Occult biochemical pregnancy: fact or fiction?
Daily urine samples were obtained from 38 women of proven fertility, who were attempting to conceive, to assess the frequency of clinically unsuspected "biochemical pregnancies' on the basis of late luteal phase rises of hCG. In 25 clinically confirmed conception cycles, the earliest pregnancy-induced hCG rises from baseline occurred 8 days after the endocrinologically defined date of ovulation (mean 11.1 days, SD 1.3). Urine samples obtained throughout 50 non-conception ovulatory cycles provided no evidence of any 'biochemical pregnancies' on the basis of late luteal phase rises of hCG occurring 8 or more days after the endocrinologically defined date of ovulation. If, as in previous studies, the date of ovulation had been estimated on the basis of menstrual cycle length and only the relatively non-specific NIH antiserum had been used in RIAs, 7 of the 50 (14%) cycles would have been classified as resulting in biochemical pregnancies on the basis of hCG greater than 50 m-i.u./ml on one occasion or greater than 20 m-i.u./ml on two or more occasions after day 20 of the cycle. These levels of 'hCG' occurred at or soon after ovulation and could be explained by LH cross-reacting in the RIA. The rises of 'hCG' were not confirmed when the urine samples were retested with an antiserum (Wellcome 895) of very high specificity for hCG. These results raise the possibility that the frequency of clinically unsuspected 'biochemical pregnancy' may have been substantially overestimated.


Acute neuro-endocrine profile and prediction of outcome after severe brain injury.
The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome. Prospective study, including consecutive patients, 15-70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08-10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17-19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E. Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH- and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated. Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.


Hyaluronan substratum holds mesenchymal stem cells in slow-cycling mode by prolonging G1 phase.
We examined, in vitro, whether hyaluronan induces slow cycling in placenta-derived mesenchymal stem cells (PDMSCs) by comparing cell growth on a hyaluronan-coated surface with cell growth on a tissue-culture polystyrene surface. The hyaluronan-coated surface significantly downregulated the proliferation of PDMSCs, more of which were maintained in the G(0)/G(1) phases than were cells on the tissue-culture polystyrene surface. Both PKH-26 labeling and BrdU incorporation assays showed that most PDMSCs grown on a hyaluronan-coated surface duplicated during cultivation indicating that the hyaluronan-coated surface did not inhibit PDMSCs from entering the cell cycle. Mitotic synchronization showed that the G(1)-phase transit was prolonged in PDMSCs growing on a hyaluronan-coated surface. Increases in p27(Kip1) and p130 were the crucial factors that allowed hyaluronan to lengthen the G(1) phase. Thus, hyaluronan might be a promising candidate for maintaining stem cells in slow-cycling mode by prolonging their G(1)-phase transit.


Spatial and seasonal variations of the chemical, mineralogical and morphological features of quasi-ultrafine particles (PM 0.49) at urban sites.
Combining chemical and physical-structural information of particles is a key issue in PM investigations. Chemical, mineralogical, and morphological characterization of quasi-ultrafine particles (PM 0.49) was carried out at two urban sites of varying traffic-influence (roadside and urban background) in Thessaloniki, northern Greece, during the cold and the warm period of 2013. Bulk analyses of chemical species included organic and elemental carbon (OC, EC), water soluble organic carbon (WSOC), ionic species (NO3(-), SO4(2-), Cl(-), Na(+), NH4(+), K(+), Mg(2+), Ca(2+)) and trace elements (As, Ba, Cd, Cr, Cu, Fe, Pb, Mn, Ni, Zn, Pt, Pd, Rh, Ru, and Ir). X-ray diffractometry (XRD) was employed for the mineralogical analysis of PM 0.49 in order to identify and quantify amorphous and crystalline phases. In addition, scanning electron microscopy coupled with energy dispersive spectrometry (SEM-EDS) was employed for morphological characterization and elemental microanalysis of individual particles. Findings of this work could provide the basis for designing epidemiological and toxicity studies to mitigate population exposure to UFPs.


125I protein A: applications to the quantitative determination of fluid phase and cell-bound IgG.
An improved method for the preparation of 125I-labelled Protein A (125I PA) of high specific and functional activity is described. 125I PA has been used in combination with purified rabbit IgG bound to a solid support to develop a competitive binding assay capable of detecting Protein A or human, rabbit and guinea pig IgG at the nanogram level. An optimal set of assay conditions was established and levels of IgG measured in normal human, rabbit and strain-2 guinea pig serum. 125I PA has also been used to detect IgG anti-Forssman antibody bound to sheep erythrocytes and to line-1 and line-10 tumor cells and as an indirect assay for tumor associated antigen in the ascitic fluid of tumor-bearing guinea pigs.


Alterations of myocardial contraction associated with a structural heart defect in embryonic chicks.
Ablation of cardiac neural crest at stages 8-10 produces a structural heart defect (persistent truncus arteriosus, PTA) in embryonic chicks. PTA is associated with decreased myocardial contractility, as indicated by decreased left ventricular ejection fraction. We compared the force of small ventricular strips from normal and defective chick hearts. In intact muscle, ablation of the neural crest leads to a 30-50% decrease in twitch force at any level of extracellular Ca2+ (0.45-20 mM) at embryonic days (ED) 7 and 15, relative to sham-operated controls. These differences could reflect defects at the level of the contractile apparatus and/or in the excitation-contraction coupling process. To distinguish changes of the contractile apparatus, we used detergent skinned preparations. The maximal Ca(2+)-activated force (Fmax) at ED15 was not significantly different between control and experimental embryos. At ED 7, however, Fmax was reduced by 36% in experimental preparations. Electron-micrographs showed that the organization and orientation of the myofibrils was similar in experimental and control ventricles. At ED 14, however, the average myofibrillar diameter was significantly increased in experimental ventricles. The content of the major myofibrillar proteins (myosin heavy chain, actin, and tropomyosin), determined from polyacrylamide gel electrophoresis and Coomassie Blue staining, normalized to total protein, was not statistically different in experimental and control ventricles at ED7. At ED15, however, content of these proteins was doubled in experimental ventricles. These data suggest a possible defect of the contractile apparatus at both ED 7 and 15, since the ratio of Fmax/myosin is reduced in the experimental hearts.


An analysis of the severity and incident duration of truck-involved freeway accidents.
Data associated with over 9000 accidents involving large trucks and combination vehicles during a two-year period on freeways in the greater Los Angeles area are analyzed relative to collision factors, accident severity, and incident duration and lane closures. Relationships between type of collision and accident characteristics are explored using log-linear models. The results point to significant differences in several immediate consequences of truck-related freeway accidents according to collision type. These differences are associated both with the severity of the accident, in terms of injuries and fatalities, as well as with the impact of the accident on system performance, in terms of incident duration and lane closures. Hit-object and broadside collisions were the most severe types in terms of fatalities and injuries, respectively, and single-vehicle accidents are relatively more severe than two-vehicle accidents. The durations of accident incidents were found to be log-normally distributed for homogeneous groups of truck accidents, categorized according to type of collision and, in some instances, severity. The longest durations are typically associated with overturns.


Overtime work, job autonomy, and employees' subjective well-being: Evidence from China.
Chinese workers suffer more from overtime than in many countries. Excessive working hours can crowd out personal time and cause work-family imbalance, affecting workers' subjective well-being. Meanwhile, self-determination theory suggests that higher job autonomy may improve the subjective well-being of employees. Data came from the 2018 China Labor-force Dynamics Survey (CLDS 2018). The analysis sample consisted of 4,007 respondents. Their mean age was 40.71 (SD = 11.68), and 52.8% were males. This study adopted four measures of subjective well-being: happiness, life satisfaction, health status, and depression. Confirmation factor analysis was employed to extract the job autonomy factor. Multiple linear regression methods were applied to examine the relationship between overtime, job autonomy, and subjective well-being. Overtime hours showed weak association with lower happiness (β = -0.002, p < 0.01), life satisfaction (β = -0.002, p < 0.01), and health status (β = -0.002, p < 0.001). Job autonomy was positively related to happiness (β = 0.093, p < 0.01), life satisfaction (β = 0.083, p < 0.01). There was a significant negative correlation between involuntary overtime and subjective well-being. Involuntary overtime might decrease the level of happiness (β = -0.187, p < 0.001), life satisfaction (β = -0.221, p < 0.001), and health status (β = -0.129, p < 0.05) and increase the depressive symptoms (β = 1.157, p < 0.05). While overtime had a minimal negative effect on individual subjective well-being, involuntary overtime significantly enlarged it. Improving individual's job autonomy is beneficial for individual subjective well-being.


Estimation of Young's modulus of pharmaceutical tablet obtained by terahertz time-delay measurement.
In this paper, it is suggested that Young's modulus of pharmaceutical tablets with different porosity can be estimated from terahertz (THz) pulse time delay. We demonstrate such a possibility using a training set of tablets compressed from starch acetate. Once the mechanical properties are taught to the THz measurement system, using an ideal tablet as a reference, it is possible to get information about the Young's modulus of the tablet. Here, we show that there are optical counterparts of classical mechanical laws that couple the Young's modulus and porosity of the tablet.


Analysis on the equity differential on household healthcare financing in developing countries: empirical evidence from Tanzania, East Africa.
Achieving equity in healthcare services has been a global priority. According to the literature, a slew of initiatives aimed at increasing household equity in healthcare financing have exacerbated the problem, making it hard for most developing countries to understand the real cause of the problem. The non-experimental research design has been used to explore the Tanzania Panel Survey (NPS) data 2019/2020, to investigate equity differential in household healthcare financing in Tanzania by the use of conventional instrumental variable methods of Two-stage and Three-stage least square methods RESULTS: Despite the global agenda of universal health coverage, this paper reveals that 86 percent of Tanzania lacks health insurance with a high degree of inequitable distribution of health facilities as 71.54 percent of the population is in rural areas, yet these areas have poor health systems compared to urban ones. These disparities increase pressure on household healthcare financing and widen the inequity and equality gaps simultaneously. Additionally, a household's income, education, health care waivers, out-of-pocket expenditure, and user fees have been found to have a significant impact on household equity in healthcare financing. To reverse the situation and increase equity in household healthcare financing in most developing countries, this paper suggests that an adequate pooling system should be used to allow more people to be covered by medical prepayment programs, and the donor-funded programs in developing countries should focus on health sector infrastructure development and not the capacity building.


Neonatal coxsackie B virus infection-a treatable disease?
Ten neonates with coxsackie B viral infection presented over a 3-month period. Clinical features included meningoencephalitis, thrombocytopenia, disseminated intravascular coagulopathy, cardiomyopathy, and hepatitis. Eight infants had multiorgan disease, four with severe myocardial dysfunction, of whom two died. All of the infants with severe disease developed symptoms within 7 days of age. In infants presenting within 10 days of birth, in all cases there were symptoms compatible with maternal infection prior to delivery. Severity was associated with perinatal transmission. Enteroviral polymerase chain reaction of CSF, urine, stool or throat swab was positive in nine of the ten babies. Seven of the infants were treated with a 7-day course of the new anti-picornaviral drug pleconaril (5 mg/kg 3 times daily). These cases highlight the importance of not missing coxsackie B viral infection in the differential diagnosis of the septic neonate, especially as there is now a potential treatment.


Magnetic nanoparticles for efficient cell transduction with Semliki Forest virus.
Semliki Forest virus (SFV) is a potential cancer gene therapy vector capable of providing high and transient expression of heterologous proteins in mammalian cells. However, SFV has shown suboptimal transduction levels in several cancer cell types as well as wide biodistribution of SFV has been observed after in vivo applications. Magnetic nanoparticles (MNPs) have been shown to increase cell transduction with several viral vectors in vitro under an external magnetic field and enhance magnetically guided viral vector delivery. Here, we examined a panel of MNPs for enhanced cancer cell transduction with SFV vector. Magneto-transduction using positively charged MNPs increased Semliki Forest virus transduction in TS/A mouse mammary carcinoma cells in vitro in the presence of fetal bovine serum. Positively charged MNPs efficiently captured SFV particles independently of capturing medium, and MNPs-SFV complexes were successfully separated from suspension by magnetic precipitation. These results reveal the potential application of MNPs for enhanced gene delivery by SFV vector as well as proposes magnetic precipitation for efficient concentration of SFV particles from different media.


Gut-associated cells of Derocheilocaris remanei (Crustacea, Mystacocarida).
The gut-associated cells (GA-cells) of the mystacocarid Derocheilocaris remanei were investigated by transmission electron microscopy. These cells are characterized by a dense cytoplasm, the presence of clear vesicles adjacent to the gut epithelium, glycogen, and lipid droplets. GA-cells envelop the midgut and hindgut and send blunt cytoplasmic extensions to the gut epithelium through its basal lamina. The GA-cells also extend dorsolateral projections to the body wall by means of intermediate cells. In addition to a mechanical function of suspending and stabilizing the gut, these cells may affect the flow of the hemocoelic fluid and may be implicated in the processes of transport, assimilation, and storage of nutrients.


Cardiovascular reactivity and proactive and reactive relational aggression among women with and without a history of sexual abuse.
This study examined the association between cardiovascular reactivity and proactive and reactive functions of relational aggression among women with and without a history of sexual abuse. Heart rate reactivity, blood pressure reactivity, and respiratory sinus arrhythmia reactivity while recounting a relational stressor (e.g., being left out) were assessed. Participants provided self-reports of relational aggression and a history of sexual abuse prior to age 16. Results indicated that cardiovascular reactivity was only associated with relational aggression among women with a history of sexual abuse. In addition, whereas blunted reactivity was associated with proactive relational aggression, exaggerated reactivity was associated with reactive relational aggression. These findings highlight the importance of considering contextual moderators of the association between cardiovascular reactivity and aggression; moreover, results highlight distinct cardiovascular correlates of different functions of aggression. Finally, the findings underscore the need for additional research examining the physiological correlates of aggressive behavior among women.


Enhanced anaerobic fermentation of waste activated sludge by reverse osmosis brine and composition distribution in fermentative liquid.
This study reported a "treating waste by waste" strategy to dispose waste activated sludge (WAS), i.e. reverse osmosis (RO) brine-enhanced anaerobic fermentation. RO brine was hazardous by-product from seawater desalination process, which contains numerous Na+. After 4-day RO brine-enhanced anaerobic fermentation at Na+ concentration of 0.33 mol/L, 5.0 g/L VSS reduction (37.9% of VSS) was achievable, leading to considerable soluble chemical oxygen demand (SCOD) release of 349.6 mg/g VSS. Acetic acid was predominant component in SCOD (31.1%), followed by propionic, butyric, valeric acids and proteins (14.0-17.6%). Sludge solubilization and SCOD composition in the enhanced anaerobic fermentation with RO brine and NaCl agent were similar, whereas less nutrient release and extracellular polymeric substance (EPS) disruption were achieved by RO brine, attributing to the Ca2+&Mg2+-caused skeleton strengthening on EPS matrix. Such RO brine-based strategy provided environmental and economic benefits, e.g. none chemical consumption, synchronous disposal of WAS and RO brine.


Effect of adjuvant interferon therapy on hepatitis B virus-related hepatocellular carcinoma: a systematic review.
The objective of this study is to evaluate the efficacy of adjuvant interferon therapy for hepatitis B virus-related hepatocellular carcinoma (HCC) after different previous therapy. An electronic search for articles about adjuvant treatment with IFN for patients with HCC published between 2000 and 2015 was conducted in MEDLINE, PubMed, Cochrane Library, and EMBASE databases. All data was tested with Stata12.0 software. Six trials with a total of 1054 subjects were screened according to inclusion and exclusion standards. Five hundred and seventeen HCC patients were treated with adjuvant treatment with IFN and 537 patients with placebo. Compared to the control group, both the recurrence rate and death rate of HCC in IFN group were statistically lower, especially after transhepatic arterial chemotherapy and embolization (TACE) treatment and both TACE and resection according to subgroup analysis. There is no statistical significance on the both recurrence and death rate of HBV-related hepatocellular carcinoma after surgical resection treatment (RR = 0.96, 95 % CI, 0.84 to 1.1, p = 0.59 for recurrence and RR = 0.78, 95 % CI, 0.60 to 1.04, p = 0.09 for death rates). Adjuvant IFN therapy may significantly reduced mortality as well as recurrence rate of patients with HBV-related HCC after no matter what the previous treatment. On the other hand, there is no statistical significance on the recurrence rate and mortality after surgical resection only. More research is needed into the relationship between effect of adjuvant interferon therapy and previous therapy, especially TACE.


Qatar population-specific centile charts of placental weight in 80 722 newborns: relation to maternal age, gestational age, newborn birth weight, and gender, between the 37 th and 42 nd weeks of gestation.
Data about placental weight (PW) in relation to birth weight (BW) and gestational age (GA) are lacking in Arabic countries. (a) to find out the national PW standards for babies born between 37th and 42nd weeks of gestation in male and female babies born in Qatar; (b) to study the relation, if any, between PW and maternal age, gestational age (GA), birth weight (BW), and gender of the newborn. A National population-based retrospective chart review study was conducted between 1-2016 to 12-2019 (n = 80 722). Data of gestational age (GA) at delivery (in weeks), newborn birth weight (BW), PW, and gender at birth, were collected from singleton babies born between 37 th and 42nd weeks of gestation. The PW ranged from 440 to 860 grams (g) with a mean of 682 ± 96 g. at term for boys and 673 ± 94 g. for girls. The mean BW was 3 036 ± 448 g and BW/PW ratio was 0.203 ± 0.026. The PW continued to increase through 41 weeks' gestation, in boys and girls with a significant decrease at the 42nd week of gestation. PW was significantly correlated with BW (r = 0.596, P: < 0.001) and GA (r = 0.15, P: <0.001) and accounted for 43.4% of the explained variability in birth weight. PW was a significant predictor of BW with a consistent increase in PW until the 41st week of gestation in boys and girls and a positive correlation with BW and GA.


Expression and network analysis of genes related to melanocyte development in the Silky Fowl and White Leghorn embryos.
Silky Fowl is a natural mutant with hyperpigmentation of various internal tissues. Although the mechanism of hyperpigmentation remains unclear, recent studies have shown that the abnormal migration of melanoblast and the absence of environmental barrier molecules are responsible for the hyperpigmentation in Silky Fowl. In this study, 13 genes related to melanocyte development were selected to detect expression changes between Silky Fowl and White Leghorn [including SRY-box 10 (Sox10), paired box (Pax3), stem cell factor (Scf), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit), endothelin type-B receptor (Ednrb), endothelin 3 (Edn3), microphthalmia-associated transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Trp1), tyrosinase-related protein-2 (Trp2), melanocortin-1 receptor (Mc1r), Agouti-related proteins (Agrp), and Proopiomelanocortin (Pomc)]. Transcript expression was detected in 11 stages from 2.5 to 15 days of incubation. In these embryonic periods, Mitf, Kit, Scf, and Agrp expressed earlier in Silky Fowl than in White Leghorn. Sox10, Ednrb, Kit, Mc1r, and Agrp, associating with the proliferation and differentiation of melanoblast, expressed higher (P < 0.05) in Silky Fowl than White Leghorn during 5-6 days of incubation. After day 8 of incubation, Mitf, Tyr, Trp1, Trp2, and Mc1r expressed higher (P < 0.05) in Silky Fowl than White Leghorn, while Agrp expressed higher (P < 0.05) in White Leghorn than Silky Fowl. Moreover, a regulatory network for melanocyte development was constructed based on the expression data. The network predicted novel regulatory relationships and confirmed relationships that have been reported. These results provide biological insight into the molecular mechanism of hyperpigmentation in the Silky Fowl. However, further investigation is needed to confirm these regulatory relationships.


Single-layer anastomosis in surgery of the large bowel. A prospective study on 316 cases in a university hospital.
A prospective study was undertaken to evaluate the results of a single layer appositional technique for large bowel anastomoses used in a University Hospital. 316 patients were entered during an 18-month period. Anastomoses were situated within the peritoneal cavity in 277 patients and below the peritoneal reflection in 39. No covering stoma was made. The incidence of clinical leakage was 1.6% and of wound infection 1.9%. These results compare favourably with those obtained by stapling. For intraperitoneal anastomoses and high anterior resection manual suture remains the standard technique and is less expensive than stapling. For low rectal tumours, there is still debate on the relative merits of stapling and various manual techniques of colo-anal anastomosis in terms of morbidity, tumour clearance and functional results.


Development of gold nanoparticles-based aptasensor for the colorimetric detection of organophosphorus pesticide phorate.
The present study reports a highly simple and rapid method for the detection of a widely used and extremely toxic organophosphorus pesticide, phorate. The detection employs a pesticide-specific aptamer as the recognition element and gold nanoparticles as the optical sensors. The aptamer, owing to its random coil structure, provides stability to the gold nanoparticles upon linking, thereby keeping the nanoparticles well dispersed. However, on the addition of the target pesticide, the aptamer acquires a rigid conformation resulting in the aggregation of the gold nanoparticles. Consequently, the color of the solution changes from red to blue and is easily observable with the naked eye. The proposed method was linear in the concentration range of 0.01 nM to 1.3 μm with the limit of detection as low as 0.01 nM. Moreover, the proposed assay selectively recognized phorate in the presence of other interfering substances and, thus, can be applied to real samples for the rapid and efficient screening of phorate.


Transfusion and blood donation on the screen.
In the 20th century, blood transfusion has become an indispensable therapy in carrying out and improving many medical and surgical applications. Its scope of influence goes well beyond that of medicine, because blood donation, an action with high social significance, is completely connected to progress in the field. The purpose of this research was to study, through films that show transfusion or blood donation, the impression that has been given to the public in the course of the 20th century and its sociologic impact. To accomplish this, we have used various sources from Histories of Cinema and from the Internet to identify films from different countries and from different epochs that touch on this theme. With these two components, the act of donation and the act of transfusion, the relatively short history of blood transfusion is distinguished by upheavals in both the medical and the sociopolitical fields of the past century. Movies, the most commonly shared cultural event and mirror of society, have simultaneously gone through their first century by showing the diversity of our feelings and the human condition. Through various cinematographic references, the authors offer an analysis of the use, by the Seventh Art, of values and illustrations that use blood donation and transfusion.


Relationship between plasma prolactin and the endocrine microenvironment of the developing human antral follicle.
The aim of the present study was to determine whether any obvious relationships exist between the circulating levels of prolactin at the time of ovariectomy and the endocrine microenvironment and developmental status of antral follicles. The concentrations of prolactin, follicle-stimulating hormone (FSH), and estradiol were measured in peripheral plasma and in antral fluid of follicles collected at varying stages of the menstrual cycle. In addition, the granulosa cells were recovered from each follicle (greater than or equal to 4 mm in diameter) and their numbers were quantitated. When the plasma levels of prolactin ranged from 11 to 100 ng/ml, the antral fluid levels of prolactin were uniformly low (less than 20 ng/ml) and the over-all level of intrafollicular activity remained unchanged. However, when the prolactin concentrations in plasma exceeded 100 ng/ml, the levels of prolactin in antral fluid were significantly elevated. Moreover, the high levels of intrafollicular prolactin were associated with a marked reduction in FSH accumulation and low levels of estradiol in antral fluid. Also, these follicles were severely deficient in granulosa cells. This marked reduction in intrafollicular activity was not associated with any significant changes in the mean levels of estradiol and FSH in peripheral plasma. These findings suggest that hyperprolactinemia is associated with a marked reduction in intraovarian activity and that the extent of this reduction may not be always apparent from the levels of circulating estradiol.


Integrating Ecosystem Health and Services for Assessing Ecological Risk and its Response to Typical Land-Use Patterns in the Eco-fragile Region, North China.
Changes in land-use patterns may increase the ecological risks faced by Eco-Fragile regions. It is vital for regional ecological restoration and management of Eco-Fragile regions to reasonably assess ecological risk and study its response to typical land-use patterns. Existing study on regional ecological risk largely ignored the internal representation of ecosystem health and ecosystem services to ecological risk, and also ignored the internal relationship between ecological risk and land use patterns. This study developed a regional ecological assessment model by describing the relationship between ecosystem health, ecosystem services and ecological risks. Among them, the ecosystem health assessment used the Net Primary Productivity, landscape index and ecosystem elasticity coefficient based on different land use patterns to build Vigor-Organization-Resilience (VOR) model, and the improved equivalent factor method was used to calculate the ecosystem service value. Taking the Fen River Basin (FRB), a typical Eco-Fragile region of the Loess Plateau, as a study region, spatial auto-correlation analysis was used to reveal the temporal and spatial changes and spatial clustering characteristics of regional ecological risk, and regression analysis was used to study the relationship between typical land use patterns and ecological risks, which was included in the consideration of ecological and environmental risk management strategies. The results show that the regions with high ecological risk are mainly distributed in the middle and southwest of the FRB; the regions with low ecological risk are mainly distributed in the north, east and west of the FRB. Both high-risk and low-risk areas show significant spatial clustering effects. The change of ecological risk in FRB is related to the land use patterns. The ecological risk is negatively related to the expansion of construction land and cultivated land at the county and patch scales. On this basis, the environmental management strategies at different scales are discussed. This study can helpful deepen the understanding of the impact of land use patterns on ecological risk, and can also provide important reference for regional ecological risk management and land use policies.


Reduction of Recombinant Adeno-Associated Virus Vector Adsorption on Solid Surfaces by Polyionic Hydrophilic Complex Coating.
Recombinant adeno-associated virus (rAAV) vectors have proven efficacy as gene therapy vehicles. However, non-specific adsorption of these vectors on solid surfaces is encountered during production, storage, and administration, as well as in quantification processes. Such adsorption has been reported to result in the loss of up to 90% of vector particles and can also result in high variability in vector genome quantification. In this study, we demonstrate the effective decrease of recombinant adeno-associated virus vector adsorption by application of a polyionic hydrophilic complex polymer coating on the surfaces of the tools used in viral vector quantification analyses [i.e., pipette tips, cryotube vials, and quantitative polymerase chain reaction (qPCR) plates]. qPCR analyses showed efficient recovery of vector particles from tools with this coating, with up to 95% of vector particle loss being prevented, leading to a higher transduction efficiency in vitro. Thus, the tested coating has the potential to be widely used in material processing in the gene therapy field.


[Analysis of platelet production following liver transplantation using the immature platelet fraction (IPF) parameter].
Although liver transplantation (LT) is frequently associated with thrombocytopenia, thrombopoiesis following LT remains to be evaluated. We analyzed platelet counts (PLT), immature Platelet Fraction (IPF), and thrombopoietin (TPO) in 8 patients with LT. PLT and IPF were measured using Sysmex XE-2100. TPO was measured with Human TPO ELISA Kit. In 7 of 8 patients with LT, IPF increased prior to the elevation of platelet counts. In 5 of 7 patients with increased IPF, TPO levels increased simultaneously with IPF, suggesting that IPF may reflect the production of platelets in patients with LT. IPF and TPO might be useful to monitor the platelet production in patients following LT.


Density-dependent size regulation and negative growth in the sea urchin Diadema antillarum Philippi.
This study documents size- and density-dependent growth (positive and negative), in the sea urchin Diadema antillarum. In the summer of 1983, an inverse relationship was found between Diadema test diameter and population density at seven sites in Lameshur Bay, St. John, United States Virgin Islands. The regression of this relationship improved when test diameter was plotted against density per unit grazing area. A field experiment demonstrated that 1) Diadema has the ability to reduce skeletal body size, and 2) direction (growth or shrinkage) and rate of growth can be predicted accurately based on the urchin's body size and population density. The ability to adjust body size as density fluctuates may allow Diadema to persist when density increases, by shrinking and reducing metabolic costs, and to take advantage of decreases in density, by increasing in size and fecundity.


Phage T4 lysozyme. Physical properties and reversible unfolding.
Phage T4 lysozyme has been used extensively in studies of the genetic code. However, little work has been done on the characterization of the purified enzyme. Therefore, we determined the spectral properties of native T4 lysozyme and used these properties to follow the unfolding transition. The ultraviolet absorption spectrum and solvent perturbation difference spectrum indicate that the aromatic amino acids are extensively exposed to solvent. The CD and ORD spectra are characteristic of a high fraction of helix. Guanidine hydrochloride denaturation results show that over a T4 lysozyme concentration range of 0.07-1 g/l the c-m equals 2.7 M guanidine hydrochloride at pH 5 and that the transition is 100% reversible as judged by enzymatic assay and four different spectrophotometric criteria: CD at 295 nm, CD at 223 nm, fluorescence intensity at 350 nm and wavelength of maximum fluorescence. Guanidine hydrochloride denaturation at pH 2.5 was followed using fluorescence emission and has a c-m equals 1.7 M guanidine hydrochloride, indicating a strong pH dependence of chemical unfolding. Reversible thermal denaturation conditions were located at acid pH, 0.2 M NaCl, 10-4 M dithiothreitol and 10-6 M T4 lysozyme. The CD signal at 223 nm was used to measure the unfolding. Thermodynamic analysis of the thermal data showed an increase in T-m, increment H-unf and increment S-unf with increasing pH.


Different flexibility of the upstream regulatory regions of two differently expressed pea rbcS genes studied by theoretical evaluation of DNA distortion energy and cyclization kinetics.
Different superstructural features of the upstream regulatory regions of the two pea genes rbcS-3A and rbcS-E9 have been derived using a theoretical method, developed in our laboratory a few years ago, which evaluates the DNA distortion energy from a matrix of the deviations of the 16 possible dinucleotides from the standard B conformation. The theoretical analysis, which predicts different flexibilities of the regulatory regions of the two genes, is in satisfactorily good agreement with experimental evaluations from gel electrophoretic mobility and cyclization kinetics, suggesting a possible model to explain the largely different transcription efficiencies of the two genes.


Live-cell imaging of microtubules and microtubule-associated proteins in Arabidopsis thaliana.
Microtubules and microtubule-associated proteins (MAPs) play fundamental roles in plant growth and morphogenesis. The ability to observe microtubules and MAPs in living cells using fluorescent protein fusions has propelled plant scientists forward and given them the opportunity to answer longstanding biological questions. In combination with the genetic resources available in the model plant Arabidopsis thaliana, our mechanistic understanding of how the microtubule cytoskeleton affects plant life has dramatically increased. It is a simple process to construct transgenic A. thaliana plants that express fluorescent protein fusions by using the disarmed plant pathogen Agrobacterium tumefaciens. Several screening steps are necessary to ensure that the fusion protein accurately mimics the native protein because transgenes are inserted randomly into the A. thaliana genome. To image the fluorescent proteins in planta, confocal microscopy is used to alleviate issues caused by specimen thickness and autofluorescence.


The spatial arrangement of the semicircular canals of the pigeon.
The spatial orientation of the semicircular canals (SCC) was measured in the pigeon by fitting the best plane over 10 to 15 stereotaxically determined points to each canal. The vectors defining each canal plane are presented in the standard stereotaxic position and for free moving behavior, and the coplanarity or orthogonality of pairs of semicircular canals are discussed.


Infection patterns in cyclosporine-treated cadaveric renal transplant patients.
Immunosuppression with Cs regimens has not significantly altered infection patterns relative to earlier modalities. However, reports of increased infection, especially with CMV/PCC, are not borne out in our experience both in numbers and timing of infections. Patients on low-dose Cs immunosuppression do continue to acquire infectious complications but, in general, rarely will lose their grafts or lives.


Critical dosages for oral contraceptives.
An investigation was carried out into the effectiveness of Ovostat E, a low dosage oral contraceptive. One hundred women, aged between 17 and 39 years, participated in the trial; 47 women completed 12 treatment cycles and 42 of these completed all 24 treatment cycles. The following results were obtained by computer analysis: Reliability was 100% and the Pearl Index therefore = 0; Cycle Control; length: an obvious regulating effect; 85-3% was the average percentage of women with a cycle length of 26 to 30 days; withdrawal bleeding occurred in 94-6% of cycles; duration of withdrawal bleeding: no change in 26-0%; 1--2 days shorter in 51-7%; 1--2 days longer in 5-6%; intensity of withdrawal bleeding: no change in 61-9%; decreased in 29-3%; increased in 3-4%; irregular bleedings occurred in 4-6% of cycles. The most common complaints were nervousness, headache and nausea, the last two virtually disappearing after the 3rd treatment cycle. Of the 49 women who continued the investigation for the further eighteen months, 2 dropped out because of intolerance, 1 because of objections to the periodic check-ups and 1 for reasons unknown.


Eliminating the original cargos of glioblastoma cell-derived small extracellular vesicles for efficient drug delivery to glioblastoma with improved biosafety.
Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded proteins or RNAs) from parent cancer cells in tumor progression severely hinder the practical application. In this study, a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore, doxorubicin (DOX) transported by the saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.


The retinal renin-angiotensin system: roles of angiotensin II and aldosterone.
In the present review we examine the experimental and clinical evidence for the presence of a local renin-angiotensin system within the retina. Interest in a pathogenic role for the renin-angiotensin system in retinal disease originally stemmed from observations that components of the pathway were elevated in retina during the development of certain retinal pathologies. Since then, our knowledge about the contribution of the RAS to retinal disease has greatly expanded. We discuss the known functions of the renin-angiotensin system in retinopathy of prematurity and diabetic retinopathy. This includes the promotion of retinal neovascularization, inflammation, oxidative stress and neuronal and glial dysfunction. The contribution of specific components of the renin-angiotensin system is evaluated with a particular focus on angiotensin II and aldosterone and their cognate receptors. The therapeutic utility of inhibiting key components of the renin-angiotensin system is complex, but may hold promise for the prevention and improvement of vision threatening diseases.


A basic fibroblast growth factor improved the quality of skin grafting in burn patients.
To avoid hypertrophic scars in burn wounds, the simultaneous application of basic fibroblast growth factor (bFGF) with regular surgical debridement and skin grafting was investigated for skin hardness by clinical examination and instrumental measurement. As little is known about the role of bFGF in wounds, burn wound scars were tested for hardness. Burn scars in various anatomical locations at least 1 year after final wound healing clinically demonstrated a significantly lower hard score in bFGF-treated wounds than in non-bFGF wounds (0.95+/-0.51 versus 2.3+/-0.66, respectively, p<0.01). In addition, a durometer, which is widely used in industry to measure materials similar to skin, such as rubber and thread-balls, demonstrated a significantly lower reading in bFGF-treated wounds than in non-bFGF wounds (7.9+/-3.64 versus 15.5+/-4.39, bFGF versus non-bFGF, respectively, p<0.01). The results demonstrated that burn wounds treated with clinically approved bFGF might contribute to a better cutaneous wound quality, at least in terms of hardness.


Biology of mesenchymal stem cells.
Mesenchymal stem cells are present in many human tissues and serve as a readily available source of undifferentiated cells being capable to form specific tissues like bone, cartilage, fat, muscle and tendon. They represent an attractive and promising field in tissue regeneration and engineering for treatment applications in a wide range of trauma and orthopaedic conditions. This article covers the most important aspects of recent research data demonstrating the combination of physiological properties of mesenchymal stem cells (MSCs) and applications in the clinical setting.


The non-obstructive ectopic ureterocele.
We have seen 5 children with a non-obstructive ectopic ureterocele associated with an undilated upper pole collecting system. Thus the telltale signs of renal duplication found with obstruction of the upper pole were absent. Cystoscopy confirmed the diagnosis when retrograde injection of the ureterocele outlined a narrow ureter and small dysplastic kidney. Because reflux usually was present in the ipsilateral lower pole ureter (86 per cent) surgical treatment consisted of excision of the ureterocele and common sheath ureteral reimplantation. Removal of the small non-functioning upper renal segment was not necessary in most instances. The embryology of this anomaly is discussed.


A simple clinical score to identify likely hepatitis B vaccination non-responders - data from a retrospective single center study.
About 10% of Hepatitis B vaccinated individuals mount no protective antibody levels against the hepatitis B surface antigen (HBs-Ag). Older age at primary immunization, obesity and smoking have previously been reported as risk factors associated with vaccine non-response. Here we tested whether these factors alone may allow selecting subjects that benefit from individualized immunization schedules. Retrospective database analysis screening > 15,000 individual anti-HBs-IgG measurements. Non-responders (NR; anti-HBs-IgG < 10 IU/L) and low-responders (LR; anti-HBs-IgG 10-100 IU/L) were identified. Vaccine type, demographics, lifestyle, and immunological factors (leucocyte subset counts) were compared between NR, LR, and responders (R). We identified 113 LR/NR and compared them to 134 vaccine responders. We confirmed higher median age at primary vaccination (24.0 (R) vs. 30.5 (NR) vs. 31 (LR) years, p = 0.001), higher median BMI (23.2 kg/m2 (R) vs. 23.4 kg/m2 (NR) vs. 25.1 kg/m2 (LR), p = 0.001) and being a smoker (% smokers: 30.8% (R) vs. 57.1% (NR) vs. 52.5% (LR), p = 0.01) as factors negatively associated with anti-HBs-IgG levels. In a ROC analysis including these factors in a 6-point score, a high score predicted non-response with a specificity of 85% but at low sensitivity (47%). A simple clinical risk score based on age, obesity, and smoking identifies individuals with a high likelihood of vaccine failure. Non-responders with a low score are candidates for in-depth analyses to better understand the immunological causes of HBV vaccine non-response.


Probable transmission of HIV from an orthopedic surgeon to a patient in France.
Transmission of HIV from infected health care workers to patients has been documented in only one cluster involving 6 patients of a dentist in Florida. In October 1995, the French Ministry of Health offered HIV testing to patients who had been operated on by an orthopedic surgeon in whom AIDS was recently diagnosed. To determine whether the surgeon transmitted HIV to patients during operations. Epidemiologic investigation. The practice of an orthopedic surgeon in a French public hospital. 1 surgeon and 983 of his former patients. 3004 patients who had undergone invasive procedures were contacted by mail for counseling and HIV testing. One HIV-positive patient was interviewed, and DNA sequence analysis was performed to compare the genetic relation of the patient's and the surgeon's viruses. Infection-control precautions and the surgeon's practices were assessed. Of 983 patients in whom serologic status was ascertained, 982 were HIV negative and 1 was HIV positive. The HIV-positive patient, a woman born in 1925, tested negative for HIV before placement of a total hip prosthesis with bone graft (a prolonged operation) performed by the surgeon in 1992. She had no identified risk for HIV exposure. Molecular analysis indicated that the viral sequences obtained from the surgeon and the HIV-infected woman were closely related. Infection-control precautions were in accordance with recommendations, but blood contact between the surgeon and his patients occurred commonly during surgical procedures. An HIV-infected surgeon may have transmitted HIV to one of his patients during surgery.


Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies.
In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing. Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.


[Synthesis of O-(beta-diethylaminoethyl)cinchoninaldoxime with local anesthetic activity].
The synthesis and the pharmacological evaluation of a new series of O-(beta-diethylaminoethyl)aldoxines derived from cinchonine-aldehydes substituted at position 2 by alkyl and alkoxyl groups are described.


A novel selective-excitation RF pulse for magnetic resonance imaging.
A selective-excitation radiofrequency (RF) pulse that uses hard pulses composed of a sequence of composite pulses with positive and negative phases (P/N pulse) is proposed herein. Because the amplitude of the RF signal is unchanged during the excitation, RF amplification can be accomplished using a nonlinear RF power amplifier (i.e., class C or D type). In this article, Fourier series have been first used to analyze the equivalence between the proposed P/N pulse and the conventional soft pulse on selective excitation. Subsequently, computer simulations based on density-matrix theory are used to compare the excitation profiles of both the soft and the P/N pulses. The excitation profiles of the P/N pulses have been measured experimentally through a home-built 0.3-T magnetic resonance imaging (MRI) system. In addition, several slices of images have been obtained as proofs by using the multislice two-dimensional spin echo sequence through replacement of the conventional soft pulse by the proposed P/N pulse. Because the perfect selectivity of the proposed P/N pulse, it can be used for imaging studies to improve the efficiency of amplification at the lowest cost.


Neural mechanisms of the reflex inhibition and excitation of gastric motility elicited by acupuncture-like stimulation in anesthetized rats.
The effects of acupuncture-like stimulation of the various segmental areas on gastric motility were examined in anesthetized rats. An acupuncture needle (diameter 340 microns) was inserted into the skin and underlying muscles at a depth of 4-5 mm and was twisted right and left once every second for 60 s. Gastric motility in the pyloric region was measured with the balloon method. Gastric motility was inhibited by acupuncture-like stimulation applied to the abdomen and lower chest region, and was often excited when the limbs were stimulated, in all cases in which stimuli were delivered to the skin and muscles, the skin alone, and the underlying muscles alone. The inhibitory gastric response to abdominal stimulation was accompanied by an increase in the activity of the gastric sympathetic efferent nerve and was abolished by severance of either the sympathetic nerve branches to the stomach or the lower thoracic spinal nerves. The abdominal stimulation enhanced the activity of the lower thoracic spinal afferent nerves. The excitatory gastric response to hindpaw stimulation was accompanied by an increase in the activity of the gastric vagal efferent nerve and was abolished by severance of either the bilateral vagi or the femoral and sciatic nerves. The hindpaw stimulation enhanced the activity of the femoral and sciatic afferent nerves. In the spinalized animals, the inhibitory gastric response elicited by abdominal stimulation was present, and the hindpaw stimulation did not produce any gastric response. We conclude that the inhibitory gastric response elicited by acupuncture-like stimulation of the abdomen is a reflex response. Its afferent nerve pathway is composed of abdominal cutaneous and muscle afferent nerves, the efferent nerve pathway is the gastric sympathetic nerve, and its reflex center is within the spinal cord. The excitatory gastric response elicited by acupuncture-like stimulation of a hindpaw is also a reflex response. Its afferent nerve pathway is composed of hindpaw cutaneous and muscle afferent nerves, the efferent nerve pathway is the gastric vagal efferent nerve, and its reflex center requires the presence of the brain. Furthermore, the excitatory and the inhibitory gastric reflex responses were not influenced by i.v. administration of naloxone (0.4-4 mg/kg), suggesting that endogenous opioids are not involved in the present reflexes.


Serum pregnancy-associated plasma protein a in patients with heart failure.
Pregnancy-associated plasma protein A (PAPP-A) proteolyzes insulin-like growth factor (IGF)-binding proteins and thus increases IGF-1 bioactivity. PAPP-A has been reported to be involved in various pathophysiologic abnormalities; however, the clinical significance of PAPP-A has not been examined in cases of heart failure (HF). We hypothesized that PAPP-A levels might be correlated with the severity of HF. PAPP-A and B-type natriuretic peptide (BNP) levels were measured in 262 subjects (182 HF patients and 80 control subjects). PAPP-A levels were higher in patients with HF than in control subjects and increased with advancing New York Heart Association functional class. There were 53 cardiac events during a mean follow-up period of 796 days. PAPP-A levels were higher in patients with cardiac events than in event-free patients. Patients were divided into 3 groups on the basis of their PAPP-A and BNP levels. Kaplan-Meier analysis demonstrated that the group with both high BNP with high PAPP-A had a significantly higher cardiac event rate than other groups. Serum PAPP-A levels were related to the severity of HF and associated with a high risk for adverse cardiac events in HF patients, suggesting that PAPP-A might be involved in the pathogenesis of HF.


Development of experimental and theoretical crystal lattice organic photochemistry: the quantitative cavity. Mechanistic and exploratory organic photochemistry.
The photochemistry of organic reactants in the crystalline state has a long history. What has been lacking is comprehensive theory defining what controls the course of these reactions which quite often afford products not obtainable in solution. Also lacking has been solid-state rearrangement chemistry with accompanying theory. In our research over the past two decades we have developed theoretical treatments of solid-state reactivity. This report describes the development of this research from its primitive beginnings to the present.


Sensitivity to tri-o-cresylphosphate neurotoxicity on n-hexane exposed hens as a model of simultaneous hexacarbon solvent and organophosphorus occupational intoxication.
Hens were given a single oral dose (0.235 mg/kg) of tri-o-cresylphosphate (TOCP) during chronic n-hexane treatment (200 mg/kg daily, 5 days/week). They were compared with other animals treated only with n-hexane or only with TOCP. Animals treated with a higher TOCP dose (1 ml/kg) were used as positive controls. The animals treated with both n-hexane and TOCP showed rapid development of severe ataxia. The rate of the ataxia development was similar to that of the positive controls but with earlier onset of the first signs and with less loss of body weight. However, animals treated only with n-hexane, under the same conditions, showed only reversible weakness and sedative effects, and those treated only with TOCP showed slow and slight ataxia development. The n-hexane- and TOCP-treated hens showed axonal swelling with myelin retraction associated with Ranvier's nodes, which is characteristic of long hexacarbon exposure. Some internodal swellings were also observed but less frequently than the paranodal swellings. The time course of the ataxia development was similar to an organophosphorus-induced delayed neuropathy (OPIDN); however, the light microscopy observation more closely resembled hexacarbon neuropathy. The results suggest a potentiation effect of n-hexane and TOCP neurotoxicities which could be related to some human occupational neuropathies.


Proliferation assessment in breast carcinomas using digital image analysis based on virtual Ki67/cytokeratin double staining.
Manual estimation of Ki67 Proliferation Index (PI) in breast carcinoma classification is labor intensive and prone to intra- and interobserver variation. Standard Digital Image Analysis (DIA) has limitations due to issues with tumor cell identification. Recently, a computer algorithm, DIA based on Virtual Double Staining (VDS), segmenting Ki67-positive and -negative tumor cells using digitally fused parallel cytokeratin (CK) and Ki67-stained slides has been introduced. In this study, we compare VDS with manual stereological counting of Ki67-positive and -negative cells and examine the impact of the physical distance of the parallel slides on the alignment of slides. TMAs, containing 140 cores of consecutively obtained breast carcinomas, were stained for CK and Ki67 using optimized staining protocols. By means of stereological principles, Ki67-positive and -negative cell profiles were counted in sampled areas and used for the estimation of PIs of the whole tissue core. The VDS principle was applied to both the same sampled areas and the whole tissue core. Additionally, five neighboring slides were stained for CK in order to examine the alignment algorithm. Correlation between manual counting and VDS in both sampled areas and whole core was almost perfect (correlation coefficients above 0.97). Bland-Altman plots did not reveal any skewness in any data ranges. There was a good agreement in alignment (>85 %) in neighboring slides, whereas agreement decreased in non-neighboring slides. VDS gave similar results compared with manual counting using stereological principles. Introduction of this method in clinical and research practice may improve accuracy and reproducibility of Ki67 PI.


Differences in range of motion with the same combined anteversion after total hip arthroplasty.
We investigated the various impingement angles (including both bony and prosthetic impingement) and impingement types that can occur after THA, even when the same combined anteversion parameter is used. We also investigated the relationship between impingement angle and acetabular morphology or femoral anteversion. We evaluated 83 patients with no hip arthritis. We divided them into six groups according to acetabular CE angle (≤15°, >15-≤25°, and >25°) and femoral anteversion (≤20° and >20°). Using three-dimensional templating software, we changed stem and cup anteversion to satisfy a combined anteversion (CA) of 50° in each hip (stem anteversion + cup anteversion = 50°) and investigated the resulting impingement angles. Even with the same CA, differences in impingement angle occurred: 18.3° ± 7.2° with flexion, 30.2° ± 9.7° with internal rotation at 90° flexion, 20.2° ± 12.5° with extension, and 26.2° ± 7.8° with external rotation. As stem anteversion increased, the impingement type changed from prosthetic impingement to bony impingement in flexion and internal rotation and from bony impingement to prosthetic impingement in extension and external rotation. The flexion angle and internal rotation angle at 90° flexion increased (p < 0.016) as CE angle decreased. There were no significant differences between high and low femoral anteversion. Combined anteversion theory should be used with care because of large differences in impingement angles. A stem anteversion of 30° and cup anteversion of 20° appear to be ideal for obtaining a larger impingement angle under this condition.


Primary afferent projections to the sacral secondary visceral gray: a quantitative electron microscopic examination in the cat.
Afferent input to the sacral secondary visceral gray matter was studied by quantitatively assessing synaptic degeneration that follows ipsilateral sacral dorsal rhizotomy. Five days after the lesions, slightly more than 25% of the synaptic contacts showed degenerative changes. The majority of the reactive synapses contained clear spherical vesicles (S type). Boutons containing dense core vesicles (GS type) also showed degenerative changes, and together with S boutons constituted more than 96% of the reactive terminals. Degenerating S type synapses were found only on dendrites whereas GS boutons were observed on both cell bodies and dendrites. Further examination revealed that although there were more S than GS synapses in the nucleus, the percentage of GS terminals affected was greater than that for S type boutons. These results demonstrate a direct primary afferent input to the sacral secondary visceral gray matter utilizing chiefly two different synaptic types.


Therapeutic vaccination with papillomavirus E6 and E7 long peptides results in the control of both established virus-induced lesions and latently infected sites in a pre-clinical cottontail rabbit papillomavirus model.
This study was performed to test the therapeutic efficacy of overlapping long E6 and E7 peptides, containing both CD4+ T-helper and CD8+ CTL epitopes, on CRPV-induced lesions, which is an appropriate pre-clinical model for HPV diseases, including recurrent respiratory papillomatosis (RRP). Therapeutic peptide vaccination was able to significantly control wart growth (p < 0.01) and abrogate latent CRPV infection (p = 0.0006) compared to controls. Vaccination was associated with a T(H)1 T cell response, as suggested by a strong DTH skin test, antigen-specific proliferation of PBMC and a minimal IgG antibody response. Thus, this study shows promise for treatment of RRP by vaccination with long peptides.


Cross-modal attentional effects of rhythmic sensory stimulation.
Temporal regularities are ubiquitous in our environment. The theory of entrainment posits that the brain can utilize these regularities by synchronizing neural activity with external events, thereby, aligning moments of high neural excitability with expected upcoming stimuli and facilitating perception. Despite numerous accounts reporting entrainment of behavioural and electrophysiological measures, evidence regarding this phenomenon remains mixed, with several recent studies having failed to provide confirmatory evidence. Notably, it is currently unclear whether and for how long the effects of entrainment can persist beyond their initiating stimulus, and whether they remain restricted to the stimulated sensory modality or can cross over to other modalities. Here, we set out to answer these questions by presenting participants with either visual or auditory rhythmic sensory stimulation, followed by a visual or auditory target at six possible time points, either in-phase or out-of-phase relative to the initial stimulus train. Unexpectedly, but in line with several recent studies, we observed no evidence for cyclic fluctuations in performance, despite our design being highly similar to those used in previous demonstrations of sensory entrainment. However, our data revealed a temporally less specific attentional effect, via cross-modally facilitated performance following auditory compared with visual rhythmic stimulation. In addition to a potentially higher salience of auditory rhythms, this could indicate an effect on oscillatory 3-Hz amplitude, resulting in facilitated cognitive control and attention. In summary, our study further challenges the generality of periodic behavioural modulation associated with sensory entrainment, while demonstrating a modality-independent attention effect following auditory rhythmic stimulation.


A phase I study to determine the effect of tamoxifen on the pharmacokinetics of a single 250 mg oral dose of gefitinib (IRESSA) in healthy male volunteers.
To determine the effect of tamoxifen on the pharmacokinetics of a single 250 mg oral dose of gefitinib (IRESSA) in healthy volunteers. An open-label, single-center, phase I study in healthy male volunteers. Each volunteer received a single 250 mg oral dose of gefitinib on day 1. On days 11-14, oral loading doses of 60 mg tamoxifen were administered, followed by 20 mg tamoxifen for a further 16 days to maintain steady-state exposure. On day 24, volunteers received a second single 250 mg oral dose of gefitinib. The last dose of tamoxifen was given on day 30. Pharmacokinetic and safety assessments were conducted throughout the trial. A total of 18 volunteers were recruited. The presence of tamoxifen did not have a clinically significant effect on the primary variables AUC and Cmax of gefitinib, nor on the secondary variables AUC(0-t), tmax, t1/2, and lambdaz. The geometric least square mean values for AUC were 3,407.6 versus 3,397.9 ng.h/ml in the absence and presence of tamoxifen, respectively (90% CL 0.894, 1.112) and for Cmax were 110.8 versus 103.6 ng/ml, respectively (90% CL 0.786, 1.111). The combination of gefitinib with tamoxifen was generally well tolerated by the volunteers. There were no serious adverse events and no volunteer discontinued the study due to an adverse event. NCI-CTC grade 1/2 drug-related adverse events were observed in seven volunteers, including loose stools and skin events associated with gefitinib, and lethargy and headache, flushing, and dizziness associated with tamoxifen. This study suggests that tamoxifen has no significant effect on the pharmacokinetics, tolerability, or safety of a single 250 mg oral dose of gefitinib. Therefore, in clinical investigations of this combination, no dose adjustment of gefitinib is indicated.


High-performance flexible organic field effect transistors with print-based nanowires.
Polymer nanowire (NW) organic field-effect transistors (OFETs) integrated on highly aligned large-area flexible substrates are candidate structures for the development of high-performance flexible electronics. This work presents a universal technique, coaxial focused electrohydrodynamic jet (CFEJ) printing technology, to fabricate highly aligned 90-nm-diameter polymer arrays. This method allows for the preparation of uniformly shaped and precisely positioned nanowires directly on flexible substrates without transfer, thus ensuring their electrical properties. Using indacenodithiophene-co-benzothiadiazole (IDT-BT) and poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8-BT) as example materials, 5 cm2 arrays were prepared with only minute size variations, which is extremely difficult to do using previously reported methods. According to 2D-GIXRD analysis, the molecules inside the nanowires mainly adopted face-on π-stacking crystallite arrangements. This is quite different from the mixed arrangement of thin films. Nanowire-based OFETs exhibited a high average hole mobility of 1.1 cm2 V-1 s-1 and good device uniformity, indicating the applicability of CFEJ printing as a potential batch manufacturing and integration process for high-performance, scalable polymer nanowire-based OFET circuits. This technique can be used to fabricate various polymer arrays, enabling the use of organic polymer semiconductors in large-area, high-performance electronic devices and providing a new path for the fabrication of flexible displays and wearable electronics in the future.


[Pharmacological effect of exogenous histones on muscles].
Different histone fractions contain sequences homologous to those of several regulatory peptides. All the histone fractions demonstrated dose-dependent positive chronotropic effect in spontaneously contracting rat atrial preparations. The range of their activity was as follows: H4 greater than H1 greater than H2a much greater than H3. Synthetic COOH-terminal histone H4 pentapeptide (historphin) Tyr-Gly-Phe-Gly-Gly demonstrated opioid activity by inhibiting electrostimulated guinea-pig ileal contractions. It is suggested that some biological activities of histones are related to the presence of regulatory peptide sequences in their structure.


Habitual pattern of food intake in patients with liver disease.
Patients with liver disease are frequently undernourished. We determined the habitual pattern of energy intake and intake of protein, fat, carbohydrate and alcohol in patients with liver disease. 20 Patients differing with respect to cause, duration and severity of liver disease reported their habitual food intake using a 7-day food record. Control subjects formed a representative sample of the Dutch population. The results showed that patients with liver disease, had a significantly decreased daily energy intake (both expressed in absolute values and per kg body mass), compared with control subjects. Total fat intake was reduced in patients, whereas total intake of protein, carbohydrate and alcohol was similar to the control group. In the first 4 hours after rising, energy and protein intake were significantly increased in the patient group. During the evening the consumption of protein was lower in patients with liver disease than in control subjects. These findings are probably functional in order to minimize episodes of catabolism.


Dinitrofluorobenzene-induced rigor in ileal longitudinal smooth muscle of the guinea-pig.
1. The administration of 2,4-dinitrofluorobenzene (DFB) (0.1-1 mM) to the ileal longitudinal muscle produced contractions within seconds of its administration. 2. A component of the first 2 min duration of the phasic phase of 1 or 0.5 mM DFB contraction and the first phase of 0.35 or 0.1 mM DFB contraction was inhibited by Ca2+ antagonists, 1 x 10(-6) M D-600. 3. The DFB contraction resistant to D-600 began to develop when the tissue ATP concentration rapidly reduced. 4. The DFB contraction in ileum consists of two components; an initial fast contraction which is sensitive to Ca2+ antagonists, and a late contraction referred to as a rigor which is resistant to it.


Cholecystokinin-like immunoreactivity in cat extra-adrenal paraganglia.
In the cat peripheral dopaminergic organs such as the carotid body, subclavian bodies, aortico-pulmonary glomera and small intensively fluorescent cell (SIF cell) clusters of the superior cervical ganglion and the nodose ganglion were found to contain cholecystokinin (CCK)-immunoreactive paraganglionic cells. Thus, the extra-adrenal paraganglionic system may serve as a model for studying peripheral interactions of CCKergic and dopaminergic mechanisms.


Factors associated with fatal coronavirus disease 2019 infections among cancer patients in the US FDA Adverse Event Reporting System database.
Aim: To explore factors affecting coronavirus disease 2019 (COVID-19) mortality among cancer patients based on a pharmacovigilance database. Methods: US FDA Adverse Event Reporting System (FAERS) quarterly data extract files were reviewed for quarters two, three and four of 2020 (i.e., April to December). Patients with an indication related to malignancy and a reported COVID-related reaction were selected. Multivariate logistic regression analysis for factors associated with a fatal outcome was conducted. Results: A total of 2708 patients were included. The following factors were associated with fatal COVID-19 infection: older age (odds ratio [OR]: 1.03; 95% CI: 1.01-1.04), male sex (OR: 1.43; 95% CI: 1.07-1.91), non-US report source (OR: 2.46; 95% CI: 1.93-3.13), hematological malignancy (OR: 1.62; 95% CI: 1.28-2.07), potentially immunosuppressive treatment (OR: 1.83; 95% CI: 1.30-2.58) and diagnosis in quarter two versus quarter four (OR: 1.62; 95% CI: 1.27-2.07). Conclusion: Within FAERS reports, cancer patients who are older, males and receiving immunosuppressive treatment and those with hematological malignancies were at a higher risk of death because of COVID-19 infection.


[Falsely elevated-bispectral index].
We report a case of a falsely elevated-bispectral index (BIS) during a general anaesthesia combining remifentanil TCI, desflurane and nitrous oxide for an isolated-limb chemotherapy. During surgery, BIS increased and stabilized around 70, with neither residual neuromuscular blockade nor clinical sign of awareness. These high BIS values were attributed to high-electromyographic activity and electric artefacts, such as extracorporeal-circulation machine and tourniquet. At the end of the surgery, the BIS returned to expected values around 50. The patient did not complain of intraoperative recall. This case reminds us that the BIS has some limits as being sensitive to EMG or environment artefacts that should be eliminated before deepening anesthesia. To do so, a decision algorithm is proposed that may be used for all situations of surprising high BIS, taking into account the level of neuromuscular blockade, clinical response to orders and the presence of devices likely to induce electrical or mechanical artefacts.


Facial Nerve Stimulation as a Complication of Cochlear Implantation.
Facial nerve stimulation (FNS) can be considered as one of potential complications of the cochlear implant (CI) procedure. A number of conditions have been identified that appear to predispose patients to facial nerve stimulation. Facial nerve stimulation can frequently be resolved with minimal changes in speech processor fitting but this may lead to reduction in the outcome. To overcome the aberrant FNS after cochlear implantation with preservation of patient performance. A retrospective review has been made of the clinical features of 2 patients out of 175 children younger than 17 years of age consecutively implanted, from April 2014 to December 2017 (in the ENT Department at the National Hearing and Speech Institute, Egypt). These 2 patients developed post-implantation facial nerve stimulation. Changing the programming strategies help to overcome this complication. FNS is one of the most frequent complications of the CI procedure. It can produce significant discomfort, in some cases may lead to limiting the use of an implant. So, preoperative counseling of the patient and surgical planning, is essential to avoid such complication. The management of FNS requires awareness with programming techniques and, in some cases, surgical explantation or re-implantation.


Olfactory discrimination in the western lowland gorilla, Gorilla gorilla gorilla.
The olfactory abilities of great apes have been subject to little empirical investigation, save for a few observational reports. This study, using an habituation/dishabituation task, provides experimental evidence for a core olfactory ability, namely, olfactory discrimination, in the gorilla. In Experiment 1, six zoo-housed western lowland gorillas were individually presented with the same odour on four trials, and with a novel odour on the fifth trial. Odours (almond and vanilla) were presented on plastic balls, and behavioural responses of sniffing and chewing/licking the balls were recorded. A second experiment presented the same odour on four trials and no odour on the fifth to examine whether any dishabituation was due to the presence of a new odour or the absence of the familiar odour. Gorillas habituated their behaviour with repeated presentation of the same odour, but dishabituated, i.e. increased sniffing and chewing/licking, when presented with the novel odour. No dishabituation was noted when using water as the stimulus across all trials or when used as the novel odour. Overall, results show that gorillas are able to discriminate between odours.


Exposure to bisphenol A induced oxidative stress, cell death and impaired epithelial homeostasis in the adult Drosophila melanogaster midgut.
Recently, the chemical compound Bisphenol A (BPA) has been attracting worldwide attention due to its various toxic effects in animals, including reprotoxicity, neurotoxicity, hepatoxicity, and nephrotoxicity. Here, the midgut of adult Drosophila melanogaster (D. melanogaster), an invertebrate model organism, was employed to investigate the gastrointestinal toxicity of BPA in D. melanogaster and explore its underlying mechanisms of action in insects. As a result, exposure of flies to 0.5 mM BPA resulted in a dramatic morphological alteration of D. melanogaster midgut and decrease in survival rates and climbing ability of flies. Further study indicated that BPA induced high levels of oxidative stress in D. melanogaster midgut due to the imbalance between the production of reactive oxygen species and the activities of cellular antioxidant enzymes, including glutathione-S-transferase, catalase and superoxide dismutase. Oxidative stress induced by BPA then caused intestinal epithelial cell death and gut barrier dysfunction and elevated gut permeability, leading to oxidative injury of midgut epithelium. Antioxidant vitamin E alleviated midgut injury induced by BPA. Subsequently, BPA-induced oxidative injury of midgut further stimulated the proliferation of intestinal stem cell (ISC) and ISC-mediated midgut regeneration, but did not alter cell fate determination of ISCs in Drosophila midgut. Meanwhile, activation of Jun N-terminal kinase signal pathway was found to be required for BPA-induced cell death and tissue regeneration in midgut. Collectively, the present study provided additional evidence from an invertebrate model organism that BPA exposure induced gastrointestinal toxicity in D. melanogaster and further extended our understanding of the molecular mechanisms mediating BPA toxicity in insects.


Failure to intensify hypertension therapy after rejected aliskiren claims.
Failure to intensify therapy when indicated is a serious problem in the management of hypertension. Patients having an antihypertensive prescription rejected because of utilization management tools may be at a high risk of failing to intensify their therapy when it is warranted. The goal of this study was to investigate the patterns of therapy change after rejected aliskiren claims because of utilization management tools such as prior authorization, step therapy, and restrictive formulary. A retrospective study was conducted using data from a large national pharmacy benefits manager. Patients with a rejected aliskiren claim because of utilization management and who were naive to aliskiren treatment before having a rejected aliskiren claim were included. Patients were followed up for 6 months after the initial rejected aliskiren claim to see whether there was a therapy change. Therapy change was defined as titration of old regimens, fulfillment of aliskiren, or fulfillment of a new antihypertensive medication not used previously. A total of 1955 patients were identified (mean age, 64.5 years; 54.4% female). Six months after having rejected aliskiren claims, 36.8% overcame the utilization management and filled aliskiren; 45.1% filled a new antihypertensive medication not used previously; and 10.8% patients titrated old antihypertensive medications. More than one quarter of patients (28.4%) had no change in their antihypertensive treatment. Logistic regression analysis revealed that patients rejected because of prior authorization (odds ratio = 4.00 [95% CI, 1.89-8.44]) or step therapy (odds ratio = 2.59 [95% CI, 1.26-5.32]) were more likely to have a therapy change compared with patients rejected because of a restrictive formulary. A significant number of patients had no therapy change 6 months after having rejected aliskiren claims because of utilization management tools, indicating potential clinical inertia or lack of therapy intensification in hypertension management. Patients with restrictive formularies were least likely to have a therapy change. More aggressive follow-up with patients with a rejected claim may be warranted to reduce treatment gaps.


Geroprotection in the future. In memoriam of Joseph Knoll: The selegiline story continues.
In memoriam of Joseph Knoll: the selegiline story continues.


Consanguinity and its relationship to differential fertility and mortality in the Kotia: a tribal population of Andhra Pradesh, India.
Data on patterns of marriage, differential fertility and mortality were collected from 211 Kotia women residing in Visakhapatnam district of Andhra Pradesh, India. Consanguineous marriages made up just over a quarter of the total, and of these, father's sister's daughter (FSD) were more common than mother's brother's daughter (MBD). The mean inbreeding coefficient for the sample (F) was 0.0172. Women in consanguineous marriages had a lower mean number of total conceptions, live births and living offspring (net fertility) than women in non-consanguineous marriages. Significant heterogeneity was found in the means of living offspring for FSD, MBD and non-consanguineous couples, but not for conceptions and live births.


Flying after left ventricular assist device implantation.
Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face-to-face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty-five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty-five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.


Prolactin and amniotic fluid electrolytes.
Prolactin (PRL) levels and Na+, K+, Cl-, Ca++ concentrations in maternal serum and amniotic fluid from 64 women in normal term pregnancy were measured by immunoenzymetric assay and flame photometry. The mean amniotic fluid PRL concentration was 597.7 (SE 31.5) ng/ml and the mean amniotic fluid Na+, K+, Cl- and Ca++ levels were 125.6 (SE 0.9) mmol/l, 4.5 (SE 0.1) mmol/l, 109.3 (SE 1.3) mmol/l and 2.0 (SE 7.5 E-02) mmol/l, respectively. There was no correlation between PRL levels in maternal serum and amniotic fluid, and the electrolyte concentrations in amniotic fluid. A close correlation was found between the concentrations of Na+ and Cl- in maternal serum and amniotic fluid. Thus, even though PRL may participate in the regulation of electrolytes in the amniotic fluid compartments, our findings provide indirect evidence for the existence of other regulatory mechanisms.


Cobalamin and normal prions: a new horizon for cobalamin neurotrophism.
It is known that cobalamin (Cbl) deficiency damages myelin by increasing tumor necrosis factor (TNF)-α and decreasing epidermal growth factor (EGF) levels in rat central nervous system (CNS), and affects the peripheral nervous system (PNS) morphologically and functionally. It is also known that some polyneuropathies not due to Cbl deficiency are connected with increased TNF-α levels, and that various cytokines (including TNF-α) and growth factors regulate the in vitro synthesis of normal prions (PrP(C)s). Given that there is extensive evidence that PrP(C)s play a key role in the maintenance of CNS and PNS myelin, we investigated whether the PrP(C) octapeptide repeat (OR) region is involved in the pathogenesis of rat Cbl-deficient (Cbl-D) polyneuropathy. After intracerebroventricularly administering antibodies (Abs) against the OR region (OR-Abs) to Cbl-D rats to prevent myelin damage and maximum nerve conduction velocity (MNCV) abnormalities, and PrP(C)s to otherwise normal rats to reproduce PNS Cbl-D-like lesions, we measured PrP(C) levels and MNCV of the sciatic and tibial nerves. PrP(C) and TNF-α levels were increased in sciatic and tibial nerves of Cbl-D and saline-treated rats, and the OR-Abs normalized the myelin ultrastructure, TNF-α levels, and MNCV values of the sciatic and tibial nerves of Cbl-D rats. The same peripheral nerves of the otherwise normal PrP(C)-treated rats showed typical Cbl-D myelin lesions, significantly increased TNF-α levels, and significantly decreased MNCV values. These findings demonstrate that Cbl deficiency induces excess PrP(C)s and thereby excess OR regions, which seem to be responsible for the PNS myelin damage, as has recently been found in the case of CNS myelin damage [66]. Furthermore, excess TNF-α is also involved in the pathogenesis of Cbl-D polyneuropathy. In conclusion, we have extended the list of prion diseases by adding one caused by excess PrP(C)s and the polyneuropathies related to excess TNF-α.


ESR study of free and immobilized elastase.
Porcine pancreatic elastase (EC 188.8.131.52) has been immobilized on polyacrylamide beads using glutaraldehyde ad bridging reagent without important loss of catalytic activity. A nitroxide spin label, 1-oxyl-2,2,5,5-tetramethyl-4-piperidinyl-ethylphosphonofluoridate, reacting covalently with the serine-195 residue of the active centre of free elastase was used as a conformational and dynamical electron spin resonance probe. This signal is quenched by (Cu2+) which bind specifically at the active site at a distance of 7 A from the nitroxide group. This distance is not significantly affected by the fixation on the solid support. The electron spin resonance lineshape analysis indicates some mobility of the spin label with respect to the native protein. This restricted motion, which is pH dependent, is not noticeably modified by the immobilization of the enzyme. This immobilization has therefore induced no large conformational change of the protein in the vicinity of the active centre. Thermal denaturation of elastase in homogeneous solution is irreversible. Immobilization on the polyacrylamide beads results in 70% reversibility, but the temperature of denaturation is not modified.


[Fracture fixation of femoral neck fractures with adapted Zespol fixator. A preliminary report].
A mode of treatment for femoral neck fracture with the use of Zespol plate and two AO screws is presented. Seventeen patients from 32 to 89 years of age have been operated. The method employed allowed for early mobilization and further rehabilitation of the patients.


Cloning and nucleotide sequence of the gene braB coding for the sodium-coupled branched-chain amino acid carrier in Pseudomonas aeruginosa PAO.
The gene braB, encoding the Na(+)-coupled carrier for branched-chain amino acids in Pseudomonas aeruginosa PAO, was cloned on cosmid pMMB34. The cosmid clones carrying the braB gene were identified as those that restored growth at low leucine concentration and Na(+)-dependent leucine transport activity to P. aeruginosa PAO3536 defective in the transport of branched-chain amino acids. Determination of the nucleotide sequence of the DNA fragment shows that the braB gene comprises 1311 bp and encodes a hydrophobic protein of 437 amino acids with a calculated Mr of 45,279. The hydropathy profile suggests that there exist in the carrier protein 12 hydrophobic segments long enough to traverse the membrane. The amino acid sequence shows a high degree of homology with the brnQ product, a branched-chain amino acid carrier of Salmonella typhimurium, while no homology in the nucleotide sequences is found in the braB and brnQ genes.


HIV and liver diseases: recent clinical advances.
Because the life expectancy of patients infected with HIV has been prolonged, liver diseases have assumed far greater importance as a cause of morbidity and mortality in these patients. Given the shared risks of transmission, patients who have HIV often are coinfected with hepatotrophic viruses such as hepatitis C and hepatitis B. Further, antiretroviral therapy (ART) used by patients who have HIV is often hepatotoxic, contributing to liver damage. With increasing immunosuppression caused by AIDS, patients who have HIV have to deal with these issues and the increased risk of infection with opportunistic viral, fungal, bacterial, and protozoal pathogens. In addition, steatosis and lipodystrophy now are recognized more commonly in patients who have HIV, particularly in the setting of ART. Thus, understanding of liver diseases in the setting of HIV infection becomes an important focus in caring these individuals. There have been numerous advances in the treatment of liver disease in patients who have HIV, particularly in treating viral hepatitis C and B. This article reviews various liver manifestations in patients who have HIV and the recent advances in diagnostic and therapeutic options.


Sucrose cryo-protection facilitates imaging of whole eye sections by MALDI mass spectrometry.
Sucrose is used as a cryo-preservation agent on large mammalian eyes post formalin fixation and is shown to reduce freezing artefacts allowing the collection of 12-µm thick sections from these large aqueous samples. The suitability of this technique for use in MALDI imaging experiments is demonstrated by the acquisition of the first images of lipid distributions within whole sagittal porcine eye sections.


Do perennials really senesce?
Although senescence remains less studied in perennials than in monocarpic plants, major advances in understanding senescence in perennials have been achieved recently. This success is due not only to the use of genetic tools in woody plants but also to a renaissance of research on how perennials can live for centuries or even millennia. The particularities of perennial life are considered here, with an emphasis on how these affect senescence at different levels of organization. I conclude that although cellular and leaf senescence do share common features in monocarpic and perennial plants, the indeterminacy of meristems found in perennials begs the question of whether senescence really occurs in these organisms at the whole-plant level.


Sleep and circadian rhythms in affective patients isolated from external time cues.
Sleep electroencephalographic activity, circadian rhythms in motor activity and rectal temperature, and clinical state were monitored longitudinally in four affectively ill patients (two depressed, one manic, and one rapidly cycling between depression and mania) who lived in isolation from external time cues (zeitgebers) for 3 to 4 weeks. In these conditions it was possible to observe the intrinsic or free-running behavior of circadian pacemakers and thereby to test several hypotheses about the role of sleep and circadian rhythms in the pathogenesis of depression. No hypothesis was consistently supported by the results. We found that the intrinsic rhythm of a circadian pacemaker appeared to free-run with an abnormally fast frequency in one patient. No patient remained stably depressed during temporal isolation. Our experience suggests that this type of study can be carried out safely with appropriate precautions. Temporal isolation is a means to test decisively predictions of several chronobiological hypotheses about affective illness and should be applied to additional patients.


A closer look on the variety and abundance of the faecal resistome of wild boar.
Antimicrobial resistance (AMR) is a serious problem for public and animal health, and also for the environment. Monitoring and reporting the occurrence of AMR determinants and bacteria with the potential to disseminate is a priority for health surveillance programs around the world and critical to the One Health concept. Wildlife is a reservoir of AMR, and human activities can strongly influence their resistome. The main goal of this work was to study the resistome of wild boar faecal microbiome, one of the most important game species in Europe using metagenomic and culturing approaches. The most abundant genes identified by the high-throughput qPCR array encode mobile genetic elements, including integrons, which can promote the dissemination of AMR determinants. A diverse set of genes (n = 62) conferring resistance to several classes of antibiotics (ARGs), some of them included in the WHO list of critically important antimicrobials were also detected. The most abundant ARGs confer resistance to tetracyclines and aminoglycosides. The phenotypic resistance of E. coli and Enterococcus spp. were also investigated, and together supported the metagenomic results. As the wild boar is an omnivorous animal, it can be a disseminator of AMR bacteria and ARGs to livestock, humans, and the environment. This study supports that wild boar can be a key sentinel species in ecosystems surveillance and should be included in National Action Plans to fight AMR, adopting a One Health approach.


A novel method for defining the Greyhound talocrural joint axis of rotation for hinged transarticular external skeletal fixation.
In order to apply hinged transarticular external skeletal fixation for stabilization of the injured canine tarsal joint, knowledge of the three-dimensional (3D) location and orientation of the transverse axis is necessary. This method of immobilization may be used as a primary or adjunctive method of stabilisation for a large number of traumatic conditions. Using pin-mounted markers in the cadaveric Greyhound crus and talus, a closed-form solution of absolute orientation was used to identify, on radiographs, the lateral and medial locations of the transverse axis by tracking the 3D excursions of the markers during flexion and extension. A line was drawn across the dorsal aspect of the calcaneus from the most dorsal point on the distal articular surface(proximal intertarsal joint: PIJ) to the most dorsal point on its proximal articulation with the body of the talus, and the location of the centre of rotation was expressed in terms of the length of that line. In seven Greyhound tarsal joints, the medial end of the axis was located 73 ± 10% proximal to the PIJ and 11 ± 7% dorsal to the line. The lateral end was 73 ± 9% proximal tothe PIJ and -2 ± 3% plantar to the line.