg pegaptanib (Macugen) to 0.5 mg ranbizumab (Lucentis). During the mean follow-up of 46.5 weeks (95 % CI 35.9 - 57.1) no RIP occurred. After changing the drug, visual acuity showed a stabilisation or improvement in 11 cases. Also the height of PED decreased after beginning with ranbizumab. Regarding the therapeutic outcome, no difference between eyes with serous PED caused by occult CNV or RAP could be observed. Treatment using VEGF inhibitors in patients suffering from AMD with exudative serious PED has proven to be effective regarding both the morphological damage and functional injuries. In cases of therapeutic failure after pegaptanib functional and/or morphological stabilisation of the course of this disease can be achieved by changing to ranbizumab. Nevertheless, prospective clinical studies with a larger number of patients are necessary for confirmation of these findings.


Peroxisome proliferator-activated receptor γ attenuates serotonin-induced pulmonary artery smooth muscle cell proliferation and apoptosis inhibition involving ERK1/2 pathway.
Serotonin (5-HT) has been shown to be involved in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) by inducing pulmonary artery smooth muscle cells (PASMCs) proliferation and inhibiting PASMC apoptosis. Peroxisome proliferator-activated receptor γ (PPARγ) plays a crucial role in regulating proliferation and apoptosis of many cell types. Moreover, recently, loss of PPARγ has also been reported to be associated with the development of PAH. The present study is aimed to assess whether PPARγ is involved in 5-HT induced PASMC proliferation and apoptosis inhibition and the possible mechanism. We found that 5-HT could induce PASMC proliferation and inhibit PASMC apoptosis in a dose-dependent manner. Furthermore, we found that 5-HT negatively regulated PPARγ expression and gene promoter activity in PASMCs and 5-HT induced PASMC proliferation and apoptosis resistance could be abolished by PPARγ agonists and enhanced by PPARγ inhibitor. In addition, we found that extracellular signal-regulated kinase (ERK) signaling pathway mediated the 5-HT-induced inhibition of PPARγ expression. Our results might provide novel insights into the mechanisms for the pro-remodeling action of 5-HT in pulmonary vasculature.


Direct measurement of androgen receptors in cultured Sertoli cells.
Cytoplasmic and nuclear forms of macromolecules with the properties of androgen receptors have been demonstrated by direct labeling techniques in cultured Sertoli cells. The cytoplasmic form was excluded from Sephadex G-200 and could be distinguished from androgen binding protein (ABP) on the basis of size, heat stability, relative electrophoretic mobility, and binding complex dissociation rate. When cultured Sertoli cells were incubated with 3H-testosterone, a time- and temperature-dependent accumulation of label into the nuclear fraction was observed, 46% of which crystallized as authentic testosterone. Specific binding was saturable with an apparent association constant of 0.4nM-1. Approximately 30% of the nuclear bound hormone was extracted within 1 h by 0.4M KCl and 34% of this was associated with macromolecular species as measured by gel filtration. Unlabeled androgens and to some degree progestogens competed with 3H-testosterone for binding sites. These data constitute direct evidence that Sertoli cells contain androgen receptors.


The teaching of neurosurgery in UK medical schools: a message from British medical students.
A great variability exists in the clinical exposure of neurosurgery across all academic years in UK medical schools, although the effects of this on knowledge level and confidence in referring cases appropriately to specialists have not been reported. A cross-sectional study was carried out involving students in years 1-5 across nine British medical schools. An electronic questionnaire was sent out which consisted of questions concerning the teaching of the subject; and questions assessing the knowledge of basic neurosurgery through mini clinical scenarios testing which specialty should receive a referral. Of 417 participants, 60 were excluded due to incomplete participation. Senior years outperformed students in junior years for correctly answered questions on five neurosurgical scenarios (mean score: years 1-3 (184/357) = 3.33/5, years 4-5 (173/357) = 3.79/5, p < 0.05). Participants in years 1-5 with prior clinical exposure in neurosurgery scored higher than participants who had no exposure (mean score: exposed (247/357) = 4.21/5, not-exposed (110/357) = 3 · 50/5, p < 0.05). Sixty-one percent prefer receiving neurosurgical teaching via increased exposure to operations. Students in years 4-5 with exposure in both classroom and operating theatre scored higher than students with classroom-only experience (mean classroom (69/131) = 3.62/5, mean classroom and operating theatre (62/131) = 4.21/5, p < 0.05); 33.3 % of final-year students reported difficulty in identifying patients that require neurosurgical referral. Students with exposure to an operating theatre outperformed those students exposed to just classroom teaching. Students indicated an increased preference for teaching through the operating theatre scene. One in three final-year medical students had difficulty identifying the need for a neurosurgical referral.If neurosurgical teaching were further enhanced at medical school, it could lead to increased confidence and efficiency in junior-year doctors when facing the neurosurgical referral process. Increased exposure to clinical neurosurgery may significantly improve the ability of future doctors to tackle neurosurgical scenarios.


Genetic transformation of the phytopathogenic bacteria, Erwinia chrysanthemi.
Erwinia chrysanthemi is an enterobacterium whose phytopathogenicity is due to its pectinolytic and cellulolytic activities. The CaCl2 mediated transformation procedure was successfully applied to two E. chrysanthemi wild type strains. The highest efficiency of transformation of E. chrysanthemi with pBR322 was found using 0.1 M CaCl2, 0.1 M MgCl2 treated cells and a heat pulse at 30 degrees C for 6 min. This yielded about 600 transformants per microgram of pBR322 DNA and 2.3 X 10(-6) per viable cell. Plasmid stability after twenty generations was lower than in E. coli: only 40-60% of the cells retained the plasmid in the absence of selective pressure. Based on this result, cloning in E. chrysanthemi with pBR322 vectors should therefore be possible, making it a potential host for cloning any gene for biomedical or industrial purposes.


Cell-free fetal DNA and maternal serum analytes for monitoring embryonic and fetal status.
Biomarkers can be employed for screening for fetal genetic disorders, identifying individuals at sufficiently high risk for a confirmatory invasive procedure. In this article we discuss prenatal genetic aneuploidy screening. Maternal serum analytes and ultrasound have long been routinely offered, providing detection rates of 80% to 93% for trisomy 21; however, an invasive procedure (false-positive) must be performed in 5% of pregnancies screened. Recovering fetal cells from maternal blood initially proved inconsistent, but new methods recovering trophoblasts offer promise for detecting disorders using a single fetal cell, analogous to preimplantation genetic diagnosis. Current emphasis is focused predominantly on cell-free fetal DNA, which accounts for 5% to 10% of total cell-free DNA in maternal blood. Analysis of maternal blood results in detection rates of over 99% for fetal trisomy 21, and also very high rates for trisomy 18 and sex chromosomal abnormalities. Such detection rates are substantively higher than with maternal serum analytes, and are accompanied by a much lower (<1%) false-positive rate.


Development and application of a laboratory flux measurement system (LFMS) for the investigation of the kinetics of mercury emissions from soils.
Recent measurements at different locations suggest that the emission of mercury from soils may play a more pronounced role in the global mercury cycle as suggested by global emission inventories and global mercury cycling models. For up scaling and modelling of mercury emissions from soils a comprehensive assessment of the processes controlling the emission of mercury from soils is imperative. We have developed a laboratory flux measurement system (LFMS) to study the effect of major environmental variables on the emission of mercury under controlled conditions. We have investigated the effects of turbulent mixing, soil temperature and solar radiation on the emission of mercury from soils. The emission of mercury from soils is constant over time under constant experimental conditions. The response of the mercury emission flux to variations of the atmospheric transfer parameters such as turbulence requires a rapid adjustment of the equilibrium that controls the Hg(o) concentration in the soil air. It has been shown that the light-induced flux is independent of the soil temperature and shows a strong spectral response to UV-B.


Anti-HCV antibody presence in hemodialyzed patients: assessment after one year regarding some preventive measures chosen.
The authors report on the presence of anti-HCV antibodies in a uremic chronic (UC) patient population after 6 months and 1 year with regard to certain selective preventive measures. The nonincreased number of HCV-positive subjects among the UC population could lead to the conclusion that the risk of environmental spreading of HCV is less than the risk of HBV diffusion.


Influence of Dorper lamb development from birth to 120 days of age on clinical and echocardiographic parameters.
The expansion of the sheep model in research represents an attractive and economically beneficial academic reason for investigations in sheep echocardiography. The present study aimed to evaluate the clinical and echocardiographic parameters in Dorper lambs during the developmental period. Emphasis was placed on the use of the species in translational research for the echocardiographic diagnosis of congenital heart diseases, which can contribute to improvements in interventionist techniques. Ten Dorper lambs were evaluated at the following time points: 24 h after birth and 7, 14, 21, 30, 60, 90 and 120 days of age. Clinical parameters were compiled, and echocardiogram records were obtained without sedation. Rectal temperature was lower on the first day compared to the others. From 21 days of life, there was a reduction in HR, with differences between time points. Mean and systolic blood pressure differed, with the highest values at 90 and 120 days of age. The thickness of the interventricular septum in diastole (IVSd) increased as age progressed, with the highest value at 120 days of age, and the same occurred for LVIDd (left ventricle internal diameter in diastole), LVFWd (left ventricular free wall thickness in diastole), IVSs (interventricular septum thickness in systole), LVIDs (left ventricle internal diameter in systole) and LVFWs (left ventricular free wall thickness in systole). There were differences in the size of the LA, Ao and LA/Ao ratio, which were greater at 90 days and 120 days of age. Echocardiographic changes accompany the development of lambs, where changes in echocardiographic parameters are evident with advancing age. The echocardiographic measurements in lambs obtained in the present study are similar to those in newborns.


Intramural pseudodiverticulosis of the esophagus.
Esophageal intramural pseudodiverticulosis (EIPD) is a rare condition seen in the elderly, with a male-to-female ratio of 3:2. Multiple small outpouchings occur in the submucosa of the esophageal wall, caused by dilation of the excretory ducts of the mucus glands. This disorder may be associated with gastroesophageal reflux, motility disorders, candidiasis, or other conditions. Inflammation, resulting in periductal fibrosis and compression of the duct orifices, may be a causative factor. Usually, EPID presents with progressive dysphagia related to esophageal stenosis or strictures in the great majority of patients. Radiologic examination is more sensitive than endoscopy in detecting these tiny saccular diverticula in the esophageal wall. They often are noted to disappear after esophageal dilation, but may persist asymptomatically in some patients. We report two cases of dysphagia associated with reflux and Candida infection in elderly patients. The diagnosis of EIPD was made, and both patients were treated successfully. A review of the available literature suggests that EIPD may be missed easily because of subtle endoscopic and radiologic changes, but that once diagnosed, conservative management leads to satisfactory control of the symptoms.


Sarcomatoid urothelial carcinoma of the ureter with heterologous elements of chondrosarcoma and osteosarcoma, and concurrent divergent squamous differentiation: A rare case report.
Primary sarcomatoid urothelial carcinoma of the ureter with heterologous elements is rare and carries a poor prognosis. Although there is some literature on primary bladder sarcomatoid urothelial carcinoma, ureteric involvement has been reported infrequently, and this case report describes this unusual histological finding with concurrent divergent squamous differentiation. Despite laparoscopic radical nephroureterectomy, our patient died within six months of diagnosis with local recurrence and metastatic spread. A more thorough understanding of this disease process and consideration of standardised guidelines for treatment are needed to improve patient outcomes.


Rising childhood income inequality and declining Americans' health.
Morbidity and mortality are on the rise among Baby Boomers and younger cohorts. This study investigates whether this unfavorable health trend across birth cohorts 1925-1999 is related to rising income inequality Americans face during childhood. We use two nationally representative datasets: National Health and Nutrition Examination Surveys (NHANES) 1988-2018 and Panel Studies of Income Dynamics (PSID) 1968-2013, and two health outcomes: biomarkers of physiological dysregulation, and a chronic disease index. Childhood income inequality is measured by the average of the Gini index at the national level each birth cohort is exposed to between birth and age 18, where the Gini index from 1925 to 2016 is computed based on Internal Revenue Service income data. By merging childhood income inequality to individual level data from NHANES or PSID based on birth cohort, we find childhood income inequality is positively associated with the risk of physiological dysregulation in adulthood for all gender and racial groups in the NHANES data. It is also significantly related to the risk of chronic disease in the PSID data. This association is robust to controls for individual level childhood health and family background, adulthood socioeconomic and marital status, and contemporary macro socioeconomic factors. More importantly, childhood income inequality exposure explains a substantial amount of variation in these two health outcomes across cohorts, a pattern not observed for other early life exposures that display negative temporal trends similar to those for childhood income inequality. This study provides important evidence that income inequality experienced during childhood may have a long-lasting negative consequence for adult health, which partially explains the adverse health trends experienced by Baby Boomers and younger cohorts in the United States.


Gas-liquid chromatographic determination of 1,3-dihydro-3-phenylspiro(isobenzofuran-1,4-piperidine), HP 505, in biological fluids using a nitrogen-specific detector.
A gas chromatographic method for the determination of 1,3-dihydro-3-phenylspiro[isobenzo-1,4-piperidine], HP 505, in plasma red blood cells and urine has been developed. HP 505 and internal standard are extracted from basified fluid with hexane and then back extracted into acetic acid. After re-extraction into hexane, HP 505 and internal standard are analysed by gas-liquid chromatography as the N-propionyl derivatives using a nitrogen-specific detector. Concentrations of HP 505 can be measured over the range 2-100 ng/ml plasma. The method has been applied to the analysis of biological fluids from volunteers receiving oral doses of HP 505.


Corneal staining in hydrogel lens wearers.
The purpose of this study was to determine the factors that contribute to corneal staining in hydrogel lens wearers by examining the following variables: type of lens worn, wearing time and lens replacement schedule, lens care system, and topical and systemic medication use. Five hundred full-time, successful hydrogel contact lens wearers were evaluated for corneal fluorescein staining at 20 clinical sites. Corneal staining was evaluated in five regions and was graded on a scale of 0 (no staining) to 4 (severe staining) in 0.5 steps for severity. Corneal fluorescein staining was present in at least one eye in 55.7% of the hydrogel lens wearers examined in this study, and 8.0% had moderate-to-severe staining (defined as a cumulative staining score of > or = 3 with at least one quadrant score > or = 2). Staining was most severe for the inferior portion of the cornea (mean +/- SD; OD: 0.34 +/- 0.57, OS: 0.30 +/- 0.54). All other areas of the cornea showed lesser amounts of staining, all of which were approximately equal (mean range, 0.13 to 0.16). Staining was observed in two or more quadrants in 24% of right eyes and 22.4% of left eyes. When questioned about care system compliance, 81.1% of subjects reported compliance. Patients who were noncompliant with their lens care system (chi 2 p = 0.0037), used rewetting drops (chi 2 p = 0.0005), or wore conventional lenses without a planned replacement schedule (chi 2 p = 0.0008) were more likely to have some degree of corneal staining. Noncompliance with care system (chi 2 p = 0.0147), replacement schedule (chi 2 p = 0.0039), and lens power (chi 2 p = 0.0224) were associated with moderate-to-severe staining. The following factors were not significantly associated with corneal staining: patient age, gender, medication use including oral contraceptives, type of wear (extended, flexible, or daily), average wearing time, wearing time at the examination, lens type (spherical or toric), water content of lenses (high or low water content), type of care system, use of enzymes, and pinching the contact lens directly off the cornea. Staining occurs to some extent in many hydrogel contact lens patients, and is influenced by many factors. Moderate-to-severe staining, which may be more clinically significant, is associated with noncompliance with care system, a conventional replacement schedule, and lens power.


Studies of the in vivo catabolism of exogenous dopamine as infused through a push-pull cannula implanted in the rat caudate nucleus.
In this report, using a push-pull perfusion technique, we examined in vivo the effects of exogenous dopamine (DA) on the output of neurochemical substances from the caudate nucleus (CN) of freely behaving rats. Exogenous DA, at concentrations of 10(-5) M, 5 x 10(-5) M and 10(-4) M, in modified Krebs-Ringer phosphate medium (KRP) was infused directly into the CN for 15 min each. Exogenous DA at the doses tested elicited increases in 3,4-dihydroxyphenylacetic acid (DOPAC) output in a dose-dependent manner. In addition, the higher two doses of exogenous DA also induced increases in homovanillic acid (HVA) output from the rat CN. The increases in DOPAC output by 5 x 10(-5) M DA was partially blocked by the inclusion of 10(-3) M nomifensine in KRP. Interestingly, exogenous DA-induced increases in HVA output were little affected by the nomifensine treatment. However, the catabolism of exogenous DA was almost completely eliminated by a prior 6-hydroxydopamine lesion in the ipsilateral substantia nigra. Furthermore, infusions of exogenous DA did not change 5-hydroxyindoleacetic acid output from the CN. In conclusion, our results confirm in vivo that (a) DA catabolic pathway via DOPAC intermediate predominates over the alternative pathway via 3-methoxytyramine, (b) increases in extracellular DA will lead to increases in DOPAC and HVA levels in extracellular space and (c) the majority of the DA is oxidized by intradopaminergic monoamine oxidase.


Flow on the symmetry plane of a total cavo-pulmonary connection.
The flow inside a total cavo-pulmonary connection, a bypass operation of the right heart adopted in the presence of congenital malformation, is here studied for a specific geometry which has been recently introduced in clinics. The analysis has been performed by preliminary experimental observation and a novel Navier-Stokes formulation on the symmetry plane. This method, once some basic hypotheses are verified, allows to reproduce the flow on the symmetry plane of a three-dimensional field by using an extension of the two-dimensional approach. The analysis has confirmed the existence of a central vortex showing that it is not a real vortex (i.e. a place with accumulation of vorticity) but, rather, a weakly dissipative recirculating zone. It is surrounded by a shear layer that becomes spontaneously unsteady at moderately high Reynolds number. The topological changes and energy dissipation have been analysed in both cases of unbalanced and of balanced pulmonary artery and caval flows.


Optimization and application of a high-resolution melting protocol in the characterization of avian infectious laryngotracheitis virus.
A previous sequence analysis of a US5 gene fragment of infectious laryngotracheitis virus (ILTV) performed in an Argentinian epidemiological study allowed to differentiate between wild and vaccine strains. This analysis also defined five ILTV haplotypes with specific variations at positions 461, 484, 832, 878 and 894 of the US5 gene. This characterization of viral strains may also be accomplished using the High-Resolution Melting Analysis (HRMA), which has been described as an effective, fast and sensitive method to detect mutations in PCR products. In the present study, an HRM protocol was developed with the aim of characterizing the circulating ILTV strains in Argentina. The specificity of this tool was confirmed in different DNA diluents, without interference from heterologous DNA or other cellular metabolites. Additionally, the salt concentration in the elution buffer used for DNA extraction did not alter the curve profiles. Higher concentrations of DNA (Ct≅26.0) displayed well-defined curve profiles, whereas lower concentrations (Ct≅32.5) exhibited more heterogeneous curves. The HRMA showed 97.49% concordance with the reference technique, i.e., sequencing. The HRM protocol has the capability to perform DNA amplification prior to its characterization. Thus, eventually this technique may be used simultaneously as a diagnostic tool. This advantage implies a significant reduction in the time and effort involved in sample processing.


Selective Vulnerability of Cancer Cells by Inhibition of Ca(2+) Transfer from Endoplasmic Reticulum to Mitochondria.
In the absence of low-level ER-to-mitochondrial Ca(2+) transfer, ATP levels fall, and AMPK-dependent, mTOR-independent autophagy is induced as an essential survival mechanism in many cell types. Here, we demonstrate that tumorigenic cancer cell lines, transformed primary human fibroblasts, and tumors in vivo respond similarly but that autophagy is insufficient for survival, and cancer cells die while their normal counterparts are spared. Cancer cell death is due to compromised bioenergetics that can be rescued with metabolic substrates or nucleotides and caused by necrosis associated with mitotic catastrophe during their proliferation. Our findings reveal an unexpected dependency on constitutive Ca(2+) transfer to mitochondria for viability of tumorigenic cells and suggest that mitochondrial Ca(2+) addiction is a feature of cancer cells.


Association of ideomotor apraxia with lesion site, etiology, neglect, and functional independence in patients with first ever stroke.
Ideomotor apraxia (IMA) is characterized by the inability to correctly imitate hand gestures and voluntarily pantomime tool use. The relationship between IMA and characteristics of stroke has not been totally elucidated. This study aimed to find out associations between presence of IMA and stroke etiology, site of the lesions, neglect, and temporal and functional parameters of stroke in patients with first ever stroke. Thirty-nine patients with first ever stroke were included. Patients with severe cognitive deficits were excluded. Assessment tools included Ideomotor Apraxia Test, Functional Independence Measure (FIM), Brunnstrom recovery stages, Mini Mental Test (MMT), and star cancellation test. Etiology (hemorrhagic or ischemic) and site of stroke was assessed through brain imaging methods. Location and size of ischemic lesion was determined by using the Oxfordshire Community Stroke Project system. IMA was identified in 35.9% of the patients. Patients with IMA had significantly lower FIM scores both on admission and discharge (P = 0.001, P = 0.001). Presence of IMA was significantly associated with the presence of neglect (P = 0.004), total anterior circulation ischemia (TACI) (P < 0.001), and lower MMT scores (P < 0.001). Lesion site, patient age, time since onset, and stroke etiology had no impact on the presence of IMA. IMA was in concordance with poor cognitive and functional state and was not limited to left hemisphere lesions. The study revealed strong associations between IMA, neglect, and TACI. Every patient with stroke should be evaluated for the presence of IMA on admission to rehabilitation unit.


Is the adherence to the food practices recommended by the dietary guidelines for the Brazilian population associated with diet quality?
The Brazilian Food Guide (BFG)'s messages are mostly qualitative and focused on food practices, such as meal planning, cooking, and eating modes. This study sough to investigate whether the adherence to these food practices is aligned with diet quality. A quota-based subsample of the NutriNet-Brasil Cohort (n = 2052) completed the Food Practices Brazil Scale (FPBr), a 24-item scale assessing the adherence to healthy eating practices recommended by the BFG. Four possible frequency-based answers are given and a score ranging from 0 to 72 is calculated by summing them (FPBr-score). Data from web-based 24-h recalls were used for calculating the usual percentage of energy intake (%energy) of ten food groups based on the level of food processing: plant-based unprocessed or minimally processed foods; processed foods; ultra-processed foods; fruits; vegetables; whole grains; beans and other legumes; nuts; red meat; and table sugar. The association between quartiles of the FPBr-score and food groups' %energy was analysed through crude and adjusted linear regression models. Except for red meat, all the other food groups were linearly associated with the FPBr-score in the expected direction. For example, adjusted means for the %energy of plant-based unprocessed or minimally processed foods were 26.7% (CI95% 25.9-27.5) and 36.8% (CI95% 36.0-37.6) among those classified in the first and fourth quartiles of the FPBr-score, respectively. For ultra-processed foods, these percentages were 27.0 (CI95% 26.3-27.8) against 17.5 (CI95% 16.7-18.3). These results support the use of messages based on practices and behaviors in Food-Based Dietary Guidelines. At the same time, they call attention to the importance of policies that enable people to adopt healthier food practices.


Intratympanic gentamicin treatment in Meniere's disease: patients' experiences and outcomes.
The aim of this study was to assess the experiences and outcomes of patients receiving intratympanic gentamicin treatment for Ménière's disease in Norfolk, UK. This study was based on a retrospective questionnaire survey and a review of patients' medical records. Two district hospitals. All 29 patients treated between 1999 and 2001, with a minimum follow up of two years post-treatment, were included in the study. Twenty-three patients completed the questionnaires (79 per cent response rate). Glasgow benefit inventory (GBI) and vertigo symptom scale (VSS) scores, plus change in hearing thresholds. The mean GBI total score was +36, indicating substantial improvement in patients' overall quality of life following gentamicin treatment. The VSS scores demonstrated low levels of vertigo or unsteadiness in treated patients. Three patients suffered deterioration in their hearing thresholds following a single injection of gentamicin. However, 96 per cent of responders stated that they would be willing to have such treatment again, if necessary. Intratympanic gentamicin treatment ought to be offered to Ménière's patients suffering from disabling vertigo, with the proviso that they be made aware of the possibility of hearing deterioration.


An immunohistochemical study of the tissue bridging adult spondylolytic defects--the presence and significance of fibrocartilaginous entheses.
Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament-i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic gap.


Microbial Diversity and Community Structure in Two Different Agricultural Soil Communities.
Abstract In this study, two different agricultural soils were investigated: one organic soil and one sandy soil, from Stend (south of Bergen), Norway. The sandy soil was a field frequently tilled and subjected to crop rotations. The organic soil was permanent grazing land, infrequently tilled. Our objective was to compare the diversity of the cultivable bacteria with the diversity of the total bacterial population in soil. About 200 bacteria, randomly isolated by standard procedures, were investigated. The diversity of the cultivable bacteria was described at phenotypic, phylogenetic, and genetic levels by applying phenotypical testing (Biolog) and molecular methods, such as amplified rDNA restriction analysis (ARDRA); hybridization to oligonucleotide probes; and REP-PCR. The total bacterial diversity was determined by reassociation analysis of DNA isolated from the bacterial fraction of environmental samples, combined with ARDRA and DGGE analysis. The relationship between the diversity of cultivated bacteria and the total bacteria was elucidated. Organic soil exhibited a higher diversity for all analyses performed than the sandy soil. Analysis of cultivable bacteria resulted in different resolution levels and revealed a high biodiversity within the population of cultured isolates. The difference between the two agricultural soils was significantly higher when the total bacterial population was analyzed than when the cultivable population was. Thus, analysis of microbial diversity must ultimately embrace the entire microbial community DNA, rather than DNA from cultivable bacteria.


An age-related axon terminal pathology around the first olfactory relay that involves amyloidogenic protein overexpression without plaque formation.
The glomeruli are the first synaptic relay on the olfactory pathway and play a basic role in smell perception. Glomerular degeneration occurs in humans with age and in Alzheimer's disease (AD). The glomeruli heavily express β-amyloid precursor protein (APP), β-secretase (BACE1) and γ-secretase complex. However, extracellular β-amyloid peptide (Aβ) deposition occurs fairly rarely at this location in postmortem pathological studies. We sought to explore age-related glomerular changes that might link to alteration in amyloidogenic proteins and/or plaque pathogenesis in transgenic models of AD and humans. Focally increased BACE1 immunoreactivity (IR) in the glomerular layer was identified in several transgenic models, and characterized systematically in transgenic mice harboring five familiar AD-related mutations (5XFAD). These elements were co-labeled with antibodies against APP N-terminal (22C11) and Aβ N-terminal (3D6, 6E10) and mid-sequence (4G8). They were not co-labeled with two Aβ C-terminal antibodies (Ter40, Ter42), nor associated with extracellular amyloidosis. These profiles were further characterized to be most likely abnormal olfactory nerve terminals. Reduced glomerular area was detected in 6-12-month-old 5XFAD mice relative to non-transgenic controls, and in aged humans relative to young/adult controls, more robust in AD than aged subjects without cerebral amyloid and tau pathologies. The results suggest that olfactory nerve terminals may undergo age-related dystrophic and degenerative changes in AD model mice and humans, which are associated with increased labeling for amyloidogenic proteins but not local extracellular Aβ deposition. The identified axon terminal pathology might affect neuronal signal transmission and integration at the first olfactory synaptic relay.


Pore-forming activity of the Tsx protein from the outer membrane of Escherichia coli. Demonstration of a nucleoside-specific binding site.
The Tsx protein from the outer membrane of Escherichia coli is known to be involved in the permeation of nucleosides across the outer membrane under limiting substrate conditions. We purified Tsx from an E. coli strain that overproduces Tsx. The purified protein was still functional since it could neutralize the Tsx-specific bacteriophage T6 in vitro. When the purified Tsx was reconstituted into a lipid bilayer, there was a large increase of the membrane conductance, indicating pore-forming activity of Tsx in vitro. This increase could be strongly blocked with adenosine and to a much lesser extent with cytidine. Titration of the pore conductance with adenosine or cytidine suggested the presence of a binding site for nucleosides in the Tsx pore, with a Ks of 6 X 10(-4) and 2 X 10(-2) M for adenosine and cytidine, respectively. We propose that the Tsx protein functions in vivo as a pore that specifically facilitates the permeation of nucleosides across the outer membrane due to its binding site for nucleosides.


Enzymatic synthesis of p-nitrophenyl N,N',N'',N'',N''''-pentaacetyl-beta-chitopentaoside in water-methanol system; significance as a substrate for lysozyme assay.
Transchitooligosylation from (GlcNAc)5 to the 4-position of PNP-GlcNAc was efficiently induced through lysozyme catalysis in an aqueous solution containing methanol with a high concentration. Use of the aqueous methanol system in this reaction not only guaranteed solubility of PNP-GlcNAc substrate, but also resulted in a remarkable increase in PNP-(GlcNAc)5 production. PNP-(GlcNAc)5 was substrate for lysozyme assay compared with PNP-(GlcNAc)4.


Autoinhibition of c-Abl.
Despite years of investigation, the molecular mechanism responsible for regulation of the c-Abl tyrosine kinase has remained elusive. We now report inhibition of the catalytic activity of purified c-Abl in vitro, demonstrating that regulation is an intrinsic property of the molecule. We show that the interaction of the N-terminal 80 residues with the rest of the protein mediates autoregulation. This N-terminal "cap" is required to achieve and maintain inhibition, and its loss turns c-Abl into an oncogenic protein and contributes to deregulation of BCR-Abl.


The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity.
Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at approximately 700 microM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.


Neutralization of hepatitis B virus (HBV) by human monoclonal antibody against HBV surface antigen (HBsAg) in chimpanzees.
The virus neutralizing efficacy of HB-C7A, a human monoclonal antibody raised against the surface antigen of hepatitis B virus (HBsAg), was proved using hepatitis B virus (HBV)-naïve chimpanzees. One control chimpanzee which received 100CID(50) of HBV, subtype adw, without HB-C7A antibody became infected by HBV as evidenced by the appearance of HBV DNA on week 10 and subsequent appearance of HBsAg, anti-HBc and anti-HBs in the serum. Two experimental chimpanzees were inoculated intravenously with same dose of HBV as the control chimpanzee, which was previously incubated with 0.1mg and 10mg of HB-C7A antibody prior to inoculation. HBV infection was not observed in the antibody-treated chimpanzees during 12 months of follow-up, exhibiting neither detectable HBsAg nor anti-HBc antibody. This work demonstrates the neutralization of HBV by HB-C7A monoclonal antibody and shows the possibility of prevention of HBV infection using this antibody in liver transplantation and exposure to HBV.


Joint and bone involvement in Swedish patients with Ixodes ricinus-borne Borrelia infection.
The presence of signs of joint involvement was investigated in 231 patients with erythema chronicum migrans Afzelius (ECMA), in 50 patients with acrodermatitis chronica atrophicans (ACA), in four patients with spirochete-induced facial palsy and in one patient with pericarditis and serologic evidence of Borrelia spirochetal infection. Only one of 16 untreated patients with ECMA developed arthritis. The patient with pericarditis had suffered from arthritis for 2 months when the cardiac symptoms developed. Thirteen of the patients with ACA had luxations/subluxations of small joints in the hands or feet and/or arthritis in large joints. In four of the patients with ACA, periosteal thickening of bones was found. The results indicate that joint abnormalities are not uncommon in patients with ACA. However, arthritis during the first year of tick-borne spirochetal infection was less common in Sweden than has been reported among patients with Lyme disease in the United States.


Evaluation of a novel high-resolution mapping technology for ablation of recurrent scar-related atrial tachycardias.
Rhythmia is a new technology capable of rapid and high-resolution mapping. However, its potential advantage over existing technologies in mapping complex scar-related atrial tachycardias (ATs) has not yet been evaluated. The purpose of this study was to examine the utility of Rhythmia for mapping scar-related ATs in patients who had failed previous ablation procedure(s). This multicenter study included 20 patients with recurrent ATs within 2 years after a previous ablation procedure (1.8 ± 0.7 per patient). In all cases, the ATs could not be adequately mapped during the index procedure because of scar with fractionated electrograms, precluding accurate time annotation, frequent change in the tachycardia in response to pacing, and/or degeneration into atrial fibrillation. These patients underwent repeat mapping and ablation procedure with Rhythmia. From a total of 28 inducible ATs, 24 were successfully mapped. Eighteen ATs (75%) terminated during radiofrequency ablation and 4 (16.6%) with catheter pressure or entrainment from the site of origin or isthmus. Two ATs that were mapped to the interatrial septum slowed but did not terminate with ablation. In 21 of 24 ATs the mechanism was macroreentry, while in 3 of 24 the mechanism was focal. Interestingly, in 5 patients with previously failed ablation of an allegedly "focal" tachycardia, high-resolution mapping demonstrated macroreentrant arrhythmia. The mean mapping time was 28.6 ± 17 minutes, and the mean radiofrequency ablation time to arrhythmia termination was 3.2 ± 2.6 minutes. During a mean follow-up of 7.5 ± 3.1 months, 15 of 20 patients (75%) were free of AT recurrences. The Rhythmia mapping system may be advantageous for mapping complex scar-related ATs.


Determination of inorganic chemical parameters in drinking water in districts of the province of Puno in the region Puno-Peru.
The inorganic chemical parameters in drinking water that include heavy metals are substances that exist in nature very widespread, nevertheless toxic metals such as lead, cadmium, arsenic, mercury, are very harmful to human health and to all forms of life, these toxic metals are silents contaminants. Therefore, the present study aims to determine the presence of inorganic chemical parameters in the drinking water from districts of the province of Puno. The results were compared based on the parametric test T-student and the non-parametric tests Kolmogorov-Smirnov. Finding the highest values (mg/L) in districts as Capachica Ba (0.8458) and Pb (0.5255), Mañazo Al (3.08) and Pb (0.0185), San Antonio de Esquilache Fe (0.49) and Pb (0.9513), Vilque As (0.0193) and Pb (15.34), and Pichacani As (0.0193) and Pb (0.0215), as it is observed the samples do not comply with the regulation of the quality of drinking water in Peru, making it unsuitable for human consumption.


Parameter extraction from heart rate and arterial blood pressure variability signals in dogs for the validation of a physiological model.
The paper describes an automatic procedure for improving the extraction of parameters in heart rate (HR) and arterial blood pressure (ABP) beat-to-beat variability signals. Auto- and cross-spectral analysis of such signals is carried out through parametric models and the distribution of the power of the spectra and the phase relationships are compared in various physiological situations induced in the dogs via drug infusion or surgical interventions which do influence the control mechanisms of HR and ABP. This "black-box" approach allows the obtention, directly from the processing of the above-mentioned signals, of the estimation of parameters relative to cardiovascular models, as the ones described by simple equations (Windkessel and Starling laws are introduced as examples). These parameters seem to validate significantly the capability of such models to describe the physiological interactions existing between the two considered signals. Applications may be foreseen both for research and clinical purposes.


Comparison of the ability of feline calicivirus (FCV) vaccines to neutralise a panel of current UK FCV isolates.
Feline calicivirus (FCV) comprises a large number of strains which are related antigenically to varying degrees. The antigenic variability creates problems for choosing antigens to include in vaccines. Historically, these have been selected for use based on their cross-reactivity with a high proportion of field strains. However, it is important to determine the current level of cross-reactivity of vaccines and whether or not this may be decreasing owing to widespread vaccine use. In this in vitro study, we have compared the ability of antisera to two vaccine viruses (FCV strain F9 and FCV strain 255) to neutralise a panel of 40 recent UK field isolates. These 40 isolates were obtained by randomised, cross-sectional sampling of veterinary practices in different geographical regions of the UK so as to ensure they were representative of viruses circulating in the veterinary-visiting population of cats in the UK. Virus neutralisation assays showed that both vaccine strains are still broadly cross-reactive, with F9 antiserum neutralising 87.5% and 255 antiserum 75% of isolates tested with antiserum dilutions of 1 in 2 or greater. However, when antibody units were used, in order to take account of differences in homologous titres between antisera, fewer isolates were neutralised, with F9 antiserum showing a slightly higher proportion of isolates neutralised than 255. Multivariable analysis of the sample population of 1206 cats from which the 40 isolates were derived found that vaccinated cats were at a decreased risk of being positive for FCV, whereas cats from households with more than one cat, and cats with mouth ulcers were at increased risk. In addition as cats became older their risk of shedding FCV decreased.


Why halides enhance heterogeneous metal ion charge transfer reactions.
The reaction kinetics of many metal redox couples on electrode surfaces are enhanced in the presence of halides (i.e., Cl-, Br-, I-). Using first-principles metadynamics simulations, we show a correlation between calculated desorption barriers of V3+-anion complexes bound to graphite via an inner-sphere anion bridge and experimental V2+/V3+ kinetic measurements on edge plane pyrolytic graphite in H2SO4, HCl, and HI. We extend this analysis to V2+/V3+, Cr2+/Cr3+, and Cd0/Cd2+ reactions on a mercury electrode and demonstrate that reported kinetics in acidic electrolytes for these redox couples also correlate with the predicted desorption barriers of metal-anion complexes. Therefore, the desorption barrier of the metal-anion surface intermediate is a descriptor of kinetics for many metal redox couple/electrode combinations in the presence of halides. Knowledge of the metal-anion surface intermediates can guide the design of electrolytes and electrocatalysts with faster kinetics for redox reactions of relevance to energy and environmental applications.


Adenosine as a Multi-Signalling Guardian Angel in Human Diseases: When, Where and How Does it Exert its Protective Effects?
The importance of adenosine for human health cannot be overstated. Indeed, this ubiquitous nucleoside is an integral component of ATP, and regulates the function of every tissue and organ in the body. Acting via receptor-dependent and -independent mechanisms [the former mediated via four G-protein-coupled receptors (GPCRs), A1, A2A, A2B, and A3,], it has a significant role in protecting against cell damage in areas of increased tissue metabolism, and combating organ dysfunction in numerous pathological states. Accordingly, raised levels of adenosine have been demonstrated in epilepsy, ischaemia, pain, inflammation, and cancer, in which its behaviour can be likened to that of a guardian angel, even though there are instances in which overproduction of adenosine is pathological. In this review, we condense the current body of knowledge on the issue, highlighting when, where, and how adenosine exerts its protective effects in both the brain and the periphery.


Breast cancer risk factors according to joint estrogen receptor and progesterone receptor status.
We investigated risk factor patterns for subtypes of breast cancer characterized by joint estrogen receptor (ER) and progesterone receptor (PR) status in a hospital-based case-control study. ER and PR tumor status were determined immunohisotchemically. Risk factors of interest were entered into a multiple polychotomous logistic regression model simultaneously; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Using this model, cases in the four tumor subtypes (ER+PR+, ER-PR-, ER+PR-, ER-PR+) were compared simultaneously to controls. A Wald test for heterogeneity across the four subtypes was conducted, as well as a case-case comparison between the two most biologically disparate subtypes, ER+PR+ and ER-PR-. The receptor status distribution was as follows: 33% ER+PR+, 34% ER-PR-, 20% ER+PR-, and 13% ER-PR+. Among 317 cases and 401 controls, we found significant heterogeneity across the four tumor subtypes for older age at first full-term pregnancy (p=0.04) and post-menopausal status (p=0.04). For older age at first full-term pregnancy, an elevated risk was found for the ER+PR- subtype (OR=2.5; 95% CI: 1.2-5.1). For post-menopausal status, elevated risks were found for both the ER+PR+ (OR=2.4; 95% CI: 1.1-4.9) and ER+PR- (OR=7.2; 95% CI: 2.4-21.7) subtypes. From the case-case comparisons, we found that cases, who had consumed alcohol for more than 1 year were 3.4 times more likely to have ER+PR+ tumors than ER-PR- tumors (95% CI: 1.4-8.4). Certain breast cancer risk factors may vary by ER and PR status, and joint ER/PR status should be taken into account in future studies of risk factor estimates.


Identification of schizophrenia symptom-related gene modules by postmortem brain transcriptome analysis.
Schizophrenia is a multifactorial disorder, the genetic architecture of which remains unclear. Although many studies have examined the etiology of schizophrenia, the gene sets that contribute to its symptoms have not been fully investigated. In this study, we aimed to identify each gene set associated with corresponding symptoms of schizophrenia using the postmortem brains of 26 patients with schizophrenia and 51 controls. We classified genes expressed in the prefrontal cortex (analyzed by RNA-seq) into several modules by weighted gene co-expression network analysis (WGCNA) and examined the correlation between module expression and clinical characteristics. In addition, we calculated the polygenic risk score (PRS) for schizophrenia from Japanese genome-wide association studies, and investigated the association between the identified gene modules and PRS to evaluate whether genetic background affected gene expression. Finally, we conducted pathway analysis and upstream analysis using Ingenuity Pathway Analysis to clarify the functions and upstream regulators of symptom-related gene modules. As a result, three gene modules generated by WGCNA were significantly correlated with clinical characteristics, and one of these showed a significant association with PRS. Genes belonging to the transcriptional module associated with PRS significantly overlapped with signaling pathways of multiple sclerosis, neuroinflammation, and opioid use, suggesting that these pathways may also be profoundly implicated in schizophrenia. Upstream analysis indicated that genes in the detected module were profoundly regulated by lipopolysaccharides and CREB. This study identified schizophrenia symptom-related gene sets and their upstream regulators, revealing aspects of the pathophysiology of schizophrenia and identifying potential therapeutic targets.


Radiological changes with magnetic resonance imaging and computed tomography after irradiating minipig mandibles: The role of T2-SPIR mixed signal intensities in the detection of osteoradionecrosis.
Radiotherapy in the head and neck can induce several radiologically detectable changes in bone, osteoradionecrosis (ORN) among them. The purpose is to investigate radiological changes in mandibular bone after irradiation with various doses with and without surgery and to determine imaging characteristics of radiotherapy and ORN in an animal model. Sixteen Göttingen minipigs were divided into groups and were irradiated with two fractions with equivalent doses of 0, 25, 50 and 70 Gray. Thirteen weeks after irradiation, left mandibular teeth were removed and dental implants were placed. CT-scans and MR-imaging were made before irradiation and twenty-six weeks after. Alterations in the bony structures were recorded on CT-scan and MR-imaging and scored by two head-neck radiologists. Increased signal changes on MR-imaging were associated with higher radiation doses. Two animals developed ORN clinically. Radiologically mixed signal intensities on T2-SPIR were seen. On CT-scans cortical destruction was found in three animals. Based on imaging, three animals were diagnosed with ORN. Irradiation of minipig mandibles with various doses induced damages of the mandibular bone. Imaging with CT-scan and MR-imaging showed signal and structural changes that can be interpreted as prolonged and insufficient repair of radiation induced bone damages.


LncRNA SPRY4-IT1 regulates breast cancer cell stemness through competitively binding miR-6882-3p with TCF7L2.
SPRY4-intronic transcript 1 has been found in several kinds of cancers, but the role of SPRY4-IT1 in breast cancer stem cells has not been studied. We investigated whether SPRY4-IT1 is involved in the promotion of breast cancer stem cells (BCSCs). We used qRT-PCR to detect the expression of SPRY4-IT1 in MCF-7 cells and MCF-7 cancer stem cells (MCF-7 CSCs). The effects of SPRY4-IT1 on the proliferation and renewal ability of breast cancer cells were investigated by in vitro and in vivo assays (ie in situ hybridization, colony formation assay, sphere formation assay, flow cytometry assay, western blotting, xenograft model and immunohistochemistry). The mechanism of SPPRY4-IT1 as a ceRNA was studied by a dual-luciferase reporter assay and bioinformatic analysis. In our study, SPRY4-IT1 was up-regulated in MCF-7 CSCs compared with MCF-7 cells, and high SPRY4-IT1 expression was related to reduced breast cancer patient survival. Furthermore, SPRY4-IT1 overexpression promoted breast cancer cell proliferation and stemness in vitro and in vivo. In addition, SPRY4-IT1 knockdown suppressed BCSC renewal ability and stemness maintenance in vivo and in vitro. The dual-luciferase reporter assays indicated that SPRY4-IT1 as a sponge for miR-6882-3p repressed transcription factor 7-like 2 (TCF7L2) expression. Taken together, these findings demonstrated that SPRY4-IT1 promotes proliferation and stemness of breast cancer cells as well as renewal ability and stemness maintenance of BCSCs by increasing the expression of TCF7L2 through targeting miR-6882-3p.


4-Aminopyridine enhances motor evoked potentials following graded spinal cord compression injury in rats.
Although several experimental and clinical studies have demonstrated the ability of 4-aminopyridine (4-AP) to restore electrophysiological and/or behavioral function following chronic spinal cord injury, the mechanism by which this occurs remains unclear. Demonstration of efficacy in rat spinal cord injury has not been reported, evidently because even relatively mild spinal cord contusions that produce only minor permanent locomotor disturbances abolish hind limb myoelectric motor evoked potentials (mMEPs). In this study, mMEPs were recorded acutely 25 days following graded thoracic spinal cord compression in rats. mMEP amplitudes were significantly enhanced by a single, 2 mg/kg i.v. dose of 4-AP. mMEPs were increased in all rats showing some evoked responses initially, and also in some animals which had no responses prior to treatment. 4-AP was further found to increase the maximum following frequency of mMEPs in both normal and injured rats from about 0.1 Hz to between 1 and 10 Hz. These data suggest that 4-AP might act by enhancing synaptic efficacy, as well as enhancing conduction in spinal axons whose myelination has been rendered dysfunctional by trauma.


NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression.
Although ARF can suppress tumor growth by activating p53 function, the mechanisms by which it suppresses tumor growth independently of p53 are not well understood. Here, we identified ARF as a key regulator of nuclear factor E2-related factor 2 (NRF2) through complex purification. ARF inhibits the ability of NRF2 to transcriptionally activate its target genes, including SLC7A11, a component of the cystine/glutamate antiporter that regulates reactive oxygen species (ROS)-induced ferroptosis. As a consequence, ARF expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. Moreover, the ability of ARF to induce p53-independent tumor growth suppression in mouse xenograft models is significantly abrogated upon NRF2 overexpression. These results demonstrate that NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses.


Inactivating chromosomes: a macro domain that minimizes transcription.
The histone variant macroH2A plays a role in mammalian chromosome X inactivation. Recent data suggest its unusual C-terminal macro domain may be an enzyme that regulates the ADP-ribosylation of chromatin. MacroH2A could thus help correct gene dosage between males and females using a novel epigenetic mark.


Prevalence of a shortened prostacyclin half-life in plasma in healthy adults: results of a screening investigation.
Out of a total of 1,981 adults (956 males, 1,025 females; aged 16-71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half-life in these three screenings was shorter than 60 sec and persisted during several follow-up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half-life of PG12 in 1,978 people amounted to 10.71 +/- 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons.


Spontaneous common bile duct perforation presenting as acute abdomen.
Spontaneous common bile duct (CBD) perforation is an unusual cause of acute abdomen. It is rarely suspected or correctly diagnosed preoperatively. Clinical presentation is as biliary peritonitis. The common causes are CBD calculus disease, tumors of the bile duct, choledochal cyst and sometimes idiopathic. Treatment is surgical and consists of CBD exploration and repair over a T tube.


Indentations in the terminal cisternae of slow- and fast-twitch muscle fibers from normal and paraplegic rats.
Indentations in the terminal cisternae were measured in freeze-fracture replicas of extensor digitorum longus (EDL) and soleus muscles from normal rats and from rats in which the spinal cord had been transected at the midthoracic level 6 weeks earlier. The density of indentations was compared with contraction time and characteristics of K-contractures. In paraplegic rats, the average soleus contraction time decreased from 89 to 46 msec and the average number of indentations, per micrometer of terminal cisternae, increased from 0.9 to 5.0. The EDL contraction time decreased from 35 to 31 msec and the indentations increased from 7.3 to 8.1. In spite of the considerable scatter in the data, there was a clear correlation between indentation density and contraction time. Similarly, indentation density was correlated with the voltage dependence of tension generated during K-contractures. The results show that the density of indentations can be modulated by afferent neural activity and support the hypothesis that indentations play an important role in excitation-contraction coupling.


Bile acid metabolism in human hyperthyroidism.
Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry. Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 +/- 33 vs. 261 +/- 51 mg per dl, p less than 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 +/- 2.8 vs. 7.9 +/- 4.2 mu moles per kg per day, p less than 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 +/- 3.4 vs. 22.0 +/- 5.2 mu moles per kg, p less than 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum. The depression of cholic acid synthesis in the presence of unaltered subjects is compatible with an inhibition of hepatic 12 alpha-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.


Relationship between neck motion and self-reported pain in patients with whiplash associated disorders during the acute phase.
Biomechanical measures quantify motor control and functional deficits in Whiplash Associated Disorders (WAD), but few studies relate those measures to the clinical scales that are routinely used to assess patients. Most studies are limited to chronic neck pain, and report poor to moderate correlations. To define a statistical model that relates measures of neck kinematics with clinical scales of neck pain, in WAD patients during the rehabilitation process in the acute phase (less than 3 months since the accident). 96 WAD patients self-assessed their pain using VAS and NPQ, and passed neck motion tests as part of their rehabilitation program. Four regression models were fitted to analyze the effects of the measured kinematic parameters and subject-specific characteristics on VAS and NPQ. Model errors were compared to minimal clinically significant differences. Multiple correlation coefficients of the models were between 0.74 and 0.90. More than 66% of that correlation was accounted for by subject-specific factors, and most of the other half by the measured kinematic parameters. Range of motion of flexion-extension and axial rotation, and harmonicity of flexion-extension, where the variables most consistently related to the decrease of pain. The error of the models was within the MCSD in more than 50% of the observations. Part of the individual progression of pain and pain-related disability in acute WAD patients, as rated by NPQ and VAS, can be mapped to objective kinematic parameters of neck mobility tests, like ranges of motion, velocities, repeatability and harmonicity of movements.


The intestinal phosphate transport under condition of experimental hypercalcemia.
The analysis of the serum calcium and phosphate level changes in intact Vitamin D--dosed animals showed the increasing serum calcium values without any concomitant change in serum phosphate concentration. The observed discrepancy of intestinal phosphate transport in vitro and in vivo studies together with the effect of Vitamin D towards normalizing serum phosphate level in TPTX Vitamin D--dosed animals suggest the presence of Vitamin D as some phosphate regulatory factor. The participation of the possible role of 25 OH D3 in the observed phenomenon is under current investigations. In PTH supressed hypercalcemic conditions we did not reproduce, with the usage of 1alpha--OH D3, the regulatory effect of 1,25 (OH) 2D3 described by Garabedian et al. /1/.


An in vivo preparation (Thiry-Vella fistula) suitable for the measurement of intestinal absorption in the guinea pig.
A thiry-Vella isolated intestinal loop was constructed in the guinea pig. The procedure consisted of removal of a 30-cm segment of the jejunem, restoration of intestinal continuity by a jejunojejunostomy, and exteriorization of the segment through stomata sutured to the skin. The procedure was performed on seven guinea pigs of which three survived. The three survivors remained normal in maintenance of hair, feeding, and weight gain over a long period.


The Perpendicular Extraction - Visionary Concept with the Prospect of Generating the Perfect Extraction of Teeth, or a Misguided Vision that had to Fail Due to Anatomical Circumstances?
From the second half of the 18th century to the last third of the 19th century, a period of about 100 years, perpendicular (vertical) extraction, became an ideal for many authors, since molars were the most difficult teeth to remove. However, extraction instruments available at that time, caused pronounced damage to the alveolar bone and gingiva. For many authors and clinicians, vertical extraction was the only way to meet this challenge. This approach to tooth removal, while viable, came to an end when anatomically shaped forceps, adapted to the different morphologies of the various teeth were introduced, thereby changing 19th century dentistry with a new standard for tooth removal.


Everyday dietary behaviour and the relationship between attention and meal size.
Previously, it has been demonstrated that overeating can occur when an individual engages in a cognitive task during a meal. One possibility, therefore, is that task performance can provide a measure of attention to dietary control. To explore this idea we measured performance on an otherwise irrelevant task during a meal. In two experiments, we compared intake and performance across five groups of females; dieters, and four groups of non-dieters, each with contrasting high and low scores on the restraint scale of the Dutch Eating Behaviour Questionnaire and the disinhibition scale of the Three-Factor Eating Questionnaire. Our analysis suggests that a correspondence can exist between task performance and intake (Experiment 1) and this might be influenced by the extent to which foods are regarded as forbidden (Experiment 2). However, aspects of our data are difficult to reconcile with the idea that task performance reflects a simple measure of attention to dietary control. Instead, one possibility is that individuals differ in the way that they choose to allocate attention during a meal. In relation to this idea, we discuss the possibility that some individuals choose to avoid food-related cognition by engaging strategically with other aspects of their cognitive environment.


Association of triiodothyronine levels with left ventricular function, cardiovascular events, and mortality in hemodialysis patients.
Hemodialysis (HD) patients have altered free triiodothyronine (fT3) levels. A low fT3 level is a strong and inverse mortality predictor in HD patients. However, little is known about the relationship between fT3 and left ventricular function in HD patients. A total of 128 maintenance HD patients were enrolled in this study. A thyroid function test with blood sampling and echocardiography was conducted. Low-T3 syndrome was defined as fT3 level <3.62 pmol/L and normal thyroid stimulating hormone (TSH). Overall mortality and rate of cardiovascular (CV) events were assessed during 48 months of follow-up. Low-T3 syndrome was detected in 57 (44.5%) of the 128 patients. Patients with low-T3 syndrome had a shorter duration of HD (49.1 vs. 73.3, p = 0.01), and lower serum albumin (35.1 vs. 40.4 g/L, p<0.001), left ventricular ejection fraction (LVEF; 54.7% vs. 63.9%, p<0.001), and fractional shortening at endocardial levels (endoFS; 29.3% vs. 34.8%, p = 0.001) compared to those with normal fT3 levels. In multivariate linear regression, LVEF, albumin, and duration of HD were independently correlated with fT3 levels. In addition, fT3 was also correlated with LVEF. During the study period, 13 (10.1%) patients died, CV events occurred in 15 (11.7%) patients. In Cox regression analysis, low fT3 level and elevated high-sensitivity C-reactive protein (hs-CRP) were associated with mortality and CV events. In HD patients, fT3 level is positively correlated with LVEF. Low fT3 level and elevated hs-CRP predicted all-cause mortality and CV events.


Molecular epidemiology and seroprevalence in asymptomatic Plasmodium falciparum infections of Malagasy pregnant women in the highlands.
Malaria epidemiology in Madagascar is classified into four different areas, ranging from unstable seasonal transmission in the highlands to hyperendemic perennial transmission areas in the costal level. Most malaria studies in Madagascar are focused on symptomatic children. However, because of the low transmission in some areas with correspondingly low level of semi-immunity, adults are also at risk, in particular pregnant women. The objective of this study was to gain information on the genetic epidemiology of malarial infections in pregnant women in order to provide information for malaria control and elimination programmes in Madagascar. Between May and August 2010, we carried out cross-sectional surveys targeting healthy pregnant women in six locations, three in the coastal area and three in the highlands at 850-1300 m. 1244 blood samples were screened for anti-Plasmodium falciparum antibodies by immunofluorescence test and for malarial infection by realtime-PCR. The prevalence of chloroquine and sulphadoxine-pyrimethamine resistance markers was also determined in all Plasmodium falciparum samples by PCR-RFLP as well as the multiplicity of infection through genotyping six neutral microsatellites. In the highlands, 67.4% of the women presented antibodies against Plasmodium falciparum and 9.2% were carrying parasites, at the coast 95.6% and 14.8%, respectively. In the mean, 1.2 clones were detected in infected pregnant woman in the highlands and 1.5 at the coast. A higher level of monoclonal infections was found in the highlands (85.4%) compared to the coast (61.8%). Resistance markers for sulphadoxine-pyrimethamine were present only in two sites. Immunity is triggered in Malagasy highland populations when they are infected with malaria parasites, but these populations could also serve as a reservoir for epidemics.


Bioinequivalence of erythromycin ethylsuccinate and enteric-coated erythromycin pellets following multiple oral doses.
Bioequivalence comparisons between erythromycin ethylsuccinate and an enteric-coated erythromycin base pellet product were made following multiple-dose, oral administration. Twenty-four volunteers participated in a ten-dose protocol (one dosage unit every six hours) using a complete crossover design. Plasma samples were assayed using a microbiological method specific for erythromycin base in the presence of the ester. Without correcting for the differences in doses administered, the amount of active erythromycin base absorbed from the enteric-coated pellet (250 mg base) was five to seven times that absorbed from the erythromycin ethylsuccinate product (400 mg base equivalent) at steady state. Erythromycin ethylsuccinate is not bioequivalent to an enteric-coated erythromycin base pellet product. The lower bioavailability of the ethylsuccinate may be due to instability in the acidic medium of the stomach.


[Comparative study of hormonal preparations by isoelectric focusing and polyacrylamide gel electrophoresis].
The authors studied the purity of the hormonal drugs by electrophoresis in polyacrylamide gel and isoelectrofocusing. Identified fractions found in insulin, glucagon, andecaline and in other preparations. Established that isoelectrofocusing has a higher separation power as compared with disc electrophoresis in polyacrylamide gel.


Is healthcare the new manufacturing?: Industry, gender, and "good jobs" for low- and middle-skill workers.
Using the 2004 and 2008 panels of the Survey for Income and Program Participation (SIPP), we examine whether the heavily feminized health care industry produces "good jobs" for workers without a college degree as compared to other major industries. For women, we find that jobs in the health care industry are significantly more likely than the food service and retail industries to provide wages above $15 per hour, health benefits, fulltime hours, and job security. Jobs in the health care industry are not "good jobs" for low- and middle-skill men in terms of wages, relative to the industries of construction and manufacturing, but health care jobs can provide men with greater job security, and in comparison to construction, a higher probability of employer-based health insurance. That said, the findings emphasize that because men and women are differentially distributed across industries, access to different forms of job quality is also gendered across industries, with important implications for gender dynamics and economic strain within working class families.