The assessment of diviners and their knowledge by civil servants in southwestern Nigeria.
Belief systems are continuously being modified through the interpretations individuals give to the cultural order. The present study investigates the evaluations which educated Nigerians have of diviners and their knowledge claims. Two hundred civil servants in Abeokuta, a state capital in the Southwestern region, were asked to assess diviners. It was discovered that diviners are believed to have access to supernatural knowledge and that this knowledge is seen as medically useful. Further development of the diviner's knowledge was endorsed by 70% of the sample. The respondents were however ambivalent towards diviners as persons or the bearers of the knowledge. They (diviners) are believed to have become unduly materialistic and prone to dubious activities. The implications of these findings for social change were then considered.


Influence of ionising irradiation on clotrimazole in the solid state.
The effect of ionising irradiation on the antifungal drug clotrimazole has been studied. The compound was subjected to ionisation irradiation in the form of high-energy electron beam (25-800 kGy) from an accelerator. Before and after the irradiation the compound was subjected to the EPR, TLC, HPLC and HPLC-MS analysis. After irradiation with doses 400-800 kGy the colour of the substance was changed from white to cream. Four products of radiolysis appeared in the HPLC chromatogram at 7.7, 4.2, 6.4 and 14.6 min and the active ingredient content decreased to 96.5%. The irradiation with a dose of 25 kGy resulted in the appearance of trace amounts of the product at 7.7 min and free radicals (2.54 x 10(14)spins/g). On the basis of the HPLC-MS data, the main product of radiolysis (t(R)=7.7 min) is 1-(9-phenylfluoren-9-yl)-imidazole. Besides traces of (2-chlorophenyl)-diphenylmethanol, other impurities listed in the European Pharmacopoeia (European Pharmacopea, 5th edition, Council of Europe, Strasbourg, France, 2004.) have not been detected. Clotrimazole has been found to show relatively high resistance to ionising irradiation (greater than fluconazole) and probably will be suitable for radiation sterilisation but with doses lower than 25 kGy.


Joint processing of hartmann sensor and conventional image measurements to estimate large aberrations: theory and experimental results.
We report experimental results for what we believe to be a new technique for estimating aberrations that extends the strength of an aberration that may be sensed with Hartmann sensor technology by means of an algorithm that processes both a Hartmann sensor image and a conventional image formed with the same aberration. We find that the theory and the experiment match well within the experimental error and that strong defocus aberrations can be accurately sensed with this technique.


Immunosuppressive effect on T cell activation by interleukin-16- and interleukin-10-cDNA-double-transfected human squamous cell line.
It is well known that induction of immunotolerance with allogeneic skin transplantation is generally difficult. This study attempted to find an immunosuppressive protocol for skin allograft rejection involving interleukin-16 (IL-16) and interleukin-10 (IL-10), because both are known to inhibit mixed lymphocyte reaction (MLR). The data indicated that IL-16 enhanced the immunosuppressive effect of IL-10. IL-16-cDNA- and IL-10-cDNA-double-transfected squamous cell carcinoma cell line were used as an in vitro model and they produced more than 20 ng/ml of IL-16 and 100 pg/ml of IL-10 in the supernatant, which significantly inhibited MLR and also the activation of allogeneic lymphocytes, which were stimulated directly by allogeneic double-cDNA-transfectant cells. Thus allogeneic skin graft producing IL-16 and IL-10 might have a local immunosuppressive action that could prolong graft survival.


A retrospective study of cases of canine demodicosis submitted to a commercial diagnostic laboratory servicing the United Kingdom and Ireland (2017-2018): Part 1 - Signalment, lesion distribution, treatments, and concurrent diseases.
Canine demodicosis, due to an overpopulation of Demodex spp. mites, remains one of the most common dermatological diseases encountered in small animal practice. The aims of this study were to interrogate submitted histories and diagnostic report results from a large cohort of dogs (n = 508) diagnosed with demodicosis either through histological analysis or the finding of Demodex spp. mites on skin scrapings by a UKAS accredited commercial laboratory servicing the United Kingdom (UK) and Ireland in the years 2017 and 2018. The main findings revealed that short-coated breeds were more likely to develop juvenile-onset (JO) demodicosis, whereas medium- and long-coated breeds were more likely to develop adult-onset (AO) disease. Pododemodicosis was reported more commonly in adult, long-coated breeds. Skin scrapings were positive in only 83.3% of samples that had a corresponding positive biopsy result; this finding highlights the necessity to perform further diagnostic tests if demodicosis remains clinically suspected despite a negative skin scraping result. Concurrent underlying diseases, potentially associated with immunosuppression, were reported in 42/221 (19%) of dogs with AO demodicosis. Serum allergy and Sarcoptes ELISA assays were positive in individual animals in both the JO and AO groups; the clinical significance of these latter findings requires careful interpretation in dogs with confirmed demodicosis.


Eviscerated 'amyand' incisional hernia.
The presence of an inflamed appendix in an inguinal hernia sac is known as "Amyand" hernia. The appendix within an umbilical incisional hernia sac is rare, and its evisceration is even rarer. Here we report a case of spontaneous evisceration of an appendix through an umbilical incisional hernia following laparoscopic cholecystectomy.


Protective and Pathogenic Responses to Chikungunya Virus Infection.
Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naïve human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection.


The RAD50 gene of Saccharomyces cerevisiae is not essential for vegetative growth.
The gene RAD50 was located by the ability of subclones to restore the Rad+ phenotype following transformation of a rad50-1 mutant. Disruption of the gene was achieved by directed integration of a plasmid carrying a fragment internal to RAD50. Haploids with the disrupted gene are viable and do not differ in growth rate or plating efficiency from isogenic rad50-1 or Rad+ strains.


Lung CD103+ Dendritic cells of mice infected with Paracoccidioides brasiliensis contribute to Treg differentiation.
The DC subsets that express αE integrin (CD103) have been described to exert antagonistic functions, driving T cells towards either an inflammatory (Th1/Th17) or immunosuppressive phenotype (regulatory T cells - Treg). These functions depend on the tissue they reside and microenvironment factors or stimuli that this Antigen-presenting cell (APC) subpopulation receive. In this regard, immunoregulatory phenotype has been described in small subsets of CD103+ DCs from lung and intestinal mucosa. The function of this APC subpopulation in pulmonary Paracoccidioides brasiliensis infection is poorly described. Here, we showed that lung CD103+ DCs contribute to Treg differentiation in a pulmonary P. brasiliensis infection model, which was attributed to downregulation of costimulatory molecules analyzed in these APC subtypes 21 days post-infection. Overall, this data suggests that P. brasiliensis infection caused an immunosuppression that has also been observed in patients with the most severe form of Paracoccidioidomycosis (PCM) - a sickness caused by this fungus genus. Furthermore, these results open new perspectives for knowledge of the mechanisms that underlie the higher percentage of Treg cells found in peripheral blood of PCM patients.


A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy.
A group of 105 women (54 of whom were, and had only ever been, taking valproate for at least a year, and 51 who had only ever taken either lamotrigine or carbamazepine, for at least a year) were compared with a group of 50 women who did not have epilepsy: any oral contraceptive taken at the time of testing was recorded and blood levels of follicle stimulating hormone (FSH), luteinising hormone (LH), testosterone and prolactin were estimated from days 2 to 6 of the menstrual cycle (day 1 being the first day of bleeding) and an MRI scan made of their pelvis. Women with epilepsy in general were significantly more likely to exhibit evidence on MRI scanning, of polycystic ovaries (PCO): women taking valproate but not an oral contraceptive were significantly more likely to have clinical biochemical evidence of the polycystic ovarian syndrome (PCOS) with raised LH and/or testosterone levels between days 2 and 6 of their menstrual cycle than women who did not have epilepsy: this was not so for women taking lamotrigine or carbamazepine. Since the polycystic ovary syndrome has potentially serious consequences it is suggested that, where possible, valproate is avoided in women of child bearing potential.


Spectrophotometric assay for the quantitation of cell migration in the Boyden chamber chemotaxis assay.
The method described here for the quantitation of cell migration in Boyden chambers is applicable to many cell types, especially connective tissue cells and endothelial cells. Currently, there are many groups working toward the isolation of chemotactic factors for these cells and this method would be useful for the large numbers of repetitive assays done during a purification. In our hands the assay is very reproducible and can be learned within a short time. The major problem with the assay is that the upper surface cells must be completely removed as well as any cellular debris containing dye. However, if the proper care is used in removing these cells, the results vary less than those obtained by counting cells directly.


Peak oxygen uptake responses to training in obese adolescents: a multilevel allometric framework to partition the influence of body size and maturity status.
The influence of body size and maturation on the responses in peak oxygen uptake (VO2) to a 12-week aerobic training and nutritional intervention in obese boys (n = 30; 10-16 years) was examined using multilevel allometric regressions. Anthropometry, sexual maturity status, peak VO2, and body composition were measured pre- and postintervention. Significant decrements for body mass, body mass index z-score, and waist circumference and increments for stature, fat-free mass, and peak oxygen uptake were observed after intervention. Partitioning body size on peak VO2, the responses of the individuals to training were positive (11.8% to 12.7% for body mass; 7.6% to 8.1% for fat-free mass). Body mass and fat-free mass were found as significant explanatory variables, with an additional positive effect for chronological. The allometric coefficients (k') in the initial models were k' = 0.883 and k' = 1.058 for body mass and fat-free mass, respectively. The coefficients decreased when age was considered (k' = 0.530 for body mass; k' = 0.860 for fat-free mass). Including maturity indicator in the models was not significant, thus the influence of variability in sexual maturity status in responses to exercise-based intervention in peak VO2 may be mediated by the changes in body dimensions.


Drug-protein conjugates--XIII. The disposition of the benzylpenicilloyl hapten conjugated to albumin.
The disposition and metabolic fate of benzylpenicillin conjugated to a protein, human serum albumin (HSA), were compared with those of free penicillin in the rat. The conjugate was prepared by in vitro incubation of [3H]-benzylpenicillin and HSA at pH 10.8 for 24 hr at 37 degrees, conditions which favour the formation of penicilloyl-lysine residues. The synthetic conjugate was cleared more slowly from plasma than free penicillin after intravenous administration; thus at 3 hr, concentrations of 5.08 +/- 0.50% dose/ml of the conjugate (0.31 microCi; 2.92 mg protein) was obtained. In an earlier study a concentration of 0.03 +/- 0.01% dose/ml was obtained after administration of free BP (2.7 mmol kg-1). During this time, 1.41 +/- 0.50% of the conjugate dose was excreted in urine while 5.0 +/- 0.2% of the dose was excreted in bile. Tissue analysis indicated that the liver contained 15.3 +/- 0.9% of the dose, while other tissues contained less than 6% of the dose. In long term metabolism studies it was found that 39.5 +/- 1.0% and 46.5 +/- 0.9% of the dose (0.43 microCi; 6.33 mg protein) was excreted in the urine after 3 and 7 days respectively. The principal metabolite (63-68%) excreted in both bile and urine was identified on the basis of cochromatography and fast atom bombardment mass spectrometry as benzylpenicilloic acid, indicating that the conjugate undergoes specific cleavage at the bond between the benzylpenicilloyl moiety and the protein. In vitro degradation studies indicate that the metabolism occurs primarily in the liver. Therefore benzylpenicilloic acid excreted in urine, after administration of free BP, may be formed either by direct hydrolysis of the beta-lactam ring, and/or result from catabolism of protein conjugates formed in vivo.


The influence of penicillin on growth and morphology of Streptococcus pyogenes in vivo.
The influence of penicillin (pc) on the growth, phagocytosis and killing of Streptococcus pyogenes was studied for an M protein positive (M+) and an M protein negative (M-) strain in vivo as well as in vitro. In vivo studies were based on a tissue cage model and the analyses were performed by CFU determinations and electron microscopic investigations. The M- strain was easily phagocytized with and without pc, but killing only occurred after pc treatment and thus the number of viable bacteria rapidly decreased under the influence of pc. M+ streptococci were not reduced in numbers by pc-treatment in vivo, but morphological changes and at high pc concentrations, phagocytosis could be seen. When this strain (M+) was cultivated in the absence of pc, the phagocytic cells were totally destroyed - a reaction that was prevented by penicillin. Variations in surface morphology of the two strains seem to influence the differences in sensitivity to penicillin, phagocytosis and killing.


Roles of the N- and C-terminal domains of mammalian mitochondrial initiation factor 3 in protein biosynthesis.
Bacterial initiation factor 3 (IF3) is organized into N- and C-domains separated by a linker. Mitochondrial IF3 (IF3(mt)) has a similar domain organization, although both domains have extensions not found in the bacterial factors. Constructs of the N- and C-domains of IF3(mt) with and without the connecting linker were prepared. The K(d) values for the binding of full-length IF3(mt) and its C-domain with and without the linker to mitochondrial 28S subunits are 30, 60, and 95 nM, respectively, indicating that much of the ribosome binding interactions are mediated by the C-domain. However, the N-domain binds to 28S subunits with only a 10-fold lower affinity than full-length IF3(mt). This observation indicates that the N-domain of IF3(mt) has significant contacts with the protein-rich small subunit of mammalian mitochondrial ribosomes. The linker also plays a role in modulating the interactions between the 28S subunit and the factor; it is not just a physical connector between the two domains. The presence of the two domains and the linker may optimize the overall affinity of IF3(mt) for the ribosome. These results are in sharp contrast to observations with Escherichia coli IF3. Removal of the N-domain drastically reduces the activity of IF3(mt) in the dissociation of mitochondrial 55S ribosomes, although the C-domain itself retains some activity. This residual activity depends significantly on the linker region. The N-domain alone has no effect on the dissociation of ribosomes. Full-length IF3(mt) reduces the binding of fMet-tRNA to the 28S subunit in the absence of mRNA. Both the C-terminal extension and the linker are required for this effect. IF3(mt) promotes the formation of a binary complex between IF2(mt) and fMet-tRNA that may play an important role in mitochondrial protein synthesis. Both domains play a role promoting the formation of this complex.


Evaluation of different types of lamellar keratoplasty for treatment of peripheral corneal perforation.
To discuss the efficacy and visual outcomes of different types of lamellar keratoplasty (LK) for the treatment of peripheral corneal perforation. Sixty patients (67 eyes) with peripheral corneal perforation underwent semilunar LK (16 eyes), crescentic LK (12 eyes), biconvex LK (13 eyes), annular LK (11 eyes) and total LK (15 eyes) respectively. The applied type of LK for each involved eye was decided by different sizes and shapes of corneal ulceration and perforation. Postoperative visual acuity (VA), corneal astigmatism and postoperative complications were studied during a 7- to 21-month follow-up. VA showed no statistical difference preoperatively (P = 0.18), but it was statistically different postoperatively (P < 0.01) in eyes with different types of LK. Postoperative VA in eyes with semilunar LK, crescentic LK and total LK was statistically better than that before surgery (all P values <0.05). Postoperative corneal astigmatism in different types of LK was statistically different (P < 0.01). Semilunar and crescentic LK had the lowest astigmatism, while biconvex LK had the highest. The main postoperative complications were leakage at the graft-host interface, graft rejection and initial disease recurrence. LK is an effective procedure in eyes with peripheral corneal perforation. Different sizes and shapes of LK can influence postoperative VA due to different degrees of astigmatism. Yet postoperative astigmatism can be reduced by making well-matched grafts and preserving the uninvolved tissue to the largest extent.


Substrate activation and thermal denaturation kinetics of the tetrameric and the trypsin-generated monomeric forms of horse serum butyrylcholinesterase.
Native horse serum butyrylcholinesterase (acylcholine acylhydrolase; EC 184.108.40.206) is a tetrameric enzyme which can dissociate after a limited proteolysis by trypsin into three additional molecular forms, including the monomeric entity. The trypsin-generated monomer of butyrylcholinesterase, isolated by ultracentrifugation on sucrose gradient, is stable and allows the relations between the polymeric structure of butyrylcholinesterase and its kinetic characteristics to be approached, e.g., substrate activation and complex thermal denaturation curves. The trypsin-generated monomer of butyrylcholinesterase behaves with identical kinetic parameter values as the native tetrameric enzyme. On the other hand, the thermal denaturation of the native tetrameric butyrylcholinesterase does not follow first-order kinetics, but may be described by a sum of exponential terms. This behavior is not due to the polymeric nature of butyrylcholinesterase but seems to be related to a structural heterogeneity induced by the heat treatment.


Focal interictal epileptiform discharges in idiopathic generalized epilepsy.
Are idiopathic generalized epilepsies (IGEs) truly generalized? Do IGEs represent a continuum or rather distinct syndromes? Focal changes in the electroencephalography (EEG) have been reported in IGEs. The aim of this work is to investigate focal interictal epileptiform discharges (IEDs) in IGEs, and their relation to clinical variables. Forty-one IGE patients (classified according to ILAE, 2001) were recruited from a tertiary center (age 23 ± 10.938 years). Their files were reviewed and they were subjected to clinical examination and interictal EEG. Patients with focal IEDs were compared to those without focal IEDs. Nine patients had juvenile myoclonic epilepsy (JME) and 32 had idiopathic epilepsy with generalized tonic-clonic seizures only (EGTCSA). Focal IEDs were found in 20 patients, mostly in the frontal (45.5 %) and temporal (31.8 %) distribution. Patients with focal IEDs were treated with a larger number of combined antiepileptic drugs (AEDs) (p value = 0.022). No significant difference was found between the two groups regarding age, sex, age at onset, epilepsy syndrome, seizure frequency, family history, AEDs used (sodium valproate and carbamazepine) and their doses. Seventeen EGTCSA patients had focal IEDs. They were treated with larger number of combined AEDs (p value = 0.0142). No significant difference was found between the EGTCSA patients with and those without focal IEDs regarding age, sex, age at onset, seizure frequency, family history and AEDs doses. Caution must be applied in the interpretation of interictal focal IEDs. These focal changes may be related to prognosis, however this needs further investigation.


Computer assisted positioning of the proximal segment after sagittal split osteotomy of the mandible: Preclinical investigation of a novel electromagnetic navigation system.
Modifications of the temporomandibular joint position after mandible osteotomy are reluctantly accepted in orthognathic surgery. To tackle this problem, we developed a new navigation system using miniaturized electromagnetic sensors. Our imageless navigation approach is therefore optimized to avoid complications of previously proposed optical approaches such as the interference with established surgical procedures and the line of sight problem. High oblique sagittal split osteotomies were performed on 6 plastic skull mandibles in a laboratory under conditions comparable to the operating theatre. The subsequent condyle reposition was guided by an intuitive user interface and performed by electromagnetic navigation. To prove the suitability and accuracy of this novel approach for condyle navigation, the positions of 3 titanium marker screws placed on each of the proximal segments were compared using pre- and postoperative Cone Beam Computed Tomography (CBCT) imaging. Guided by the electromagnetic navigation system, positioning of the condyles was highly accurate in all dimensions. Translational discrepancies up to 0,65 mm and rotations up to 0,38° in mean could be measured postoperatively. There were no statistically significant differences between navigation results and CBCT measurements. The intuitive user interface provides a simple way to precisely restore the initial position and orientation of the proximal mandibular segments. Our electromagnetic navigation system therefore yields a promising approach for orthognathic surgery applications.


dRFEtools: dynamic recursive feature elimination for omics.
Advances in technology have generated larger omics datasets with potential applications for machine learning. In many datasets, however, cost and limited sample availability result in an excessively higher number of features as compared to observations. Moreover, biological processes are associated with networks of core and peripheral genes, while traditional feature selection approaches capture only core genes. To overcome these limitations, we present dRFEtools that implements dynamic recursive feature elimination (RFE), reducing computational time with high accuracy compared to standard RFE, expanding dynamic RFE to regression algorithms, and outputting the subsets of features that hold predictive power with and without peripheral features. dRFEtools integrates with scikit-learn (the popular Python machine learning platform) and thus provides new opportunities for dynamic RFE in large-scale omics data while enhancing its interpretability. dRFEtools is freely available on PyPI at https://pypi.org/project/drfetools/ or on GitHub https://github.com/LieberInstitute/dRFEtools, implemented in Python 3, and supported on Linux, Windows, and Mac OS.


Regional brain atrophy and cognitive decline depend on definition of subjective cognitive decline.
People with subjective cognitive decline (SCD) may be at increased risk for Alzheimer's disease (AD). However, not all studies have observed this increased risk. This project examined whether four common methods of defining SCD yields different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+ ) and without SCD (SCD-). Data from 273 Alzheimer's Disease Neuroimaging Initiative cognitively normal older adults were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Voxel-based logistic regressions were applied to deformation-based morphology results to determine if regional atrophy between SCD- and SCD+ differed by SCD definition. Linear mixed-effects models were used to evaluate differences in future cognitive decline. Results varied between the four methods of defining SCD. Left hippocampal grading was more similar to AD in SCD+ than SCD- when using the CCI (p = .041) and Worry (p = .021) definitions. The right (p=.008) and left (p=.003) superior temporal regions had smaller volumes in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer's Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment. These findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.


Stearoyl-CoA desaturases sustain cholinergic excitation and copulatory robustness in metabolically aging C. elegansmales.
Regulated metabolism is required for behaviors as adults age. To understand how lipid usage affects motor coordination, we studied male Caenorhabditis elegans copulation as a model of energy-intensive behavior. Copulation performance drops after 48 h of adulthood. We found that 12-24 h before behavioral decline, males prioritize exploring and copulation behavior over feeding, suggesting that catabolizing stored metabolites, such as lipids, occurs during this period. Because fat-6/7-encoded stearoyl-CoA desaturases are essential for converting the ingested fatty acids to lipid storage, we examined the copulation behavior and neural calcium transients of fat-6(lf); fat-7(lf) mutants. In wild-type males, intestinal and epithelial fat-6/7 expression increases during the first 48 h of adulthood. The fat-6(lf); fat-7(lf) behavioral and metabolic defects indicate that in aging wild-type males, the increased expression of stearoyl-CoA desaturases in the epidermis may indirectly modulate the levels of EAG-family K+ channels in the reproductive cholinergic neurons and muscles.


Low-Dose Estramustine Phosphate and Concomitant Low-Dose Acetylsalicylic Acid in Heavily Pretreated Patients With Advanced Castration-Resistant Prostate Cancer.
The aim of this phase 2 study was to evaluate the activity and tolerability of low-dose estramustine phosphate (EMP) with concomitant low-dose acetylsalicylic acid (ASA) as a thromboprophylactic agent in heavily pretreated patients with advanced castration-resistant prostate cancer. Patients received 420 mg of oral EMP twice daily and oral ASA 100 mg once daily. The primary endpoint was prostate-specific antigen response. All of the patients had been previously treated with docetaxel and abiraterone acetate, and 12 had also received cabazitaxel. Thirty-one patients were enrolled. Prostate-specific antigen response was observed in 9 patients (29.0%; 95% confidence interval [CI], 14-48). Median progression-free survival was 3.6 months (95% CI, 2.2-5.6), and median overall survival was 7.6 months (95% CI, 6.9-9.7). Treatment was generally well tolerated, and no grade 3/4 toxicity was observed. Ten patients (32.2%) had grade 2 nausea and vomiting. No cardiovascular event and no major bleeding occurred. No venous thromboembolism event was observed. Low-dose EMP with concomitant low-dose ASA seems to be a safe treatment option with some activity for patients with advanced castration-resistant prostate cancer who have been heavily pretreated.


Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA.
Understanding the mechanisms governing selective turnover of mutation-bearing mtDNA is fundamental to design therapeutic strategies against mtDNA diseases. Here, we show that specific mtDNA damage leads to an exacerbated mtDNA turnover, independent of canonical macroautophagy, but relying on lysosomal function and ATG5. Using proximity labeling and Twinkle as a nucleoid marker, we demonstrate that mtDNA damage induces membrane remodeling and endosomal recruitment in close proximity to mitochondrial nucleoid sub-compartments. Targeting of mitochondrial nucleoids is controlled by the ATAD3-SAMM50 axis, which is disrupted upon mtDNA damage. SAMM50 acts as a gatekeeper, influencing BAK clustering, controlling nucleoid release and facilitating transfer to endosomes. Here, VPS35 mediates maturation of early endosomes to late autophagy vesicles where degradation occurs. In addition, using a mouse model where mtDNA alterations cause impairment of muscle regeneration, we show that stimulation of lysosomal activity by rapamycin, selectively removes mtDNA deletions without affecting mtDNA copy number, ameliorating mitochondrial dysfunction. Taken together, our data demonstrates that upon mtDNA damage, mitochondrial nucleoids are eliminated outside the mitochondrial network through an endosomal-mitophagy pathway. With these results, we unveil the molecular players of a complex mechanism with multiple potential benefits to understand mtDNA related diseases, inherited, acquired or due to normal ageing.


The trichurid egg-shell: evidence in support of the Bouligand hypothesis of helicoidal architecture.
Electron microscopy of thin sections and freeze etch replicas of the eggs of the nematodes Trichuris suis and T. muris is used to provide evidence in support of the Bouligand hypothesis of helicoidal architecture. The evidence presented is as follows: 1. The specific objections to the Bouligand model raised by Dennell (1974) and Dalingwater (1975b) are answered by reference to a pyramid of helicoidal tissue in which the corners are blunt. 2. Sections cut normal to the plane of the laminae do not show parabolic patterning. Parabolae appear if the section is tilted--their direction depending upon the direction of tilting. 3. Freeze etching allows the direct visualization of helicoidal architecture. Fibres are parallel within any one lamina but the fibre direction rotates by an angle of 9 degrees in successive laminae. Parabolic arcs are made up of short lengths of straight fibres--curved fibres were not observed. Planes of sectioning producing single and double spiral artifacts are described and the formation of these artifacts discussed. The sense of rotation of the helicoid is shown to be asymmetrical about any mid-plane through the egg.


Clinical characteristics and outcomes of spontaneous bacterial peritonitis caused by Enterobacter species versus Escherichia coli: a matched case-control study.
Enterobacter species are important nosocomial pathogens, and there is growing concern about their ability to develop resistance during antimicrobial therapy. However, few data are available on the clinical characteristics and outcomes of Enterobacter spontaneous bacterial peritonitis (SBP). We retrospectively identified all patients with SBP caused by Enterobacter species admitted to a tertiary care hospital between January 1997 and December 2013. Each case was age- and sex-matched with four patients with Escherichia coli SBP. A total of 32 cases with Enterobacter SBP and 128 controls with E. coli SBP were included. Twenty-one (65.6 %) cases and 111 (86.7 %) controls had Child-Pugh class C (P = 0.006). Cases were significantly more likely to have hepatocellular carcinoma (65.6 % vs. 37.5 %, P = 0.004) and upper gastrointestinal bleeding (28.1 % vs. 9.4 %, P = 0.005). The initial response to empirical therapy (81.3 % vs. 81.2 %, P = 0.995) and the 30-day mortality (37.5 % vs. 28.9 %, P = 0.35) were not significantly different between the groups. Drug resistance emerged in one case and in no controls (4.3 % [1/23] vs. 0 % [0/98], P = 0.19). Compared with E. coli SBP, patients with Enterobacter SBP more frequently had hepatocellular carcinoma and upper gastrointestinal bleeding, yet clinical outcomes were comparable. Development of resistance during third-generation cephalosporin therapy was infrequent in patients with Enterobacter SBP.


Morphological Description and Clinical Implication of Sphenopalatine Foramen for Accurate Transnasal Sphenopalatine Ganglion Block: An Anatomical Study.
Transnasal sphenopalatine ganglion block is a commonly used approach for treatment of a variety of headache disorders. However, no standard technique has yet been defined for this less invasive approach. In this study, our aim was to investigate morphometric and anatomical features of the sphenopalatine foramen, and to describe a more efficient approach for transnasal sphenopalatine ganglion block. The present study was designed retrospectively. Ten cadaver semi- heads and 18 adult dry skulls (28 samples totally) were included in the study. The distances between the sphenopalatine foramen and palatum durum, and also between the sphenopalatine foramen and the spina nasalis anterior, angle of elevation of the sphenopalatine foramen from palatum durum, and the length and width of the sphenopalatine foramen were measured. The mean width and length of the foramen were 3.79±0.35 and 6.44±0.94 mm, respectively. The mean distance between the palatum durum and the sphenopalatine foramen was 15.58±1.68 mm. The mean angle of elevation of the sphenopalatine foramen from the palatum durum was 26.10±3.97 degrees. The mean distance between the sphenopalatine foramen and the anterior nasal spine was 52.90±2.98 mm. In the transnasal sphenopalatine block, we suggest advancement of nasal applicator through superolateral direction for approximately 5.3 cm, and at an angle of about 26° from the nasal base..


The activin signaling pathway promotes differentiation of dI3 interneurons in the spinal neural tube.
The generation of the appropriate types and numbers of mature neurons during the development of the spinal cord requires the careful coordination of patterning, proliferation, and differentiation. In the dorsal neural tube, this coordination is achieved by the combined action of multiple ligands of both the Wnt and TGF-beta families, and their effectors, such as the bHLH proteins. TGF-beta signaling acting through the BMP receptors is necessary for the generation of several dorsal interneuron types. Other TGF-beta ligands expressed in the dorsal neural tube interact with the Activin receptors, which signal via a different set of SMAD proteins than BMPs. The effects of Activin signaling on the developing neural tube have not been described. Here we have activated the Activin signal transduction pathway in a cell-autonomous manner in the developing chick neural tube. We find that a constitutively active Activin receptor promotes differentiation throughout the neural tube. Although most differentiated cell populations are unaffected by Activin signaling, the number of dorsal interneuron 3 (dI3) cells is specifically increased. Our data suggest that Activin signaling may promote the formation of the dI3 precursor cells within a region circumscribed by BMP signaling and that this function is not dependent upon BMP signaling.


Si-rich SiNx based Kerr switch enables optical data conversion up to 12 Gbit/s.
Silicon photonic interconnection on chip is the emerging issue for next-generation integrated circuits. With the Si-rich SiNx micro-ring based optical Kerr switch, we demonstrate for the first time the wavelength and format conversion of optical on-off-keying data with a bit-rate of 12 Gbit/s. The field-resonant nonlinear Kerr effect enhances the transient refractive index change when coupling the optical data-stream into the micro-ring through the bus waveguide. This effectively red-shifts the notched dip wavelength to cause the format preserved or inversed conversion of data carried by the on-resonant or off-resonant probe, respectively. The Si quantum dots doped Si-rich SiNx strengthens its nonlinear Kerr coefficient by two-orders of magnitude higher than that of bulk Si or Si3N4. The wavelength-converted and cross-amplitude-modulated probe data-stream at up to 12-Gbit/s through the Si-rich SiNx micro-ring with penalty of -7 dB on transmission has shown very promising applicability to all-optical communication networks.


Erratum: Endemic Indian clones of Klebsiella pneumoniae harbouring New Delhi metallo beta lactamase 1 on a hybrid plasmid replicon type: A case of changing New Delhi metallo beta lactamase plasmid landscapes in India?
[This corrects the article DOI: 10.4103/0255-0857.188314.].


Effectiveness of anisodamine for the treatment of critically ill patients with septic shock (ACIdoSIS study): study protocol for randomized controlled trial.
Septic shock is an important contributor of mortality in the intensive care unit (ICU). Although strenuous effort has been made to improve its outcome, the mortality rate is only marginally decreased. The present study aimed to investigate the effectiveness of anisodamine in the treatment of septic shock, in the hope that the drug will provide alternatives to the treatment of septic shock. The study is a multi-center randomized controlled clinical trial. Study population will include critically ill patients with septic shock requiring vasopressor use. Blocked randomization was performed where anisodamine and control treatments were allocated at random in a ratio of 1:1 in blocks of sizes 2, 4, 6, 8, and 10 to 354 subjects. Interim analysis will be performed. The primary study end point is the hospital mortality, and other secondary study endpoints include ICU mortality, length of stay in ICU and hospital, organ failure free days. Adverse events including new onset psychosis, urinary retention, significant hypotension and tachycardia will be reported. The study will provide new insight into the treatment of septic shock and can help to reduce mortality rate of septic shock. NCT02442440 (https://register.clinicaltrials.gov/).


Cutaneous toxicities of antiretroviral therapy for HIV: part II. Nonnucleoside reverse transcriptase inhibitors, entry and fusion inhibitors, integrase inhibitors, and immune reconstitution syndrome.
Cutaneous manifestations of antiretroviral medications for HIV are common and potentially dangerous conditions encountered by dermatologists. Part II of this two-part series on the cutaneous effects of antiretroviral medications for HIV will discuss the four most recent classes of medications that have been developed and immune reconstitution syndrome--an important diagnostic consideration when evaluating a dermatologic patient who is taking antiretroviral medications.


Misinformation on the Internet regarding Ablative Therapies for Prostate Cancer.
To evaluate the quality of web-based information on ablative therapies for prostate cancer. The 2 most common search engines (Google and Bing) were queried for the following terms: "prostate cancer" + "HIFU" and "cryotherapy," respectively. The top 50 websites for each were obtained. Websites were characterized and analyzed regarding their accuracy and completeness of information using criteria determined a priori. Academic papers were excluded. Of "HIFU" search results, 17% were advertisements, 13% and 29% were academic and private practice websites, respectively. Erroneous information on oncological efficacy was presented in 15% and 41% of academic and private practice websites, respectively. Criteria for treatment were mentioned in 31% and 66% of academic and private practice websites, respectively. Of "cryotherapy" search results, 18% were advertisements, 15% academic sites, and 11% private practices. Erroneous information was presented in 73% of both academic and private practice websites. Criteria for treatment were mentioned in 27% and 18% of these sites, respectively. Seventy eight percent and 75% of HIFU and cryotherapy sites, respectively, mentioned general side effects. There is substantial inaccurate and incomplete information on the Internet regarding ablative treatments for prostate cancer from academic and private practice websites. Selection criteria are uncommonly discussed. More attention to accuracy of information is needed to ensure patients are not misled about the data behind these treatments.


HPLC/ESI-MS identification of diastereomers of Impurity E - Degradation products of cefaclor.
A seven years old sample of cefaclor stored in room conditions, as a solid, has been analyzed by using high performence liquid chromatography/electrospray ionization-mass spectrometry. As a result of the sample degradation process, two diastereomers of Impurity E have been found to have formed. It is reasonable to assume that the diastereomers are formed due to the isomerization of C6 carbon atom. They have almost identical fragmentation patterns in both positive and negative ion mode. On the other hand, the diastereomers have different efficiencies of formation of dimer ions, under ESI conditions, especially in negative ion mode.


Incidence and risk factors of acromial fracture following reverse total shoulder arthroplasty.
The occurrence and related predictors of acromial fracture following reverse total shoulder arthroplasty (RTSA) have not been fully elucidated. The aim of this study was to determine the incidence and risk factors of acromial fractures after RTSA. We conducted a multicenter, retrospective case-control study of 787 cases (29 in acromial fracture group and 758 in control group) that underwent RTSA performed by 6 surgeons. The mean duration of follow-up after RTSA was 31.6 ± 21.8 months (range, 12-136 months). Demographic variables (age, sex, arm dominance, body mass index, working status, bone mineral density [BMD]), clinical variables (preoperative diagnosis, previous operation, implant design, preoperative clinical scores, screw size in glenoid fixation, postoperative rehabilitation), and radiographic variables (acromial thickness, critical shoulder angle, deltoid length, humeral offset to lateral acromion) were investigated. To determine risk correlation, univariate analysis and multivariate logistic regression analysis with calculated odds ratios (ORs) were performed. Postoperative acromial fractures occurred in 29 of the 787 shoulders with RTSA (3.7%). Acromial fractures were detected at a mean of 10.0 months (range, 1-66 months) postoperatively. Univariate analysis revealed that the occurrence of an acromial fracture was significantly associated with a previous operation (38% [11 of 29] vs. 21% [156 of 758], P = .025) and BMD (-2.33 vs. -1.74, P = .013). Multivariate logistic regression analysis found that the occurrence of a postoperative acromial fracture was significantly associated with a previous operation (P = .034; OR, 2.91; 95% confidence interval, 1.08-7.84) and deltoid length (P = .004; OR, 1.04; 95% confidence interval, 1.01-1.07). Acromial fracture following RTSA is not an uncommon complication, with an overall incidence of 3.7%. A previous operation, increased deltoid length, and low BMD were risk factors of acromial fracture following RTSA.


The Association Between Macroscopic Arteriosclerosis of the Renal Artery, Microscopic Arteriosclerosis, Organ Discard, and Kidney Transplant Outcome.
During organ retrieval, surgeons estimate the degree of arteriosclerosis and this plays an important role in decisions on organ acceptance. Our study aimed to elucidate the association between macroscopic renal artery arteriosclerosis, donor kidney discard, and transplant outcome. We selected all transplanted and discarded kidneys in the Netherlands between January 1, 2000, and December 31, 2015, from deceased donors aged 50 y and older, for which data on renal artery arteriosclerosis were available (n = 2610). The association between arteriosclerosis and kidney discard, the relation between arteriosclerosis and outcome, and the correlation between macroscopic and microscopic arteriosclerosis were explored. Macroscopic arteriosclerosis was independently associated with kidney discard (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.02-1.80; P = 0.03). Arteriosclerosis (any degree) was not significantly associated with delayed graft function (OR, 1.16; 95% CI, 0.94-1.43; P = 0.16), estimated glomerular filtration rate 1-y posttransplant (B, 0.58; 95% CI, -2.07 to 3.22; P = 0.67), and long-term graft survival (hazard ratio, 1.07; 95% CI, 0.86-1.33; P = 0.55). There was a significant association between mild arteriosclerosis and primary nonfunction (OR, 2.14; 95% CI, 1.19-3.84; P = 0.01). We found no correlation between macroscopic and histological arteriosclerosis, nor between histological arteriosclerosis and transplant outcome. Macroscopic arteriosclerosis of the renal artery was independently associated with kidney discard and somewhat associated with primary nonfunction posttransplant. However, there was no effect of arteriosclerosis on delayed graft function, estimated glomerular filtration rate at 1 y, or long-term graft survival. Our results are valid only after inevitable exclusion of discarded kidneys that had on average more arteriosclerosis. Hence, conclusions should be interpreted in the light of this potential bias.


Detours on the Road to Recovery: What Factors Delay Readiness to Return to Intended Oncologic Therapy (RIOT) After Liver Resection for Malignancy?
Poor recovery after oncologic hepatic resection delays Return to Intended Oncologic Therapy (RIOT) and shortens survival. In order to identify at-risk patients, this study was designed to determine which psychosocial and perioperative factors are associated with delayed RIOT readiness. A prospectively maintained database was queried to identify consecutive patients undergoing hepatectomy for malignancy from 2015 to 2017. Perioperative factors were compared between patients with early (≤ 28 postoperative days) vs. delayed (> 28 postoperative days) clearance to RIOT. Univariate analysis and multivariable logistic regression were performed. Of 114 patients, 76 patients (67%) had an open surgical approach, 32 (28%) had a major hepatectomy, and 6 (5%) had a major complication, with no mortalities. Eighty-two patients (72%) had early and 32 patients (28%) had delayed RIOT readiness. Patients with high preoperative symptom burden were more likely to have delayed RIOT readiness (OR 3.1, 95% CI 1.1-8.4, p = 0.024). On multivariable analysis, open surgical approach (OR 6.9, 95% CI 1.4-34.7, p = 0.018), length of stay > 5 days (OR 3.6, 95% CI 1.4-9.4, p = 0.010), and any complication (OR 3.4, 95% CI 1.1-10.7, p = 0.033) were associated with delayed RIOT readiness. Postoperative factors associated with delayed RIOT readiness included nutritional and wound-healing parameters. This study highlights the previously under-described importance of preoperative patient symptom burden on delayed postoperative recovery. As a cancer patient's return to oncologic therapy after hepatectomy has a substantial impact on survival, it is critical to adhere to enhanced recovery principles and address all other modifiable factors that delay recovery.


An insertion/deletion polymorphism in the gene encoding angiotensin converting enzyme is not associated with generalised vitiligo in an English population.
Vitiligo is an acquired hypomelanotic skin disorder characterised by circumscribed depigmented macules resulting from the loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a role in the pathogenesis of the disease. Recently, an insertion/deletion (I/D) polymorphism of a 287-base pair repetitive sequence in intron 16 of the angiotensin converting enzyme (ACE) gene has been associated with autoimmune disease and with the development of vitiligo. In this study, the distribution of ACE gene I/D genotypes was investigated in a population of 106 English patients with generalised (non-segmental) vitiligo and 174 ethnically matched healthy controls using a restriction fragment length polymorphism-polymerase chain reaction genotyping method. No significant difference in the frequencies of II, ID and DD genotypes was detected between vitiligo patients and control subjects (P=0.35). The same result was evident for the genotype distribution in vitiligo patients with an autoimmune disease and for those without when compared with controls (P=0.33 and P=0.53, respectively). In addition, the results indicated that the D allele was not significantly over-represented in the group of patients with vitiligo compared with controls (P=0.42) and that this was also the case for patients with and without associated autoimmunity (P=0.40 and P=0.62, respectively).


Radiation Therapy Dose Escalation in Unresectable Ewing Sarcoma: Final Results of a Phase 3 Randomized Controlled Trial.
Our aim was to assess the effect of radiation therapy (RT) dose escalation on outcomes in surgically unresectable Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET). Patients with nonmetastatic unresectable ES/PNET (excluding intracranial/chest wall) receiving vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide chemotherapy, planned for definitive RT, were accrued in this single-institution, open-label, phase 3 randomized controlled trial. Randomization was between standard dose RT (SDRT; 55.8 Gy/31 fractions/5 days a week) versus escalated dose RT (EDRT; 70.2 Gy/39 fractions/5 days a week) with a primary objective of improving local control (LC) by 17% (65%-82%). Secondary outcomes included disease-free survival (DFS), overall survival (OS), and functional outcomes by Musculoskeletal Tumor Society score. Between April 2005 and December 2015, 95 patients (SDRT 47 and EDRT 48) with a median age of 17 years (interquartile range, 13-23 years) were accrued. The majority of patients were male (59%). Pelvis was the most common site of primary disease (n = 60; 63%). The median largest tumor dimension (9.7 cm) and the median maximum standardized uptake value (8.2) on pretreatment fluorodeoxyglucose positron emission tomography-computed tomography were similar. At a median follow-up of 67 months, the 5-year LC, DFS, and OS for the entire cohort was 62.4%, 41.3%, and 51.9%, respectively. The 5-year LC was significantly better in EDRT compared with SDRT (76.4% vs 49.4%; P = .02). The differences in DFS and OS at 5 years (for EDRT vs SDRT) did not achieve statistical significance (DFS 46.7% vs 31.8%; P = .22 and OS 58.8% vs 45.4%; P = .08). There was a higher incidence of Radiation Therapy Oncology Group grade >2 skin toxic effects (acute) in the EDRT arm (10.4% vs 2.1%; P = .08) with excellent functional outcomes (median Musculoskeletal Tumor Society score = 29) in both arms. EDRT results in improved LC with good functional outcomes without a significant increase in toxic effects. Radiation dose escalation should be considered for surgically unresectable nonmetastatic ES/PNET.


Simultaneous, bilateral anterior ischemic optic neuropathy (AION) in polycythemia vera: a case report.
Polycythemia vera (PV) is a hemopoetic disorder. Apparently, although thrombosis accounts for the majority of morbidity, AION has not been associated with PV so far. PATIENT AND FINDINGS: A 63 y-old woman with PV was hospitalized because of acute liver failure. She also experienced bilateral painless loss of vision. Bilateral, pale optic disc swelling with flame-like hemorrhages, more pronounced in the right eye, constricted visual fields, and relative afferent papillary defect (RAPD) on the right side were present. Computer tomography scan revealed no signs of intraorbital pathology, elevated intracranial pressure or hemorrhages. We interpreted the findings as AION associated with the hyperviscosity syndrome. Liver transplantation had to be carried out in the next days. Three weeks later, vision improved slightly, but RAPD persisted, and disc pallor developed in both eyes. The patient died two months later. Central retinal artery and vein occlusions have been described as complications of Essential thrombocythemia, but not of PV. We observed a rare case of bilateral neuropathy suggestive of AION. This condition has so far not been associated with PV.


First add-on lacosamide treatment in children with focal epilepsy in China: A multi-centre real-life cohort study.
To assess the effectiveness and safety of lacosamide (LCM) as the first add-on therapy for children with focal epilepsy at multiple centres in China. Children aged 4-16 years with focal epilepsy from 13 epilepsy centres were included in this study. All patients were treated with LCM as the first add-on treatment and followed up for 26 weeks. The seizure frequency, seizure-free rate, ≥50% response rate, retention rate, and incidence of adverse drug reactions after the addition of LCM were analysed. Ninety-nine children (58 males; aged 4-16 years; mean age 8.51 ± 2.95 years) were enroled. The mean age at first seizure was 5.74 ± 3.12 years. All patients were administered LCM as the first add-on treatment for focal epilepsy. Twenty-eight patients (28/99, 28.28%) did not experience seizures during the follow-up period. The ≥50% response rates were 80.81% (80/99), 93.88% (92/98), 98.98% (97/98), and 100.0% (98/98) at 6 weeks (visit two), 10 weeks (visit three), 18 weeks (visit four), and 26 weeks (visit five), respectively, compared to that at baseline (visit one). The intelligence scores decreased in 12 participants, remained unchanged in 64, and increased in 16. Adverse events occurred in three participants during the trial, all of which were mild. LCM was effective as the first add-on therapy in this real-life multi-centre study of a paediatric population with focal epilepsy. Further prospective studies with long-term follow-up periods are needed to confirm the effectiveness and tolerability of LCM.


Predictors of inhibitor eradication by primary immune tolerance induction in severe haemophilia A with high responding inhibitors.
Immune tolerance induction (ITI) is the only proven strategy to eradicate factor VIII inhibitors in patients with haemophilia A (HA). To identify patients and treatment options with the highest chance of inhibitor eradication by primary ITI. In the frame of the Italian ITI Registry, carried out from 1995 to 2015 (last follow-up 2018), 137 primary ITI courses in severe HA patients (90/137 with poor prognosis) were analysed for predictors of outcome (complete/partial response or failure). Sixty-six of them (48%) were prospectively evaluated. ITI was successful in 91/137 patients (66.4%) and 70 (51.1%) achieved complete response within 11 months (median). Historical peak titres ≤200 BU/ml (P = .033), inhibitor titres ≤5 BU/ml at ITI start (P = .001), peak titres ≤100 BU/ml during ITI (P < .001) and missense mutations and small insertions/deletions of FVIII gene (P = .027) predicted complete inhibitor eradication. A score that considers the cumulative number of these variables predicted complete response with positive predictive values up to .81 at ITI start and .91 during ITI, respectively. Patients who had no bleeding (OR, 3.45, 95% CI: 1.4-8.6) nor other adverse events (OR 2.6, 95%CI: 1.3-5.3) during ITI had higher chances of complete response. During the 120-month follow-up (median), 2/70 patients who had achieved complete response relapsed (2.9%). This Registry, with a centralized review of outcomes, homogeneous data collection (half of which prospective) and long-term follow-up, provides insights for optimizing ITI, with a rationale for further studies in the currently evolving scenario of inhibitor management in HA patients.


DNA methylation profiling of pseudogene-parental gene pairs and two gene families.
A substantial proportion of human genes contain tissue-specifically DNA-methylated regions (TDMRs). However, little is known about the evolutionary conservation of differentially methylated loci, how they evolve, and the signals that regulate them. We have studied TDMR conservation in the PLG and TBX gene families and in 32 pseudogene-parental gene pairs. Among the members of the recently evolved PLG gene family, 5'-UTR methylation is conserved and inversely correlated with the cognate gene expression, indicating as well a conserved regulatory role of DNA methylation. Conversely, many genes of the much older TBX family display complementary tissue-specific methylation, suggesting an epigenetic complementation in the evolution of this gene family. Similar to gene families, unprocessed pseudogenes arose from gene duplications and we found TDMR conservation in some pseudogene-parental gene pairs displaying short evolutionary distances. However, for the majority of unprocessed pseudogenes and for all processed pseudogenes examined, we found that tissue-specific methylation arose de novo after gene duplication.


Defective auditory recognition after small hemorrhage in the inferior colliculi.
We report the case of a male patient with a traumatic small hemorrhage partially involving the bilateral inferior colliculi without evidence of a temporal lobe lesion. He was unable to comprehend spoken words although he had intact speech production, reading and writing abilities. Comprehension of environmental sounds was also affected. Among the receptive musical abilities, discrimination of intensity, tone and rhythm were preserved, while recognition of melody was impaired. Audiometry showed normal thresholds for pure tone. Waves I-IV of brainstem auditory evoked potentials were elicited normally, whereas the wave V was elicited with reduced amplitude and prolonged latencies on both sides. The main component of middle latency auditory evoked potentials, which is evoked over both hemispheres by monaural stimulation to either side in normal subjects, was elicited only over the hemisphere contralateral to the ear receiving stimulation. Our patient's auditory findings were similar to those usually found in generalized auditory agnosia. Auditory agnosia is usually considered as a sign of a bitemporal cortical or subcortical disorder, but, in our patient, a brainstem disorder caused a disturbance of auditory recognition similar to auditory agnosia due to a bitemporal lesion. Our patient's auditory findings may belong to the category of a brainstem auditory-processing disorder brought on by a small hemorrhage in the inferior colliculi. In addition, the impairment in our patient implies that, in the neural processing of musical parameters, the decoding of intensity, tone and rhythm is accomplished at the level of inferior colliculus, whereas further cortical processing is necessary for the appropriate recognition of melody.


Molecular weight distribution of phosphorus fraction of aquatic dissolved organic matter.
This study characterized dissolved organic phosphorus (DOP) that is discharged from the Everglades Agricultural Area as part of the larger pool of aquatic dissolved organic matter (DOM). Whole water samples collected at the Everglades stormwater treat area 1 West (STA-1 W) were fractionated using a batch ultrafiltration method to separate organic compounds based on apparent molecular weight (AMW). Each AMW fraction of DOM was characterized for phosphorus, carbon, nitrogen, UV absorbance, and fluorescence. The DOP content of the Everglades water matrix was characteristically variable constituting 4-56% of total phosphorus (TP) and demonstrated no correlation with dissolved organic carbon (DOC). Measured values for DOP exceeded 14μgL(-1) in four out of five sampling dates making phosphorus load reductions problematic for the stormwater treatment areas (STAs), which target inorganic phosphorus and have a goal of 10μgL(-1) as TP. The molecular weight distributions revealed 40% of DOP is high molecular weight, aromatic-rich DOM. The results of this research are expected to be of interest to environmental chemists, environmental engineers, and water resources managers because DOP presents a major obstacle to achieving TP levels <10μgL(-1).


[Effect of actinomycin D on the survival and recovery capacity of irradiated connective tissue cells in the Chinese hamster].
Simultaneous treatment of Chinese hamster fibroblasts with Actinomycin D and gamma rays under normal aerobic conditions leads to radiosensitization. In contrast to Actinomycin D pretreatment, modification to the effect of radiation is drug dose dependent in the case of post-treatment. No effect of Actinomycin D upon the shape of the radiation cell survival curve is seen under hypoxic conditions. Recovery from radiation damage in split dose experiments is not influenced by the drug.


Acceptability of screening for early detection of liver disease in hazardous/harmful drinkers in primary care.
It is estimated that one-quarter of adults in the UK drink at harmful/hazardous levels leading to increased mortality and alcohol liver disease (ALD). The Alcohol Liver Disease Detection Study (ALDDeS) aimed to test out in primary care the feasibility of alcohol misuse screening in adults, using the AUDIT questionnaire, and to assess screening harmful/hazardous alcohol users for ALD using newer non-invasive serum markers of fibrosis. To explore patients' experiences of taking part in ALDDeS and understanding of the delivery and process of screening for ALD using self-report questionnaires and feedback of liver fibrosis risk using levels of non-invasive serum markers. A nested qualitative study based in five primary care practices in the UK. From a sample of patients who were identified as drinking at harmful/hazardous levels, 30 participants were identified by maximum variation sampling for qualitative in-depth interviews. Using the principles of constant comparison the transcribed interviews were thematically analysed. Receiving a postal AUDIT questionnaire was viewed as acceptable by participants. For some completing the AUDIT increased awareness of their hazardous alcohol use and a positive blood test indicating liver fibrosis was a catalyst for behaviour change. For others, a negative blood test result provided a licence to continue drinking at hazardous levels. A limited understanding of safe drinking and of ALD was common. Educational and training needs of primary care professionals must be taken into account, so that patients with marker levels indicating low risk of fibrosis are correctly informed about the likely risks of continuing to drink at the same levels.


Influence of Fine Management Combined With PDCA Cycle Method on Disinfection Qualified Rate and Performance Grade of Ophthalmic Precision Instruments.
The aim of this study is to explore the influence of fine management combined with the plan-do-check-action (PDCA) cycle method on the management of ophthalmic precision instruments. The ophthalmic precision instruments centralized in the disinfection supply room of our hospital were selected as the research objects and divided into groups A and B. Traditional instrument management method was adopted in group A, and fine management combined with the PDCA cycle method based on the group A was adopted in group B. The instrument management risk scores, the qualified rate of disinfection, instrument performance grade, and incidence of toxic anterior segment syndrome (TASS) of the two groups were compared. The risk scores of instrument management and incidence of TASS in group B were lower than those in group A (p < 0.05). The qualified rate of disinfection and instrument performance grades in group B were higher than those in group A (p < 0.05). Fine management combined with the PDCA cycle method can improve the qualified rate of disinfection of ophthalmic precision instruments, optimize the performance of instruments, reduce the risk of instrument management, and reduce the incidence of TASS.


Occurrence of fumonisins in asparagus (asparagus officinalis L.) and garlic (allium sativum L.) from Germany.
Fusarium proliferatum is able to produce fumonisins and is considered a pathogen of many economically important plants (e.g. corn, rice, asparagus) [1]. The occurrence of fumonisin FB1 inF. proliferatum infected asparagus spears from Germany was investigated using a liquid chromatography/electrospray ionization-mass spectrometry (LC-ESI-MS) method with isotopically labeled fumonisin FB1-d6 as internal standard. Asparagus samples were harvested in July 2000 and screened forFusarium species. AltogetherF. oxysporum, F. proliferatum and F. sambucinum were isolated from the spears. The samples infected with F.proliferatum were subsequently analyzed for fumonisins. FB1 was detected in 9 of the 10 samples in amounts ranging from 36.4 ng/g to 4513.7 ng/g (based on dry weight). Fumonisins FB2 and FB3 were found in six samples in lower concentrations. In asparagus spears of June 2002 we could findF. proliferatum in 6% of the samples, however no fumonisins were detectable.Furthermore the capability of producing FB1 by the fungus in garlic bulbs was investigated. Therefore garlic was cultured inF. proliferatum contaminated soil and the bulbs were screened for infection with F.proliferatum and for the occurrence of fumonisins by LC-MS. F.proliferatum was detectable in the garlic tissue and all samples contained FB1 (26.0 ng/g to 94.6 ng/g).This is the first report of the natural occurrence of FB1 in German asparagus spears and furthermore our findings suggest a potential for natural contamination of garlic bulbs with fumonisins. For detailed results and methods see Ref. [2].


The relationship between serum IgG levels to subgingival gram-negative bacteria and degree of periodontal destruction.
The relationship between the serum IgG antibody titer against seven species of Gram-negative periodontopathic bacteria and clinical parameters (including plaque index, gingival index, periodontal pocket depth, and alveolar bone loss) was studied in 38 subjects. IgG antibody titer against the sonicated antigens was determined by micro-ELISA. A statistically significant correlation was found between the serum antibody titer against B. gingivalis and the degree of clinical parameters, especially pocket depth. The serum IgG levels against the seven micro-organisms in 16 periodontal patients before and after clinical treatment were also determined. Responses to B. gingivalis decreased (p less than 0.001), whereas responses to E. corrodens (p less than 0.01) increased slightly. No marked differences were noted between pre- and post-treatment sera in titers against B. intermedius, B. loescheii, F. nucleatum, A. actinomycetemcomitans, and C. ochracea.


Acidosis and coagulopathy: the differential effects on fibrinogen synthesis and breakdown in pigs.
Uncontrolled bleeding from coagulopathy signals imminent death in severely injured patients. Acidosis is an important predictor of coagulopathy, but the underlying contributing mechanisms are unclear. This study was designed to investigate the effects of acidosis on fibrinogen metabolism and coagulation function in a swine model. Twelve pigs were randomly divided into the control (n = 6) and acid (n = 6) groups. Acidosis of pH 7.1 was induced by infusion of 0.2 M HCl in lactated Ringer solution in the acid group. Afterward, an infusion of stable isotope 1-13C-phenylalanine (6 hours) and d5-phenylalanine (4 hours) was performed. Blood samples were withdrawn hourly to quantify fibrinogen synthesis and degradation rates using gas chromatograph and mass spectrometry analysis. To correlate changes in fibrinogen metabolism, coagulation changes were assessed by prolonged prothrombin time, partial activated thromboplastin time, activated clotting time, and thrombelastograph (TEG). Acidosis caused decreases in mean arterial pressure, arterial bicarbonate concentration, base excess, fibrinogen concentration, and platelet counts. Acidosis increased fibrinogen degradation rate from the control value of 4.3 +/- 1.0 mg/kg/h to 11.8 +/- 1.4 mg/kg/h (P < 0.05), with no effect on fibrinogen synthesis. Prolonged prothrombin time, partial activated thromboplastin time, activated clotting time were consistently prolonged by acidosis (all P < 0.05). Clotting rapidity (angle alpha in TEG) was decreased from a baseline value of 73.3 +/- 1.1 degree to 63.0 +/- 2.4 degree (P < 0.05). Clot strength (maximum amplitude in TEG) was decreased from a baseline value of 72.2 +/- 1.4 mm to 56.2 +/- 3.1 mm (P < 0.05). Acidosis compromised the clotting process and accelerated fibrinogen consumption with no effect on fibrinogen production, resulting in a deficit in fibrinogen availability.


Binding and internalization of 125I-Bolton-Hunter-substance-P by pancreatic acinar cells.
Binding of 125I-labelled Bolton-Hunter substance P (125I-BH-SP) to dispersed pancreatic acinar cells from guinea pigs was studied. Association of 125I-BH-SP to acinar cells was rapid, specific, and temperature-dependent. Dissociation of bound 125I-BH-SP was slow and 60 min after dilution only 12% of cell-associated radioactivity had dissociated from cells. Various c-terminal fragments of SP as well as structurally related substances inhibited binding. Bound 125I-BH-SP partly resisted acid washes of cells. After lysis of cells, cell-associated radioactivity was chromatographed on a Sephadex G-25 column. Part of radioactivity was eluted as apparently intact 125I-BH-SP. It is suggested that this material has been internalized into acinar cells.


Physician attitudes regarding the prescription of medical marijuana.
Surveys of physicians' attitudes regarding the therapeutic value of marijuana are rare. Drawing on a national sample of family physicians, general internists, obstetrician-gynecologists, psychiatrists, and addiction specialists, 960 (adjusted response rate 66%) offered opinions about the legal prescription of marijuana as medical therapy. Thirty-six percent believed prescribed marijuana should be legal and 26% were neutral to the proposition. Non-moralistic attitudes toward substance use were significantly associated with support for physician prescription, as was internal medicine and obstetrics-gynecology specialization. Physicians are, in general, less supportive than the general American public regarding the use of medical marijuana.


Interpersonal influence and disordered eating behaviors in adolescent girls: the role of peer modeling, social reinforcement, and body-related teasing.
This study investigated the association between interpersonal relationships, eating behaviors, and body esteem in a sample of adolescent girls. Participants included 876 girls who completed questionnaires regarding body esteem, eating behavior, peer pressure, and interpersonal relationships. Peer pressure was a strong predictor of eating behavior and body esteem after controlling for interpersonal variables. High externalized self-perceptions, self-reported teasing, and attributions about the importance of weight and shape for popularity and dating were important predictors of both body esteem and eating behavior. Also, girls who were nominated as popular by peers were more likely to engage in disordered eating and have lower body esteem. Results highlight the need for eating disorder prevention at the level of the peer group. Programs should focus on decreasing pressure to be thin, acceptance by peers for attributes other than appearance, and combating weight- and shape-related teasing within the school system.


The toxic effect of short exposures to the atmospheric oxygen concentration on early mouse embryonic development.
When culture conditions of mouse preembryos include an O2 concentration of 20%, preembryos that initiate in vitro culture at the 1-cell stage have a lower survival rate than preembryos that are harvested for culture at the 2-cell stage. This "toxic" effect of O2 is not seen at 5% O2 concentrations, suggesting that atmospheric O2 concentrations are toxic to preembryos. The present study examined the effect of short-term exposures to 20% O2, as may occur during in vitro fertilization procedures. The results demonstrated that when 1-cell preembryos were exposed to the atmospheric oxygen concentration for as little as 1 hour, their development was inhibited. Furthermore, such toxic effects did not become apparent until after four to five divisions. The authors conclude that it is critical to minimize exposure of zygotes to the atmospheric O2 concentration for optimal development to continue past the 8- to 16-cell stage, at least in the mouse.


Visualization of single receptor molecules bound to human rhinovirus under physiological conditions.
Dynamic force microscopy (DFM) was used to image human rhinovirus HRV2 alone and complexed with single receptor molecules under near physiological conditions. Specific and site-directed immobilization of HRV2 on a model cell membrane resulted in a crystalline arrangement of virus particles with hexagonal symmetry and 35 nm spacing. High-resolution imaging of the virus capsid revealed about 20 resolvable structural features with 3 nm diameters; this finding is in agreement with protrusions seen by cryo-electron microscopy. Binding of receptor molecules to individual virus particles was observed after injection of soluble receptors into the liquid cell. Virus-receptor complexes with zero, one, two, or three attached receptor molecules were resolved. The number of receptor molecules associated to virions increased over time. Occasionally, dissociation of single receptor molecules from viral particles was also observed.


Lactic acid production in mouse calvaria in vitro with and without parathyroid hormone stimulation: lack of acetazolamide effects.
The effect of acetazolamide on lactic acid production in mouse calvaria explants was examined in an attempt to explain in vivo inhibition of Ca mobilization from bone by sulfonamide inhibitors of carbonic anhydrase. Lactic acid production was evaluated in 8-10-week-old CD-1 mouse calvaria over a time period consistent with acetazolamide inhibition of both PTH-stimulated and nonstimulated Ca mobilization from bone in vivo. Labeled lactate, derived from [3,4-14C]glucose, and total lactate production were determined at 2-h intervals for up to 8 h. Simultaneous assessment of 14CO2 production and [14C]pyruvate levels established that acetazolamide produced no other related metabolic effects and that the drug did not block PTH stimulation of CO2 production. Acetazolamide (4.5 X 10(-4) M) was found to have no effect on labeled or total lactate production in mouse calvaria for up to 8 h of treatment. In addition, acetazolamide did not block PTH (10(-7) M) stimulation of lactate production. However, Cl 13,850 (10(-4) M), a structural analog of acetazolamide devoid of inhibitory activity on carbonic anhydrase or Ca mobilization from bone, was shown to significantly reduce lactate production from mouse calvaria. These results, therefore, suggest that acetazolamide does not inhibit Ca mobilization from bone through inhibition of lactic acid production and fail to support a mechanistic relationship between lactic acid production and Ca mobilization from bone.


Polyolefin-based electrospun fibrous matrices embedded with magnetic nanoparticles for effective removal of viscous oils.
In this work, we present a poly (ethylene-co-1-octene)-based fibrous matrix prepared via electrospinning for highly efficient removal of viscous oils. The sorbent consisting of linear low density polyethylene (LLDPE) allows selective absorption of crude oil spills at the water surface without the need for additional isolation of the matrix prior to the refining process. Moreover, the high specific pore volume of the LLDPE sorbent with uniform fibrous morphology was shown to enable the sorbent reach 81.5 ± 5.9% of its equilibrium absorption capacity within 5 min. Furthermore, magnetic nanoparticles (MNP) are incorporated into each fiber comprising the matrix to facilitate the recovery process via external magnetic field without altering the intrinsic absorption capacity. We envision that these sorbents offer a sustainable route for the quick and thorough clean-up of spilled oil due to their high absorption capacity, fast absorption rate, ease of recovery, and absence of secondary waste.


The prevalence of prostate carcinoma and its precursor in Hungary: an autopsy study.
The prevalence of incidental prostatic adenocarcinoma (PCa) and its precursor, high grade intraepithelial neoplasia (HGPIN) in an autopsy series from Hungarians (Central European Caucasians) was assessed and compared to similar data from the United States and European countries. Autopsy cases (n=139; 18-95 years) with no history of urological disease were histologically examined for prostate cancer and HGPIN. After en block removal, the prostate glands were fixed in formalin, sectioned at 3-5mm intervals and embedded in paraffin. Whole-mount serial sections were stained with Hematoxylin-eosin and examined for the presence of PCa and HGPIN. The frequency of PCa and HGPIN was compared to autopsy data obtained from other geographical areas. We found a 38.8% prevalence of incidental PCa with increasing age-related incidence. Both PCa and HGPIN are first detected in the 3rd decade and show a steady increase with age with respect to number of foci, tumor grade and volume. In the age group 81-95, 86.6% and 60% of men had PCa and HGPIN, respectively. Incidental PCa and HGPIN are very prevalent in Hungarian population, comparable with the high US and the Scandinavian epidemiological data for Caucasians.


The effect of androgen deprivation therapy on 68Ga-PSMA tracer uptake in non-metastatic prostate cancer patients.
To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate-specific membrane antigen (PSMA) tracer uptake demonstrated in 68Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer (PC) patients. The clinical data of 108 PC patients who received neoadjuvant ADT were retrospectively analyzed. All patients had a baseline 68Ga-PSMA-PET/CT scan, and a second scan was delivered median of 2.9 months after the initiation of ADT. The maximum standardized uptake value (SUVmax) of primary tumor (SUVp) and metastatic lymph nodes (SUVln) as well as PSA response were assessed between pre- and post-ADT 68Ga-PSMA-PET/CT scans. There were significant decreases in posttreatment serum PSA, SUVp, and SUVln. A decrease in SUVp was seen in 91 patients (84%) with a median value of 66% (range, 5-100%), while 17 patients (16%) had no change in or an increase in PSMA tracer uptake with a median value of 24% (range, 0-198%). Patients with Gleason score (GS) of 7 had significantly higher metabolic response rates compared to other patients. The disease progression was significantly higher only in patients with GS > 7 disease compared to GS 7 disease. The PSA response to ADT was the lowest in patients with ISUP high-grade tumors. A total of 16 patients (15%) had progressive disease, and in 9 patients (8%), radiotherapy decisions were modified according to posttreatment 68Ga-PSMA-PET/CT scans. The current study includes the largest number of patients analyzed to date and demonstrates that ADT causes a significant decrease in serum PSA values and SUVp and SUVln. The authors demonstrate that 68Ga-PSMA-PET/CT may be used as a quantitative imaging modality after neoadjuvant ADT in hormone-naïve non-metastatic PC patients.


Food, supplements, and fortified foods: scientific evaluations in regard to toxicology and nutrient bioavailability.
Food, supplements, and fortified foods can all be appropriate sources of nutrients. It is the responsibility of nutrition educators to help consumers use those nutrient sources appropriately. Consumers should consider at least six factors when they select foods, supplements, and fortified foods: flavor, convenience, cost, nutrient content, toxic factors, and bioavailability of nutrients. Consumers are often less concerned about the latter two factors than they should be. For example, many case histories have been published on the symptoms caused by overconsumption of vitamins A, B-6, C, and D and nicotinic acid. Generally those toxic symptoms were caused by the ingestion of supplements, not foods. Current widespread use of supplements containing one or two nutrients may not only cause overt toxicity symptoms but also adversely affect the bioavailability of other nutrients. For example, ingestion of excessive amounts of vitamin C appears to interfere with copper metabolism in human subjects; ingestion of high levels of zinc impairs immune function, depresses copper absorption, and induces anemia; consumption of supplemental calcium as calcium phosphate dibasic is associated with renal calcification in rats; and ingestion of supplemental magnesium depresses the apparent absorption of calcium and retention of calcium in bone by rats.


Rat pancreatic ribonuclease: agreement between the corrected amino acid sequence and the sequence derived from its messenger RNA.
A corrected amino acid sequence of rat pancreatic ribonuclease is presented which is in agreement with the messenger RNA sequence in [J. Biol. Chem. (1982) 257, 14582-14585]. The corrections do not change the general position of rat ribonuclease in trees which can be constructed for ribonuclease sequences, although they do place the rat sequence somewhat closer to the mouse sequence. The evolutionary rate of ribonuclease in the rodent family of the Muridae (rat and mouse) now has been calculated to be 140 nucleotide substitutions per 10(8) years per 100 codons, and still is one of the highest rates yet observed. The occurrence of 4 additional amino acids at the C-terminus in several mammalian ribonucleases is in agreement with the position of a second stop codon in the 3' non-coding region of the rat messenger RNA sequence.


Photosynthetic and growth response to fumigation with SO2 at elevated CO2 for C3 and C4 plants.
Six early successional plant species with differing photosynthetic pathways (3 C3 species and 3 C4 species) were grown at either 300, 600, or 1,200 ppm CO2 and at either 0.0 or 0.25 ppm SO2. Total plant growth increased with CO2 concentration for the C3 species and varied only slightly with CO2 for the C4 species. Fumigation with SO2 caused reduced growth of the C3 species at 300 ppm CO2 but not at the higher concentrations of CO2. Fumigation with SO2 reduced growth of the C4 species at high CO2 and increased growth at 300 ppm CO2. Leaf area increased with increasing CO2 for all plant species. Fumigation with SO2 reduced leaf area of C3 plants more at low CO2 than at high CO2 while leaf area of C4 plants was reduced more at high CO2 than at low CO2. These results support the notion that C3 species are more sensitive to SO2 fumigation than are C4 species at concentrations of CO2 equal to that found in normal ambient air. However, the difference in sensitivity to SO2 between C3 and C4 species was found to be reversed at higher concentrations of CO2. A possible explanation for this reversal based upon differences in stomatal response to elevated CO2 between C3 and C4 species is discussed.


Current status of the role of endothelins in regulating ovarian follicular function: A review.
Endothelins (EDN) are a group of vasoactive 21 amino acid peptides reported to play roles in steroidogenesis, folliculogenesis, and ovulation. EDN1, EDN2 and EDN3 have all been shown to affect granulosa cell (GC) function in a variety of mammalians species. Herewithin, the role of EDN in regulating steroidogenesis and ovarian follicular development is reviewed, focusing on the localization and function of EDN and their receptors in ovarian follicular function emphasizing species differences. For example, in single ovulating species such as humans and cattle, in the presence of trophic hormones such as FSH and IGF1, EDN1 and EDN2 significantly inhibited GC estradiol production in 2 of 4 studies, while no effect was observed for GC progesterone production in 2 of 4 studies. In contrast, EDN1 exhibited inhibitory effects on progesterone production by GC in 3 of 3 studies in pigs and 3 of 4 studies in rats. Also, EDN1 inhibited GC estradiol production in 4 of 5 studies in rats. Altogether, these results indicate that EDN are produced by ovarian follicles and are involved in the regulation of steroidogenesis of GC of several mammalian species including humans, cattle, pigs and rats, but that these effects may vary with species and culture condition.


Reconstruction of cropland cover changes in the Shandong Province over the past 300 years.
To advance global change research, it is essential to reconstruct changes in historical cropland coverage on a regional scale in China. This paper presents data collected from 244 local gazetteers, government statistical records and remote-sensing land cover data from the Shandong Province. The study reconstructed the spatial distribution of the rate of reclaimed land at the county level and compared this map with a map of the current spatial distribution of suitable cropland. The following conclusions were drawn: (i) The rate of cultivated land grew exponentially. The extent of reconstruction in cropland areas during the 17(th) century, 18(th)~19(th) centuries, the beginning of the 20(th) century, the 1980 s, and the beginning of the 20(th) century are 4.51 mha, 6.51 mha, 7.52 mha, 8.53 mha and 11.80-12.00 mha, respectively. (ii) Several agricultural centers formed during the late 17(th) century. Until the beginning of the 20(th) century, the reclamation rate increased rapidly near the four southern lakes, which are located in the Zaozhuang and Linyi regions. (iii) Most reclamation activities before the 19(th) century occurred in suitable agricultural areas, and the cultivated land was already reclaimed by the beginning of the 20(th) century.


Enhancing the utility of visitor impact assessment in parks and protected areas: a combined social-ecological approach.
Understanding the ecological consequences of visitor use in parks and how visitors interact with resource conditions is essential for avoiding the impairment of park and protected area resources and visitor experiences. This study combined ecological measures of off-trail resource impacts with social science techniques to understand visitor judgments of ecological impacts and visitors' degree of exposure to impacts. Specifically, this paper reports on a novel integration of techniques that was tested in the Bear Lake Road Corridor of Rocky Mountain National Park, CO, USA in which resource change, as a result of visitor use off designated trails and sites, was assessed and combined with social science and visitor use data. Visual survey techniques were used to understand visitor judgments of ecologically important resource impacts and GPS-tracking of visitor use and behavior allowed for the determination of the degree of visitor's exposure to impaired resources. Results suggest that resource impacts are prevalent and intense throughout the area, but tended to be spatially limited in proximity to attraction sites. Visitors are interacting with resource conditions reported to be unacceptable for significant portions of their hikes. Overall, the work represents an advancement of predictive capabilities when managing park and protected area resources.


Mouse pup urine as an infant signal.
Drops of urine from donors of different ages and sexes were applied to the anogenital regions of 19-day fetuses, killed by freezing, that ordinarily are weak in stimulating parental care. These fetuses were then presented to virgin, naive albino mice (Mus musculus). In Experiment 1, fetuses treated with urine of 6-day-old pups were more stimulating than fetuses treated with water. Differences in contact, picking-up, retrieval, licking and self grooming were significant. The sex of the donor revealed no effect. In Experiment 2, urine from 10-day-old pups was found to be more effective than urine from 4-day-old pups, with different effects on contact and retrieval. Urine from pups was also more effective than urine from adults, because of different effects on contact, picking-up, retrieval, licking and nest building. The effects of urine from adult virgin females differed less from those of pup urine than did the effects of urine from adult males. Compared with the latter the adult female urine had different effects on picking-up, licking and cannibalism. Speculations are made about an infant factor that might be still active in the urine of adult females.


Novel Peptides from Skins of Amphibians Showed Broad-Spectrum Antimicrobial Activities.
Peptide agents are often considered as potential biomaterials for developing new drugs that can overcome the rising resistance of pathogenic micro-organisms to classic antibiotic treatments. One key source of peptide agents is amphibian skin, as they provide a great deal of naturally occurring antimicrobial peptide (AMP) templates awaiting further exploitation and utilization. In this study, 12 novel AMPs from the skins of 3 ranid frogs, Rana limnocharis, R. exilispinosa, and Amolops afghanus, were identified using a 5' PCR primer. A total of 11 AMPs exhibited similarities with currently known AMP families, including brevinin-1, brevinin-2, esculentin-1, and nigrocin, besides, one AMP, named as Limnochariin, represented a novel AMP family. All 12 AMPs contain a C-terminus cyclic motif and most of them show obvious antimicrobial activities against 18 standard and clinically isolated strains of bacteria, including 4 Gram-positive bacteria, 11 Gram-negative bacteria, and 3 fungus. These findings provide helpful insight that will be useful in the design of anti-infective peptide agents.


Impact of spinal alignment and stiffness on impingement after total hip arthroplasty: a radiographic study of pre- and post-operative spinopelvic alignment.
Recent studies have revealed the impact of spinopelvic factors on the risk of dislocation after total hip arthroplasty (THA). This study examined the risk factors of impingement that can lead to dislocation using pre- and postoperative spinopelvic radiographs. We studied 143 consecutive patients with end-stage hip osteoarthritis who were eligible for THA at our institute. Pre-operative pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), sagittal vertical axis (SVA) in the standing and sitting position, and centre-edge angle (CE) were measured. The post-operative SS, LL, SVA, femoral shaft angle, and radiographic alignment of the acetabular component were also measured. We performed a multiple linear regression analysis to determine the risk factors for anterior and posterior impingement using pre-operative demographic and radiographic parameters. The clearance of anterior and posterior implant impingement was used for the surrogate-dependent variable for dislocation. A total of 95 patients were included in the analysis. There were significant differences in SS, LL, and SVA between the standing and sitting positions (P < 0.001). A multiple linear regression analysis showed that the PI-LL, LL changes, and CE were associated with the posterior impingement (β = - 0.21, 0.24, and -0.27, respectively). Moreover, PI-LL was also associated with the anterior impingement in the sitting position (β = - 0.27). Our results suggest that a flatback with a rigid spine leads to posterior impingement, and a well-balanced spine leads to anterior impingement, which can be a potential risk factor for dislocation.


Loop-mediated isothermal amplification assay targeting the mpb70 gene for rapid differential detection of Mycobacterium bovis.
Loop-mediated isothermal amplification (LAMP) is a highly sensitive, rapid, cost-effective nucleic acid amplification method. Tuberculosis (TB) is widely popular in the world and it is difficult to cure. The fundamental treatment is to clear the types of TB pathogens such as Mycobacterium bovis (M. bovis), Mycobacterium tuberculosis (M. tuberculosis). In order to detect and diagnose TB early, we constructed the differential diagnostic method of TB. In this study, we used LAMP for detection of M. bovis, based on amplification of the mpb70 gene which is a unique gene in M. bovis strain. The LAMP assay was able to detect only seven copies of the gene per reaction, whereas for the conventional PCR, it was 70 copies. The LAMP was evaluated for its specificity using six strains of five Mycobacterium species and 18 related non-Mycobacterium microorganism strains as controls. The target three Mycobacterium strains were all amplified, and no cross-reaction was found with 18 non-Mycobacterium microorganism strains. TB was detected by two methods, LAMP and conventional PCR (based on mpb70 gene); the positive rates of the two methods were 9.55 and 7.01 %, respectively. Our results indicate that the LAMP method should be a potential tool with high convenience, rapidity, sensitivity and specificity for the diagnosis of TB caused by M. bovis. Most importance is that the use of LAMP as diagnostic method in association with diagnostic tests based on mpb70 gene would allow the differentiation between M. bovis and other Mycobacterium in humans or animals. The LAMP method is actually in order to detect human TB, and it can be used for differential diagnosis in this paper.


Pollution Characteristics, Sources, and Health Risk Assessments of Potentially Toxic Elements in Community Garden Soil of Lin'an, Zhejiang, China.
The characteristics, sources and risk assessment of heavy metal pollution in community garden soil of Lin'an District were evaluated. The 28 soil samples from community garden were collected for determination of 7 heavy metal elements. The Geostatistical analysis, Spearman correlation coefficient, Principal component analysis and PMF model have explored sources of heavy metal pollution. The health risk assessment model has assessed ecological risk of heavy metals. The results revealed that average concentration of As, Cd, Cr, Cu, Ni, Pb and Zn were 16.0, 0.158, 76.1, 34.6, 45.8, 20.9 and 166 mg kg-1, respectively. Whereas As, Cd, Cr, Cu, Ni and Zn were higher than background values. The spatial distribution of heavy metal pollution in the southwest of the study area was higher than northeast. The pollution sources of Cd, Cu, Ni and Zn in the study area were due to agricultural activities (42.9%), Cr and Pb were from traffic sources (36.2%), and As was domestic pollution (20.9%) according to Spearman correlation coefficient, Principal component analysis and PMF model. The non-carcinogenic risks of As (5.39), Cr (3.53) and Ni (2.07) have a value of 1, which indicated significant risk. The potentially toxic elements have not exceeded maximum threshold of USEPA, with regard to carcinogenic risk, while As (3.37E-05) and Cr (5.74E-05) have exceeded the safety range. It is concluded that soils of community gardens are facing pollution problem due to potentially toxic elements which require environmental monitoring of the soil to reduce risk of human health.


A wintertime investigation of atmospheric deposition of metals and polycyclic aromatic hydrocarbons in the Athabasca Oil Sands Region, Canada.
With planned expansion of oil sands facilities, there is interest in being able to characterize the magnitude and extent of deposition of metals and polycyclic aromatic hydrocarbons (PAH) in the Athabasca Oil Sands Region (AOSR) of Alberta. A study was undertaken using a bulk collection system to characterize wintertime atmospheric deposition of selected inorganic and organic contaminants in the AOSR. The study was carried out from January to March 2012 at two sampling sites near (within a 20 km circle of oil sands development) and two sampling sites distant (>45 km) to oil sands development. Triplicate bulk samplers were used to estimate precision of the method at one distant site. Monthly deposition samples were analyzed for 36 metals, ultra-low mercury, and 25 PAHs (including alkylated, and parent PAH). At the two sites located within 20 km of oil sands development, 3-month wintertime integrated deposition for some priority metals, alkylated and parent PAH were higher compared to distant sites. Deposition fluxes of metals and PAH were compared to other available bulk deposition studies worldwide. Median bulk measurement uncertainties of metals and both PAH classes were 26% and within ±15%, respectively suggesting that the bulk sampling method is a potential alternative for obtaining future direct measures of wintertime metals and PAH deposition at locations without access to power in the AOSR.


Diaphragm recovery by laryngeal innervation after bilateral phrenicotomy or complete C2 spinal section in rats.
This study aimed to highlight the functional aspects of diaphragm reinnervation by laryngeal motoneurons after bilateral phrenicotomy or complete cervical transection. The left recurrent laryngeal nerve was connected to the left phrenic nerve in 14 rats. Five months later, all bridged rats presented a substantial ipsilateral diaphragm recovery (74.2 +/- 10% of contralateral activity) whereas the diaphragm remained paralysed in non-bridged rats (n = 5/5). After additional right phrenicotomy, functional breathing persisted in bridged rats whereas all non-bridged died. After complete C2 spinal transection, diaphragm respiratory discharges persisted in bridged rats. The reinnnervation by laryngeal motoneurons was confirmed by retrograde labeling, stimulus-elicited diaphragm response by vagal stimulation and diaphragm inactivation after vagotomy. In conclusion, the recurrent-phrenic nerve anastomosis induces a reliable functional diaphragm outcome even after contralateral diaphragm denervation or complete high cervical spinal cord injury, and could be considered as a clinical repair strategy for re-establishing diaphragm autonomy following spinal cord trauma.