Effect of environmental temperature on the vector competence of Aedes fowleri for Rift Valley fever virus.
Studies were conducted to determine the effect of environmental temperature on the ability of Senegalese Aedes fowleri to transmit Rift Valley fever (RVF) virus. Temperatures tested included 17 degrees C, 28 degrees C and a cyclic (17-28 degrees C) regimen designed to mimic temperatures to which a mosquito might be exposed in October in southeastern Senegal. After per oral exposure, infection rates were similar (ca. 93%) for all three groups. However, RVF virus disseminated to the haemocoel more rapidly in mosquitoes held at higher temperatures, with peak dissemination rates (ca. 80%) reached at 11, 18 and greater than 42 days after the infectious blood meal for mosquitoes held at 28 degrees C, cyclic and 17 degrees C, respectively. Likewise, the time interval between ingestion of the viremic blood meal and the first transmission by bite was inversely related to environmental temperature, with the first transmission occurring at 11, 18 and 35 days for mosquitoes held at 28 degrees C, cyclic and 17 degrees C, respectively. After being transferred from 17 to 28 degrees C on days 7 or 14 after the infectious blood meal, mosquitoes rapidly developed a disseminated infection and transmitted virus by bite within 7 days. Environmental temperature significantly affected the vectorial capacity of A. fowleri for RVF virus, with transmission occurring earlier and at a higher rate in mosquitoes held at higher temperatures.


Randomized, single-blind, placebo-controlled trial on Hominis placenta extract pharmacopuncture for hot flashes in peri- and post-menopausal women.
Hominis placenta pharmacopuncture is widely used for climacteric symptoms. This study examined the efficacy and safety of pharmacopuncture with PLC (the extract of Hominis placenta) on hot flashes for perimenopausal and postmenopausal women. This study was a randomized placebo-controlled single-blind trial, which recruited 128 perimenopausal and postmenopausal women, randomly assigned to receive pharmacopuncture with PLC or normal saline (NS) for eight weeks. The primary outcome was the mean changes in the hot flash score (HFS) and the secondary outcomes were the mean changes in the Menopause Rating Scale (MRS), follicle-stimulating hormone (FSH) levels, and estradiol (E2) levels from baseline to eight weeks. Missing values were imputed using the last-observation-carried-forward method. After treatment (week 9), the HFS decreased significantly in both groups (p = 0.000). The residual HFS was 47.09 ± 41.39% and 56.45 ± 44.92 % in the PLC and control groups, respectively (p = 0.262). One month after the treatment (week 13), the score of the PLC group was reduced, but the score increased in the control group (p = 0.077). There were no statistically significant differences in the mean changes in MRS, FSH, and E2 between the two groups. No serious adverse events related to this trial were noted. In this study, Hominis placenta extract pharmacopuncture did not differ significantly from NS in reducing the hot flash score. While this therapy appears safe, the potential for long-term effect of PLC extract needs to be examined in a large randomized controlled trial with appropriate controls.


Effects of Phyllanthus amarus extract on nonspecific immune responses, growth, and resistance to Vibrio alginolyticus in white shrimp Litopenaeus vannamei.
This study investigates the effects of Phyllanthus amarus extract (PAE) on immune responses, growth, and resistance to Vibrio alginolyticus in white shrimp (Litopenaeus vannamei). In vitro PAE treatment did not alter the cell viability of haemocytes and significantly enhanced immune parameters such as phenoloxidase (PO) activity, phagocytic activity, and superoxide anion (O2-) production. We conducted two feeding trials to examine the effects of PAE on the growth, disease resistance, and innate immune parameters of white shrimp. In the first in vivo trial, shrimps (4.01 ± 0.03 g) were fed a diet containing 0 g (control), 10 g (PAE10), 20 g (PAE20), or 40 g (PAE40) of PAE per kilogram of feed for 56 days. After the feeding period, the PAE20 group showed a significantly higher weight gain and specific growth rate than shrimp fed the control diet. Furthermore, after challenge with V. alginolyticus, shrimp fed a diet containing PAE showed significantly higher survival than those fed the control diet. The second in vivo trial (28 days) was performed to identify the mechanisms of enhanced immunity in PAE-fed shrimp. Shrimp fed the PAE20 diet generally had the highest total haemocyte count, PO activity, phagocytic activity, and O2- production, followed by the PAE40 and PAE10 groups. Thus, our results suggest that administration of 20 g of PAE per kilogram of feed can enhance immunity, growth, and resistance to V. alginolyticus in white shrimp.


Early social instability affects plasma testosterone during adolescence but does not alter reproductive capacity or measures of stress later in life.
The social environment plays an important role in modulating processes of the hormonal and behavioural profile of an animal in a variety of group-living species. In wild cavies for instance, unstable social environmental conditions during pregnancy and lactation lead to an infantilised biobehavioural profile of the male offspring. In the present study, the influence of the social environment during pregnancy and lactation on the male wild cavy offsprings' plasma testosterone development, reproductive capacity and stress system activity was investigated. To this purpose, 12 sons whose mothers had lived in an unstable social environment during pregnancy and lactation were compared with 12 sons whose mothers had lived in a stable social environment during the same time. Plasma testosterone (T) and plasma cortisol (C) concentrations were determined from days 20 to 107 of age. Adrenal tyrosine hydroxylase (TH) activity and different parameters of reproductive capacity (weights of testes, epididymides and accessory sex glands, cellular composition of the testes, DNA fragmentation indices and sperm motility parameters) were analysed at day 107 of age. TH activity and plasma C were unaffected by different social environmental conditions early in life. The developmental time course of T concentrations, however, was significantly different: Sons whose mothers had lived in an unstable social environment during pregnancy and lactation showed a delayed increase in T concentrations around adolescence compared to controls. In contrast, no reproduction-related parameters measured within this study differed significantly between the two groups. Thus, early social instability affects plasma testosterone development during adolescence in a significant way but does not alter reproductive capacity or measures of stress later in life.


Cux1 transcription factor is induced in inflammatory bowel disease and protects against experimental colitis.
Cux1 is a ubiquitous transcriptional factor that has been associated with cell proliferation, migration, invasion, and differentiation. Cux1 is an effector of the transforming growth factor beta (TGFβ) pathway, PAR(2) receptor signaling, and cellular migration, mechanisms intimately related to inflammatory bowel diseases (IBD). CD1 mice treated with dextran sulfate sodium (DSS) in drinking water and cultured intestinal epithelial cells were used to determine Cux1 expression under inflammatory conditions. A commercial cDNA library was used to monitor CUX1 expression in IBD patients. The Cux1(ΔHD/ΔHD) hypomorphic mouse model (Cux1ΔHD) treated with DSS in drinking water was used and the disease severity assessed. Cux1 expression increased in cultured intestinal epithelial cells stimulated with tumor necrosis factor alpha (TNFα), in the mouse intestinal epithelium during experimental colitis and in human IBD patient samples. DSS-induced colitis in Cux1ΔHD mice was more severe according to clinical observations such as weight loss, colon length, and rectal bleeding. Histological observations confirmed an increase of IBD-related morphological changes including ulceration and mucosal infiltration of leukocytes in Cux1ΔHD mice. An increased number of pSer(276)-RelA-positive cells and higher expression levels of proinflammatory cytokines were also measured in the colon of Cux1ΔHD diseased animals. Elevated levels of Cxcl1 were measured before and after DSS-treatment and a greater neutrophilic infiltration was quantified in DSS-treated Cux1ΔHD mice. Finally, mucosal healing was significantly impaired in Cux1ΔHD mice during recovery from DSS treatment. CUX1 is increased in response to inflammatory stress and its nuclear expression is crucial to protect against DSS-induced colitis and subsequent mucosal healing.


Dynamics of collinear contrast facilitation are consistent with long-range horizontal striate transmission.
It is well established that activity of striate neurons may be either facilitated or suppressed by visual stimuli presented outside of their classical receptive field (CRF) limits. Whilst two general mechanisms have been identified as candidates for these contextual effects; those based on extra-striate feedback and long-range horizontal striate connections; the physiological data supporting these models is both ambiguous and inconsistent. Here we investigate psychophysically the phenomenon of collinear facilitation, in which contrast detection thresholds for foveally presented Gabor stimuli are reduced via concurrent presentation of remote collinear flankers. Using backward noise masking, we demonstrate that the minimum exposure duration required to induce facilitation increases monotonically with greater target-flanker separation. The inferred cortical propagation velocities of this process (0.10-0.23 ms(-1)) closely correspond with depolarising activity observed to travel across striate cortex of several species. These dynamics strongly suggest that contrast facilitation is mediated via long-range horizontal striate connections. This conclusion complements a recent suggestion that collinear induced long-range suppressive dynamics depend on extra-striate feedback.


Multivariate Normative Comparison, a Novel Method for Improved Use of Retinal Nerve Fiber Layer Thickness to Detect Early Glaucoma.
Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). This study assessed whether compensating the RNFL thickness for multiple demographic and anatomic factors improves the detection of glaucoma. Cross-sectional study. Three hundred eighty-seven patients with glaucoma and 2699 healthy participants. Two thousand six hundred ninety-nine healthy participants were enrolled to construct and test a multivariate compensation model, which then was applied in 387 healthy participants and 387 patients with glaucoma (early glaucoma, n = 219; moderate glaucoma, n = 97; and advanced glaucoma, n = 71). Participants underwent Cirrus spectral-domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. The RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. Measured and compensated RNFL thickness measurements. After applying the Asian-specific compensation model, the standard deviation of RNFL thickness reduced, where the effect was greatest for Chinese participants (16.9%), followed by Malay participants (13.9%), and Indian participants (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC, 0.90 vs. 0.85; P < 0.001), moderate glaucoma (AUC, 0.94 vs. 0.91; P < 0.001), and advanced glaucoma (AUC, 0.98 vs. 0.96; P < 0.001). The multivariate normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting that accounting for demographic and anatomic variance in RNFL thickness may have usefulness in improving glaucoma detection.


Systemic evaluation of patients with central serous chorioretinopathy: A case-control study.
To investigate the systemic associations of central serous chorioretinopathy (CSCR) with help of clinical and biochemical investigations. Case-control study. Eighty seven CSCR patients (case) and 82 Asian-Indian patients with primary non-traumatic rhegmatogenous retinal detachment (control) were recruited between July 2017 and December 2018 at a tertiary eye-care center in North India. The patients underwent ophthalmological examination and systemic evaluation based on history and biochemical investigations. Logistic regression was performed to identify the associations of CSCR. The age was similar between cases and controls (36.9 ± 7.8 years vs 35.7 ± 10.8 years, p = 0.38). On univariate analysis, the significant factors with higher odds of CSCR were alcohol use (odds ratio, OR: 3.4; 95% confidence interval: 1.36-8.53), sleep disturbance (OR: 5.44; 1.76-16.8), gastroesophageal reflux (OR: 9.34; 1.15-75.50), psychological disorder (OR: 5.78; 1.24-26.97), tuberculosis history (OR: 8.2; 1.0-67.10), serum albumin: globulin ratio (AGR) > 2 (OR: 10.43; 2.33-46.57), and serum hemoglobin (per unit increase; OR: 1.35; 1.14-1.61). Although the mean blood pressure was significantly higher in cases, the distribution among various hypertension categories was not significantly different. Exogenous steroid use and morning 8 am serum cortisol levels were not significantly different between the groups. On multivariable analysis, alcohol use (OR: 4.72; 1.33-16.76), sleep disturbances (OR: 5.04; 1.36-18.70), dysthyroid state (OR: 3.02; 1.04-8.74), serum AGR > 2 (OR: 14.28; 2.33-87.28), and serum hemoglobin (per unit increase; OR: 1.43; 1.13-1.81) were significant independent associations. Other than the previously described associations of CSCR like alcohol use and sleep disturbances, this study reports possible association with deranged serum protein and thyroid hormone profile. Further large-scale prospective studies need to validate these results.


Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.
Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptide A (H-WRQNTRYSRIEAIKIQILSKLRL-NH2 ), the 23-amino-acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N-terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhibitors. As a result of the investigation, a more potent derivative of peptide A was successfully identified in which the N-terminal tryptophan residue is replaced with a 2-naphthyloxyacetyl moiety to give an inhibitory peptide three times (1.19±0.11 μm) more potent than parent peptide A (3.53±0.25 μm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides.


Endovascular stent-graft treatment for Stanford type A aortic dissection.
The aim of the study is to summarise our experience of endovascular stent grafting for Stanford type A aortic dissection. Retrospective analysis at single centre. From January 2001 to January 2009, we treated 45 cases of Stanford type A aortic dissection with endovascular stent grafting. The entry tear was located at the ascending aorta in 10 cases (DeBakey type I), the aortic arch in 14 cases and the distal aortic arch or proximal descending aorta in 21 cases in which the ascending aorta was also involved by the dissection. The surgical success rate was 97.8% (44/45) and 30-day mortality rate was 6.7% (3/45). Type I endoleaks occurred in 10 cases: one patient died intra-operatively, four were successfully treated with ballooning, four were sealed with aortic cuffs and one case caused by left subclavian artery (LSA) reflux was sealed with an occluder. Average follow-up time was 35.5 ± 5.4 months. Up to the most recent review or death, 32 patients had complete thrombosis and 10 had partial thrombosis inside the false lumen. Two deaths occurred after 30-days postoperatively. Endovascular stent-graft treatment is a minimally invasive and effective method to treat Stanford type A aortic dissection.


The prevalence and risk indicators of tooth wear in 12- and 15-year-old adolescents in Central China.
Tooth wear has been investigated in numerous countries, and the prevalence has varied. However, the data on tooth wear in China are scarce. The aim of this study was to describe the prevalence of tooth wear and to investigate the relative indicators associated with tooth wear in 12- and 15-year-old adolescents in Wuhan City, Hubei Province, Central China. A cross-sectional descriptive study was undertaken among 720 adolescents in Hubei Province, Central China. The age groups in this study were 12- and 15-year-old, and each group consisted of 360 participants in which females and males represented 50 % each. A modified version of the Basic Erosive Wear Examination (BEWE) tooth wear index was used for the buccal, cervical, occlusal/incisal and lingual surfaces of all of the teeth in the 720 adolescents. All of the participants were asked to answer a questionnaire consisting of questions about their current and historical dietary habits and oral hygiene. The prevalence of tooth wear was 18.6 and 89.4 % in 12- and 15-year-old adolescents, respectively. The prevalence rates of dentin exposure were 1.9 and 5.6 %, respectively. A significantly higher prevalence of tooth wear and dentin exposure in 15-year-old adolescents was found than in 12-year-old adolescents (p < 0.001 and p = 0.011). Several factors such as drinking soft drinks and fruit juices immediately after sports, taking aspirin, reflux, unilateral chewing, tooth brushing once daily or less often, duration of brushing less than 2 min and swimming in the summer were found to be associated with tooth wear. Tooth wear in 12- and 15-year-old adolescents in Central China is a significant problem and should receive greater attention. The prevalence of tooth wear increases with age and associated with socio-behavioral risk factors.


HnRNPL as a key factor in spermatogenesis: Lesson from functional proteomic studies of azoospermia patients with sertoli cell only syndrome.
Sertoli cell only syndrome (SCOS) is one of the main causes leading to the abnormal spermatogenesis. However, the mechanisms for abnormal spermatogenesis in SCOS are still unclear. Here, we analyzed the clinical testis samples of SCOS patients by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to find the key factors contributing to SCOS. Thirteen differential proteins were identified in clinical testis samples between normal spermatogenesis group and SCOS group. Interestingly, in these differential proteins, Heterogeneous nuclear ribonucleoprotein L(HnRNPL) was suggested as a key regulator involved in apoptosis, death and growth of spermatogenic cells by String and Pubgene bioinformatic programs. Down-regulated HnRNPL in testis samples of SCOS patients was further confirmed by immunohistochemical staining and western blotting. Moreover, in vitro and in vivo experiments demonstrated that knockdown of HnRNPL led to inhibited proliferation, increased apoptosis of spermatogenic cell but decreased apoptosis of sertoli cells. Expression of carcinoembryonic antigen-related cell adhesion molecule 1 in GC-1 cells or expression of inducible nitric oxide synthases in TM4 sertoli cells, was found to be regulated by HnRNPL. Our study first shows HnRNPL as a key factor involved in the spermatogenesis by functional proteomic studies of azoospermia patients with sertoli cell only syndrome. This article is part of a Special Issue entitled: Proteomics: The clinical link.


Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid.
Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 microM, respectively), though with activities considerably lower than Ibo (EC50 = 9.6 microM). N-Benzyl-Ibo (1c) was inactive at ionotropic EAA receptors and all three compounds were, in contrast to Ibo, inactive at metabotropic EAA receptors. Molecular mechanics calculations have been performed on Ibo, 1a-c and the potent NMDA agonist 2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA) in order to elucidate the observed structure-activity data.


Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL.
The critical function of microRNAs in the pathogenesis and prognosis of hematopoietic cancer has become increasingly apparent. However, only a few miRNAs have been reported to be altered in acute lymphocytic leukemia (ALL). To uncover aberrantly expressed miRNAs in pediatric B-cell ALL, our study employed genome-wide miRNA microarray analysis and stem-loop real-time quantitative polymerase chain reaction (qRT-PCR) to examine common precursor B-cell ALL samples. The target genes of miRNA-708 were then identified and verified by bioinformatics, dual-luciferase reporter assay, qRT-PCR, and Western blot. Significant upregulation of miR-708, miR-210, and miR-181b, and downregulation of miR-345 and miR-27a were observed in common precursor B-cell ALL (common-ALL) samples (P < 0.05). In addition, elevated expression of miR-708 and miR-181b were found in high-risk common-ALL compared to standard and intermediate ones. miR-708 inhibited luciferase reporter activity by binding to the 3'-untranslated regions (3'-UTRs) of CNTFR, NNAT, and GNG12 mRNA in HEK-293 cell line and suppressed the protein levels of CNTFR, NNAT, and GNG12 in Jurkat cells. In addition, mRNA levels of CNTFR and NNAT, but not of GNG12, were found to be downregulated in high risk common-ALL samples. Mutational analysis revealed that miR-708 binds to the 394-400 bp sequence region of the 3'-UTR of CNTFR mRNA. The expression level of miR-708 reflects differences among the clinical types of common-ALL, and CNTFR, NNAT, and GNG12 were identified as targets of miR-708.


Using the Pelvic Floor Impact Questionnaire to Improve Urinary Incontinence Assessments for Female Veterans.
To evaluate quality of life (QoL) in female veterans by comparing responses of the Pelvic Floor Impact Questionnaire (PFIQ-7) before and after a chosen treatment for urinary incontinence (UI), determine whether a QoL assessment was being completed for each woman seeking care for UI, and review the PFIQ-7 questionnaire scores to ensure the veterans were offered the appropriate levels of treatment. Quality improvement project using the plan-do-study-act cycle for evaluating change. A Veterans Affairs Medical Center in the midwestern United States. No standardized education or QoL questionnaire was being used for female veterans diagnosed with UI before implementation of the project. Twenty female veterans diagnosed with stress or mixed UI who had completed Kegel exercises or pelvic floor rehabilitation (PFR) and a pre- and posttreatment PFIQ-7. The Veterans Affairs Medical Center incorporated the PFIQ-7 into routine practice for pre- and posttreatment assessment of UI. Data were collected through a retrospective chart review. The mean initial PFIQ-7 score for participants (n = 4) who chose PFR was 71.77 (SD = 82.79). The mean final PFIQ-7 score for participants in the PFR group was 43.99 (SD = 63.34). The mean initial PFIQ-7 score for participants who chose Kegel exercises was 71.72 (SD = 34.92), and the final score was 60.71 (SD = 44.98). When comparing pre- and posttreatment scores, a lower score means there was a positive effect from the treatment and reflects an improved QoL. The addition of the QoL assessment tool assisted staff in developing an individualized plan of care for female veterans. Regardless of treatment option chosen, participants who did not show an overall improvement in the pre- and posttreatment QoL scores were referred to a more advanced level of care.


Relationship Between Performance Improvement in Activities of Daily Living and Energy Intake in Older Patients With Hip Fracture Undergoing Rehabilitation.
To analyze whether sufficient energy intake (EI) improves performance of activities of daily living (ADL) in patients with hip fracture admitted to rehabilitation hospitals. The adequate amount of EI for improving performance of ADL in patients with hip fracture remains unknown. This retrospective cohort study included all patients with hip fracture (n=234) admitted to rehabilitation hospitals in Japan. The inclusion criteria for this study were age >65 years and body mass index <30.0 kg/m2. Patients who were transferred to an acute hospital and those with missing case data were excluded. According to the amount of EI, the patients were classified into energy sufficiency and shortage groups (EI/total energy expenditure ≥1.0 and <1.0, respectively). The Functional Independence Measure (FIM) and FIM gain were used to evaluate the patient disability level and change in patient status in response to rehabilitation. Finally, FIM gain was calculated as the discharge FIM score minus the admission FIM score. The final analysis targeted 202 patients-53 (26.2%) were in the energy shortage group and 149 (73.8%) were in the energy sufficiency group. The energy sufficiency group had a greater FIM gain than the energy shortage group (mean, 25.1±14.2 vs. 19.7±16.4; p=0.024). Furthermore, sufficient EI in the first week since admission (β=0.165; 95% confidence interval, 0.392-5.230; p=0.023) was an independent factor of FIM gain. Among elderly patients with hip fracture admitted to rehabilitation hospitals in Japan, the amount of EI during the first week after admission was an independent factor of FIM gain.


Toxicological study of plant extracts on termite and laboratory animals.
Toxic activity of leaf extracts of Polygonum hydropiper L. and Pogostemon parviflorus Benth. were tested in the laboratory against tea termite, Odontotermes assamensis Holm. Both the tested extracts caused mortality of the termite. The highest toxic activity (100%) was found in the 2.0% chloroform extracts of P. hydropiper. The chloroform extract of P. hydropiper was explored for possible mammalian toxicological effects. The LD50 was 758.58 mg/kg in male albino mice. Subcutaneous injection of sub-lethal dose of extract into male mice once a week for 6 weeks failed to express any significant influence on WBC, RBC count and blood cholesterol.


Cerebral proliferative angiopathy with papilledema.
A young female presented with intermittent blurring of vision and mild to moderate headache for three months. Fundus examination revealed bilateral papilledema with secondary optic atrophy (right more than left). Computed tomography scan of brain showed a diffuse intraparenchymal vascular malformation in right parietooccipital region. Cerebral digital subtraction angiography (DSA) revealed diffuse nidus in right parietooccipital area, supplied by multiple branches of distal middle cerebral artery and anterior cerebral artery. Scattered-puddling appearance of contrast was noted in diffuse nidus and there were no definite arterial feeders. DSA was consistent with the diagnosis of cerebral proliferative angiopathy (CPA). The patient was started on acetazolamide 250 mg twice a day. At six months follow up, she was asymptomatic with resolving papilledema. CPA is a rare vascular malformation, any case report that gives further insight to it will be very useful to the scientific community. Herein, we describe an unusual association of CPA with papilledema.


Penehyclidine hydrochloride ameliorates renal ischemia-reperfusion injury in rats.
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney failure by mechanisms that involve oxidative stress, inflammation, and apoptosis. Penehyclidine hydrochloride (PHC), a selective anticholinergic agent, possesses anti-inflammatory, antioxidative stress, and antiapoptotic effects. Therefore, we investigated the ability of PHC to ameliorate renal I/R injury in Sprague-Dawley rats. Rats were randomly assigned to three groups (35 rats per group): sham operated, saline-treated I/R, and PHC-treated I/R. After removing the right kidney, renal I/R injury was induced by clamping the left renal artery for 45 min followed by reperfusion. The rats were administered PHC (0.45 mg/kg, intravenously) or saline 30 min before renal ischemia. The blood and kidneys were harvested at 1, 3, 6, 12, or 24 h after reperfusion. Renal function and histologic changes were assessed. Markers of oxidative stress, inflammation, and apoptosis in the kidneys were also measured. PHC treatment significantly attenuated renal dysfunction and histologic damage caused by I/R injury. The treatment also decreased malondialdehyde level and attenuated the reduction in superoxide dismutase activity in the kidney. Moreover, the levels of activated p38 mitogen-activated protein kinase, nuclear factor kappa B, and caspase 3 were lower in the PHC-treated animals. PHC protected rat kidneys from I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis. Thus, PHC may represent a novel practical strategy for the treatment of renal I/R injury.


Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis.
To assess the efficacy of diethylcarbamazine (DEC) in clearing Wuchereria bancrofti microfilariae (mf) from the circulation, we conducted a single blind hospital-based therapeutic trial of 3 DEC regimens. All patients were assessed by filtration of 1 mL of venous blood taken before and 1, 3, 6 and 12 months after DEC administration. The efficacy of a 12 d course of 6 mg/kg DEC once daily was identical to that of a similar course with 2 mg/kg given 3 times daily, indicating that split-dose treatment does not improve mf clearance over single daily drug administration. Microfilarial densities in patients treated only once with 6 mg/kg DEC remained significantly higher at 1, 3, and 6 months after treatment. However, all 3 treatment regimens proved equally effective in controlling microfilaraemia after 12 months, when 41, 42 and 40% of patients in the 3 treatment groups were amicrofilaraemic. These results suggest that a single DEC dose of 6 mg/kg administered annually or biannually may be a suitable regimen to control bancroftian filariasis in Recife, Brazil.


Tissue-specific ablation of Prkar1a causes schwannomas by suppressing neurofibromatosis protein production.
Signaling events leading to Schwann cell tumor initiation have been extensively characterized in the context of neurofibromatosis (NF). Similar tumors are also observed in patients with the endocrine neoplasia syndrome Carney complex, which results from inactivating mutations in PRKAR1A. Loss of PRKAR1A causes enhanced protein kinase A activity, although the pathways leading to tumorigenesis are not well characterized. Tissue-specific ablation of Prkar1a in neural crest precursor cells (TEC3KO mice) causes schwannomas with nearly 80% penetrance by 10 months. These heterogeneous neoplasms were clinically characterized as genetically engineered mouse schwannomas, grades II and III. At the molecular level, analysis of the tumors revealed almost complete loss of both NF proteins, despite the fact that transcript levels were increased, implying posttranscriptional regulation. Although Erk and Akt signaling are typically enhanced in NF-associated tumors, we observed no activation of either of these pathways in TEC3KO tumors. Furthermore, the small G proteins Ras, Rac1, and RhoA are all known to be involved with NF signaling. In TEC3KO tumors, all three molecules showed modest increases in total protein, but only Rac1 showed significant activation. These data suggest that dysregulated protein kinase A activation causes tumorigenesis through pathways that overlap but are distinct from those described in NF tumorigenesis.


[Intensive care in rabies. A case report (author's transl)].
A case of human rabies is reported showing a peculiar course in some respects. The lack of a satisfactory history concerning an animal bite 5 months earlier as well as a misleading psychiatric history led to difficulty and delay in reaching a diagnosis. Under intensive care, including mechanical ventilation and cardiac pacing, the disease reached a final stage, which is rarely seen. The clinical course and the pathological findings are described in detail and the etiology and prognosis of the disease are discussed. The latter remains rather hopeless de spite modern intensive care.


DNA Methylation Signatures of Multiple Sclerosis Occur Independently of Known Genetic Risk and Are Primarily Attributed to B Cells and Monocytes.
Epigenetic mechanisms can regulate how DNA is expressed independently of sequence and are known to be associated with various diseases. Among those epigenetic mechanisms, DNA methylation (DNAm) is influenced by genotype and the environment, making it an important molecular interface for studying disease etiology and progression. In this study, we examined the whole blood DNA methylation profiles of a large group of people with (pw) multiple sclerosis (MS) compared to those of controls. We reveal that methylation differences in pwMS occur independently of known genetic risk loci and show that they more strongly differentiate disease (AUC = 0.85, 95% CI 0.82-0.89, p = 1.22 × 10-29) than known genetic risk loci (AUC = 0.72, 95% CI: 0.66-0.76, p = 9.07 × 10-17). We also show that methylation differences in MS occur predominantly in B cells and monocytes and indicate the involvement of cell-specific biological pathways. Overall, this study comprehensively characterizes the immune cell-specific epigenetic architecture of MS.


Changes in population, growth, and physiological indices of Longnose dace (Rhinichthys cataractae) in the Red Deer River, Alberta, Canada.
The Red Deer River, Alberta, Canada is a prairie river that is impacted by the point-source input of Red Deer's municipal wastewater effluent and non-point- source agricultural runoff. We used population, growth, and physiological performance end points in longnose dace (Rhinichthys cataractae), an endemic and abundant minnow, to evaluate changes in fish health over a 220 km section of the Red Deer River. Longnose dace immediately downstream of Red Deer had elevated catch per unit effort with larger body and liver sizes compared to upstream of Red Deer sites, likely due to elevated riverine productivity from Red Deer's wastewater effluent. Longnose dace immediately downstream of Red Deer showed depressed testosterone production capacity and elevated ethoxyresorufin-O-deethylase (EROD) activity, which is consistent with exposure to endocrine-disrupting compounds and aromatic hydrocarbons, respectively. Longnose dace 150-180 km downstream of Red Deer had reduced liver and gonad sizes, elevated EROD, and increased 11-ketotestosterone production capacity compared to upstream of Red Deer sites, possibly related to a non-point-source agricultural influence on water quality. Longnose dace populations at the most downstream sites were missing the oldest age classes and might reach sexual maturity faster than at upstream sites, which is consistent with a younger age structure. Our results highlight the importance of assessing multiple performance end points to reveal physiological or reproductive effects in natural fish populations. We have demonstrated how longnose dace populations change over a river impacted by municipal wastewater and agricultural runoff; further studies are required to determine if these changes will influence the long-term viability of longnose dace in the Red Deer River.


Capsaicin-induced stimulation of the guinea-pig atrium. Involvement of a novel sensory transmitter or a direct action on myocytes?
The mechanism underlying the positive inotropic and chronotropic effects of capsaicin were investigated using the spontaneously beating guinea-pig atrium in vitro. Capsaicin induced a long-lasting stimulatory effect (threshold dose 10(-9) M). Tetrodotoxin, phentolamine, 6-OHDA, mepyramine plus cimetidine, methysergide-, indomethacin-, somatostatin- or morphine pretreatment and local treatment with capsaicin on the vagal nerves did not reduce the capsaicin response, while it was abolished up to 1 month after systemic capsaicin pretreatment. The capsaicin response was subject to a rapid tachyphylaxis. During capsaicin tachyphylaxis, the positive inotropic and chronotropic effects of noradrenaline, serotonin and histamine were unchanged. Various neuropeptides were investigated with regard to cardiac activity. Physalaemin, eledoisin and somatostatin had negative inotropic and chronotropic effects. Substance P, bombesin, kassinin, CCK-8 or PHI (up to 10(-6)M of each) did not cause any detectable response on the guinea-pig auricle, while the substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]SP induced a long-lasting stimulation of heart activity, VIP also stimulated the heart. Various adenyl compounds were also tested. Adenosine, AMP, ADP, ATP and beta-, gamma-methylene ATP had negative chronotropic and inotropic effects, while alpha-, beta-methylene ATP induced a stimulatory response. During alpha-, beta-methylene ATP tachyphylaxis, the auricles still responded to capsaicin. The inhibitory effects of adenosine and ATP analogues were antagonized by theophylline and 8-p-sulfophenyl theophylline. Capsaicin induced a small release of labelled nucleotides from 3(H)-adenine-prelabelled atria from control, but not from capsaicin-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Favorable effects of Anethum graveolens on liver oxidative stress and cholesterol 7 alpha-hydroxylase levels in non-alcoholic fatty liver disease (NAFLD) rat models.
High-fat high-cholesterol diet induces a phenotype similar to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in humans. In NAFLD and NASH, cholesterol and bile acid metabolisms are impaired to accumulate lipids and toxic bile acids along with cholestatic hepatic damage. Recently, the use of herbal-derived cholesterol lowering products has attracted much attention as possible therapeutic strategies for NAFLD. Hence, the aim of this study was to determine the effects of an Anethum graveolens (dill) on liver cholesterol 7 alpha-hydroxylase and liver fat accumulation in rats. Thirty-six rats were randomly divided into 6 groups (n = 6) and received normal diet (ND) or a mixture of chow diet+2% cholesterol+0.5% cholic acid + 20% corn oil as high cholesterol/fat (HC-HF) diet (NAFLD model). Animals were also treated daily with dill tablet or dill extract (300 mg/kg). At the end of the 30 days experiments, serum and liver lipid profile and liver total antioxidant capacity were determined. Cholesterol 7 alpha-hydroxylase mRNA and protein expression levels were determined in the liver and histopathological changes in liver tissues were analyzed by microscope. Lipid profiles significantly decreased in dill treated groups (p < 0.05). Liver total antioxidant capacity significantly (p < 0.05) increased and MDA levels markedly (p < 0.05) reduced both in dill tablet and dill extract treated groups (p < 0.05). Both types of treatments caused significant increases in liver cholesterol 7 alpha-hydroxylase gene expression (p < 0.05). Histopathological examinations showed that treatment with dill normalized the hypercholesterolemia-induced changes in liver histology. Administration of dill significantly reduced liver fat, oxidative stress and increased cholesterol 7 alpha-hydroxylase enzyme at the both mRNA and protein levels. Dill extract was found more effective than its commercially available tablet.


Pericarditis.
Pericarditis is a common disorder that has multiple causes and presents in various primary-care and secondary-care settings. New diagnostic techniques have improved the sampling and analysis of pericardial fluid and allow comprehensive characterisation of cause. Despite this advance, pericarditis is most commonly idiopathic, and radiation therapy, cardiac surgery, and percutaneous procedures have become important causes. Pericarditis is frequently self-limiting, and non-steroidal anti-inflammatory agents remain the first-line treatment for uncomplicated cases. Integrated use of new imaging methods facilitates accurate detection and management of complications such as pericardial effusion or constriction. Differentiation of constrictive pericarditis from restrictive cardiomyopathy remains a clinical challenge but is facilitated by tissue doppler and colour M-mode echocardiography. Most pericardial effusions can be safely managed with an echo-guided percutaneous approach. Pericardiectomy remains the definitive treatment for constrictive pericarditis and provides symptomatic relief in most cases. In the future, the pericardial space might become a conduit for treatments directed at the pericardium and myocardium.


Individualized treatment for iron-deficiency anemia in adults.
Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption. Iron-deficiency anemia remains prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron-deficiency anemia are discussed with emphasis placed on consideration of patient-specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based on the tolerated daily dose and the total iron deficit. Each cycle consists of 5000 mg of oral elemental iron ingested over at least 1 month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron-deficiency anemia.


Expression and significance of PTEN and VEGF in canine mammary gland tumours.
To investigate the relationship between the expression of the PTEN (phosphatase and tensin homolog deleted on chromosometen) and VEGF (vascular endothelial growth factor) and the clinicopathological features in canine mammary gland tumours, the expression levels of PTEN and VEGF protein were assessed in 50 cases of canine mammary gland tumours tissues and 4 cases of normal mammary gland tissues with using immunohistochemical method. The over-expression rate of PTEN protein was 100% in normal and well-differentiated mammary gland tissues and 67% in breast cancer cases respectively with a significant difference between the two groups (P<0.01). Expression of PTEN was not related to age and tumour size, but closely correlated to lymph node metastasis (P<0.01). The over-expression rate of VEGF protein was 33.3% in normal mammary gland tissues, and 78% in canine mammary gland tumours with a significant difference between the two groups (P<0.01). Expression of VEGF was not related to age or tumour size, but closely correlated with lymph node metastasis and clinical stage (P<0.05). Therefore the combination detection of PTEN and VEGF could serve as an important index to estimate the biological behavior and prognosis of canine mammary gland tumours. Reduced expression of PTEN might be involved in carcinogenesis and progression of canine breast cancer by up-regulating the VEGF expression to enhance angiogenesis.


HIV prevalence among 338,432 infertile individuals in Hunan, China, 2012-2018: A cross-sectional study.
The prevalence of human immunodeficiency virus (HIV) varies markedly among different risk groups in China, spreading fromhigh-risk populations to the general population. Indeed, China is in a critical period of HIV/acquired immunodeficiency syndrome (AIDS) prevention and control; however, data regarding HIV testing, infection and coinfection among infertile couples are lacking. This study aimed to estimate the HIV/AIDS prevalence to identify risk factors among infertile couples in Hunan, China. A cross-sectional hospital-based study was conducted to evaluate the prevalence of HIV/other infections (hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium (MG) infections) among 338,432 infertile individuals in Hunan, China, from 2012 to 2018. We calculated linear trends in prevalence using bivariate linear regression. The overall prevalence rates of HIV, chlamydia, gonorrhea, MG, syphilis, and HBV and HCV antibody positivity in this study were 0.04%, 1.73%, 0.05%, 2.60%, 2.15%, 12.01% and 0.56%, respectively. The predominant infection was HBV, followed by MG, syphilis, and chlamydia. Only 1.13% of the participants (382/338432) reported sexually transmitted disease (STD) signs and symptoms suggesting genital tract infection. However, from 2012-2018, the variation in HIV prevalence was not significant (β = 0.000, PTREND = 0.907). The characteristics of the HIV-infected infertile population have not shifted dramatically, with women accounting for 32.56% of HIV cases in China. Overall, 87.60% of HIV-infected individuals have a relatively low education. In total, 37.98% of HIV-positive patients engage in high-risk behaviors. This study expands upon existing knowledge of HIV prevalence in the infertile Chinese population. However, much work is needed to achieve popularization of prevention knowledge and change concept. Routine HIV screening is urgently needed for all adults with high-risk behaviors.


Role reversal: the regulation of neuronal gene expression by microRNAs.
In a similar fashion to transcription factors, non-coding RNAs can be essential regulators of gene expression. The largest class of non-coding RNAs is the microRNAs. These approximately 22 nt double-stranded RNA molecules can repress translation or target mRNA degradation. There has been a surge of research in the past year stimulated by the recent availability of specialized techniques, both in vitro and in silico, for predicting and characterizing microRNAs. The accumulating evidence suggests that microRNAs are ubiquitous regulators of gene expression during development. The combined actions of microRNAs and transcription factors are able to tune the expression of proteins on a global level in a manner that cannot be achieved by transcription factors alone.


Helicobacter spp. in Experimental Models of Colitis.
The colonization of body surfaces, notably of the intestine, by a complex microbiota is generally highly mutualistic, where vital functions are provided by the commensal microbiota to the host, including the synthesis of vitamins, the degradation of complex polysaccharides into small chain fatty acids (which are essential for the maintenance of the intestinal epithelial barrier), and, finally, the outcompetition of pathogens that accidentally gain access to the body ("colonization resistance") (Chow et al. 2011; Backhed 2005). However, under certain conditions, such as changes of environmental factors in a genetically predisposed host, some of these normally symbiotic bacteria may act as pathogens and induce pathologies. Hence, the term "pathobionts" was coined for these bacterial species with ambiguous biological properties (Round et al. 2009).


Pericentromeric euchromatin is conserved in minute human supernumerary chromosomes: a study using cross-species colour segmenting (RxFISH).
Investigation of marker chromosomes is one of the most challenging areas of clinical cytogenetics, especially in the prenatal scenario. A range of techniques including microdissection/reverse painting, SKY and M-FISH are available for the investigation of larger markers (>3 Mb). All these techniques rely on hybridization of unique, homologous sequences with simultaneous suppression of repeat sequences. In contrast, RxFISH is based on hybridization of cross-species syntenic sequences; repeat sequences do not hybridize due to species divergence. We have used RxFISH to analyse a group of the smallest, i.e. minute, supernumerary marker chromosomes. Our results suggest that even the smallest marker chromosomes often contain conserved pericentric euchromatin. More detailed characterization of pericentric genetic content is needed to assess the clinical significance of minute supernumerary markers.


A mutation of pyruvate carboxylase in fibroblasts from a patient with severe, chronic lactic acidaemia.
Pyruvate carboxylase activity was investigated in cultured fibroblasts from a patient shown to have hepatic pyruvate carboxylase deficiency. Under standard conditions, the activity in fibroblasts was 50% of controls (p less than 0.001). Kinetic investigations of the enzyme showed abnormal protein linearity with low activity at low protein concentration. Mixture of homogenates from the patient and a control revealed no endogenous inhibitor. Temperature stability of the mutant enzyme was similar to controls. Apparent kinetic constants for the substrates bicarbonate, ATP and pyruvate were in the patient 2.6 mmol/l, 0.08 mmol/l and 0.10 mmol/l compared to 2.1 mmol/l, 0.13 mmol/l and 0.22 mmol/l in controls, respectively. The 50% inhibitory concentration of oxaloacetate was 0.5 mmol/l in controls. However, no inhibitory effect of oxaloacetate was found for pyruvate carboxylase in fibroblasts from the patient. With acetyl-CoA, the apparent activation constant was 0.21 mmol/l in controls and 0.10 mmol/l in the patient, while the Hill coefficients were similar. These results may be explained by a mutation primarily affecting the transcarboxylation site of pyruvate carboxylase from the patient.


Environmental stress increases extracellular dopamine in striatum of 6-hydroxydopamine-treated rats: in vivo microdialysis studies.
Bilateral intraventricular injections of 6-hydroxydopamine depleted dopamine (DA) in striatal tissue of rats by 88%. Tail shock increased DA in striatal extracellular fluid of these rats from 10 to 17 pg/20 microliters as measured by microdialysis, values less than half those seen in normal striatum. The increase was observed even in rats that were akinetic. DA in extracellular fluid after stress was negatively correlated with behavioral performance. Thus, residual nigrostriatal DA neurons are responsive to stress but do not produce normal DA levels in striatal extracellular fluid.


Integrated health service delivery networks and tuberculosis avoidable hospitalizations: is there a relation between them in Brazil?
The early identification of the Breathing Symptoms within the scope of Primary Health Care is recommended, and is also one of the strategies of national sanitary authorities for reaching the elimination of tuberculosis. The purpose of this study is to consider which attributes and which territories have shown the most significant progress in Primary Health Care, in terms of coordination of Health Care Networks, and also check if those areas of Primary Health Care that are most critical regarding coordination, there were more or less cases of avoidable hospitalizations for tuberculosis. This is an ecological study that uses primary and secondary data. For analysis, coropletic maps were developed through the ArcGIS software, version 10.2. There was also the calculation of gross annual and Bayesian rates for hospitalizations for tuberculosis, for each Primary Health Care territory. There were satisfactory results for attributes such as Population (n = 37; 80.4 %), Primary Health Care (n = 43; 93.5 %), Support System (n = 45; 97.8 %); the exceptions were Logistics System (n = 32; 76.0 %) and Governance System, with fewer units in good condition (n = 31; 67.3 %). There is no evidence of any connection between networks' coordination by Primary Health Care and tuberculosis avoidable admissions. The results show that progress has been made regarding the coordination of the Health Care Networks, and a positive trend has been shown, even though the levels are not excellent. It was found no relationship between the critical areas of Primary Health Care and tuberculosis avoidable hospitalizations, possibly because other variables necessary to comprehend the phenomena.


The Zellweger syndrome: deficient chain-shortening of erucic acid (22:1 (n-9)) and adrenic acid (22:4 (n-6)) in cultured skin fibroblasts.
In the Zellweger syndrome where peroxisomes are absent, extremely long fatty acids (24:0 and 26:0) accumulate in tissues suggesting that these fatty acids are normally beta-oxidized in the peroxisomes. Previous studies with rat hepatocytes suggest that peroxisomes are also important in oxidation of C22 unsaturated fatty acids. This study shows that cultured fibroblasts from normal human controls shorten [14-14C]erucic acid (22:1(n-9)) to oleic acid (18:1(n-9)) efficiently while Zellweger fibroblasts are deficient in chain-shortening. [2-14C]Adrenic acid (22:4(n-6)) is oxidized in control fibroblasts probably by chain-shortening to arachidonic acid (20:4(n-6)). Only a little adrenic acid is oxidized in Zellweger fibroblasts. Linolenic acid (18:3(n-3)) is desaturated and chain-elongated in both control and Zellweger fibroblasts. The results support the view that peroxisomes play a normal physiological role in the shortening of C22 unsaturated fatty acids and that this function is deficient in Zellweger fibroblasts.


Home visiting nurses' attitudes toward caring for dying patients, and related workplace factors.
To identify workplace factors related to home visiting nurses (HVNs) positive attitudes toward caring for dying patients. In this cross-sectional study, 343 HVNs working in 62 agencies across Chiba prefecture, eastern Japan, received an anonymous self-administered questionnaire from July to August 2012. 304 questionnaires (88.6%) were returned, and the data of 206 HVNs (60.1%) in 54 different agencies was analysed. Multiple regression analysis showed that attendance at terminal care seminars, agency support of schedule organisation enabling attendance at terminal care seminars, and positive feedback from patients and families were significantly positively associated with HVNs' attitudes toward terminal care. These results may give useful interventional methods for nursing managers to enhance HVNs terminal care practices.


The anatomical evaluation of the dental arches using cone beam computed tomography--an investigation of the availability of bone for placement of mini-screws.
To assess the amount of maxillary and mandibular inter-radicular bone mass and determine the most reliable mini-screw placement sites. Retrospective Cone Beam Computed Tomography (CBCT) images of 40 Angle Class I subjects (20 females, 20 males, aged 16 to 32) were obtained. Measurements on the buccal (BI), medial (MI) and lingual (LI) sides of the inter-radicular spaces were taken at 0, 1, 2, 3, 4, 5 mm from the cemento-enamel junction (CEJ) in an apical direction. The male and female BI scores ranged from 2.99±0.73 mm to 6.18±1.03 mm and 2.69±0.84 mm to 6.21±1.22 mm respectively. The male and female MI scores ranged from 1.36±0.38 mm to 4.50±0.99 and 1.53±0.66 to 4.77±1.99 mm respectively. LI scores ranged from 2.37±0.70 to 6.47±1.0 mm and 2.45±0.56 mm and 6.66±1.33 mm respectively. In both maxillary and mandibular arch, the inter-radicular space increased in the apical direction except for the buccal and medial inter-radicular spaces between the maxillary first and second molars. The medial inter-radicular spaces are the decisive parameter for mini-screw placement. In the maxillary arch, regions between central and lateral incisors, lateral incisor and canine, first and second molars are not viable for mini-screw insertion. The residual inter-radicular regions are proper for implantation at 3 mm above the CEJ. In the mandible, the regions between incisors and canines are too narrow for mini-screw insertion and the reliable sites for mini-screws are regions between premolars, molars or first molar and second premolar at 2 mm below the CEJ.


Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome.
Cardiovascular mortality is increased in rheumatoid arthritis. Possible reasons include an increased incidence of ischaemic heart disease or worse outcome after acute coronary syndrome (ACS). To assess the outcome of ACS in rheumatoid arthritis compared with case matched controls in the context of underlying cardiac risk factors, clinical presentation, and subsequent management. 40 patients with rheumatoid arthritis and ACS identified from coronary care admission registers between 1990 and 2000 were case matched as closely as possible for age, sex, classical cardiovascular risk factors, type and severity of ACS, and admission date (+/-3 months) with 40 controls. A standardised proforma was used for detailed case note review. Age, sex, other cardiovascular risk factors, and type and severity of presenting ACS were not significantly different between cases and controls. Recurrent cardiac events were commoner in rheumatoid arthritis (23/40, 57.5%) than controls (12/40, 30%) (p = 0.013); there were 16/40 deaths in rheumatoid arthritis (40%) v 6/40 (15%) in controls (p = 0.012). Recurrent events occurred earlier in rheumatoid arthritis (log rank survival, p = 0.05). Presentation with chest pain occurred in all controls compared with 33/40 rheumatoid patients (82%) (p = 0.006); collapse occurred in one control (2.5%) v 7/40 rheumatoid patients (17.5%) (p = 0.025). Treatment during the ACS was not significantly different in the two groups. Recurrent ischaemic events and death occur more often after ACS in rheumatoid arthritis. Atypical presentation is commoner in rheumatoid arthritis. There is an urgent need to develop identification and intervention strategies for ACS specific to this high risk group.


Interfacial plasticity facilitates high reaction rate of E. coli FAS malonyl-CoA:ACP transacylase, FabD.
Fatty acid synthases (FASs) and polyketide synthases (PKSs) iteratively elongate and often reduce two-carbon ketide units in de novo fatty acid and polyketide biosynthesis. Cycles of chain extensions in FAS and PKS are initiated by an acyltransferase (AT), which loads monomer units onto acyl carrier proteins (ACPs), small, flexible proteins that shuttle covalently linked intermediates between catalytic partners. Formation of productive ACP-AT interactions is required for catalysis and specificity within primary and secondary FAS and PKS pathways. Here, we use the Escherichia coli FAS AT, FabD, and its cognate ACP, AcpP, to interrogate type II FAS ACP-AT interactions. We utilize a covalent crosslinking probe to trap transient interactions between AcpP and FabD to elucidate the X-ray crystal structure of a type II ACP-AT complex. Our structural data are supported using a combination of mutational, crosslinking, and kinetic analyses, and long-timescale molecular dynamics (MD) simulations. Together, these complementary approaches reveal key catalytic features of FAS ACP-AT interactions. These mechanistic inferences suggest that AcpP adopts multiple, productive conformations at the AT binding interface, allowing the complex to sustain high transacylation rates. Furthermore, MD simulations support rigid body subdomain motions within the FabD structure that may play a key role in AT activity and substrate selectivity.


[The thalamic integration of afferent flows in man during image recognition].
The article deals with the mechanisms of interaction of afferent flows at intrathalamic and thalamocortical levels of integration in humans identifying visual, auditory and tactile images. As the methodic model of thalamic block we used patients of surgical clinic with topically diagnosed volume process of the region of the third ventricle. Psychophysiological tests and multichannel EPs recording revealed functional significance of thalamus in the processes of perception and also mechanisms of compensation of these functions in pathological process.


Knowledge, attitude, and practice among healthcare workers towards COVID-19 outbreak in Nigeria.
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is a global pandemic. Healthcare workers' (HCWs) role in patient management is predisposing and can serve as means of hospitals and community transmission. This study evaluated HCWs' knowledge, attitude, and practice towards COVID-19 in Nigeria. we carried out a cross-sectional survey among HCWs during the COVID-19 outbreak in Nigeria from March to June 2020. The study assessed 346 HCWs for Knowledge, attitude, and practice by using an online (Google form) self-administered questionnaire, based on a convinience sampling technique Data were retrieved and analyzed using descriptive statistics. Chi-Square and one-way ANOVA were used to measure association and difference among demographic variables. The relationship between knowledge, attitude, and practice was measured using Spearman's rho correlation test. the mean knowledge score of the HCWs was 7.1 on a scale of 0-8. The correct overall rate of the knowledge questionnaire was 88.75%. Knowledge was gained mainly from television (35.0%) and social media (35.0%). The mean attitude score on a scale of 0-6 was 5.31 ± 0.39. Most (92.5%) participants were confident that Nigerian medical scientists would win the war against COVID-19. The majority (92.2%) of the respondents thought that SARS-CoV-2 was not a biological weapon. About 1 out of 5 respondents held that faith healing or prayer is the only cure for COVID-19. A vast majority of the HCWs were taking precautionary measures such as avoiding crowded places (94.2%), washing of hands (96.0%), and the use of personal protective equipment (91.6%) against SARS-CoV-2 infection. Nevertheless, only 3 out of 5 HCWs used a face mask when leaving home. There was a significant (p = 0.046) positive correlation (0.584) between knowledge and attitude. our results showed that HCWs in Nigeria had excellent knowledge and possessed a positive attitude and good practice towards COVID-19. However; there were areas where poor knowledge, negative attitudes and unacceptable practices were observed. We recommend continuous public health education of HCWs on SARS-COV-2 infection control and prevention.


Study of nonspecific lymphocyte transformation in urologic cancer patients.
Blast-cell transformation of lymphocytes in response to phytohaemagglutinin was examined in patients with urologic tumours and with nonmalignant urologic processes. A significant depression of immune reactivity was found in the malignant cases. The practical aspects of the findings are discussed.


A murine model of targeted infusion for intracranial tumors.
Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.


Semiclassical non-trace-type formulas for matrix-element fluctuations and weighted densities of states.
Densities of states weighted with the diagonal matrix elements of two operators A and B, i.e., rho(A,B)(E)= summation operator(n)<nAn><nBn>delta(E-E(n)), cannot, in general, be written as a trace formula, and therefore no simple extension of semiclassical trace formulas is known for this case. However, from the high resolution analysis of quantum spectra in the semiclassical regime we find strong evidence that weighting the delta functions in the quantum mechanical density of states with the product of diagonal matrix elements, <nAn><nBn>, is equivalent to weighting the periodic orbit contributions in the semiclassical periodic orbit sum with the product of the periodic orbit means, <A>(p)<B>(p), of the classical observables A and B. Results are presented for the hydrogen atom in a magnetic field for both the chaotic and near-integrable regime, and for the circle billiard.


[Is reduction of hyperglycemia associated with a cardiovascular benefit?]
We have a large body of evidence showing that hyperglycemia is a cardiovascular risk factor and that its reduction decreases the risk for cardiovascular events. Indeed, epidemiological studies have clearly shown that hyperglycemia is a strong and independent factor for cardiovascular disease. In addition, we have many pathophysiological studies demonstrating the direct role of hyperglycemia in the development of atherosclerosis. Hyperglycemia, by stimulating protein kinase C, increases the production of pro-inflammatory cytokines, of adhesion molecules and of endothelin-1 and, by stimulating the polyol pathway, promotes the oxidative stress. Furthermore, chronic hyperglycemia leads to the accumulation of advanced glycation end-products that modify the structure of the arterial wall and, as a consequence, will increase the risk for the development of atherosclerosis. Moreover, prolonged intervention studies have shown that reduction of hyperglycemia is associated with a significant decrease in the risk for major cardiovascular events. Thus, hyperglycemia is a cardiovascular risk factor which is characterized by the fact that it induces profound modifications of the arterial wall and that it is necessary to correct hyperglycemia during enough time to obtain a cardiovascular benefit.


Predominant expression of exon 7 skipped SMN mRNAs in lung based on analysis of transcriptome sequencing datasets.
Spinal muscular atrophy (SMA) is caused by deletion of SMN1, one of the two SMN (Survival of Motor Neuron) genes. SMN2 is still present in SMA patients but its exon 7 is alternatively spliced. In this study, we took advantage of recent deposit of deep-sequencing datasets from a number of human tissues and examined the expression and splicing of SMN mRNA. We showed that SMN is slightly more abundantly expressed in the lungs and prostate. More interestingly, we found that the percentage of SMNΔ7 in lung and adipose tissue is significantly higher than in other tissues such as the testes, where almost no SMNΔ7 is expressed. Since SMN1 produces more than 95 % of full-length SMN RNA, it is likely that SMN2 has a higher skipping rate of exon 7 in adipose and lung tissue, leading to a higher ratio of SMNΔ7/SMN in these tissues. Given that many SMA patients die from respiratory failure, we speculate that higher skipping of exon 7 in the lungs may play a role in the progression of SMA.


Fabrication of electrochemical sensor for paracetamol based on multi-walled carbon nanotubes and chitosan-copper complex by self-assembly technique.
An electrochemical sensor for paracetamol based on multi-walled carbon nanotubes and chitosan-copper complex (MWCNTs/CTS-Cu) was fabricated by self-assembly technique. The MWCNTs/CTS-Cu modified GCE showed an excellent electrocatalytic activity for the oxidation of paracetamol, and accelerated electron transfer between the electrode and paracetamol. Under optimal experimental conditions, the differential pulse peak current was linear with the concentration of paracetamol in the range of 0.1-200 μmol L(-1) with a detection limit of 0.024 μmol L(-1). The sensitivity was found to be 0.603 A/mol L(-1). The proposed sensor also showed a high selectivity for paracetamol in the presence of ascorbic acid and dopamine. Moreover, the proposed electrode revealed good reproducibility and stability. The proposed method was successfully applied for the determination of paracetamol in tablet and human serum samples.


Cyclic inhibition-potentiation of the crosslinking of synapsin I with brain microtubules by protein kinase FA (an activator of ATP.Mg-dependent protein phosphatase).
The ATP.Mg-dependent type-1 protein phosphatase activating factor (FA) was identified as a protein kinase that could phosphorylate synapsin I, a neuronal protein that coats synaptic vesicles, binds to cytoskeleton and is believed to be involved in the modulation of neurotransmission. More importantly, more than 90% of the phosphates in 32P-synapsin I phosphorylated by FA could be removed by the activated ATP.Mg-dependent type-1 protein phosphatase and the synapsin I phosphatase activity was found to be strictly FA-dependent. Functional study further revealed that as a synapsin I kinase, factor FA could phosphorylate synapsin I and thereby inhibits crosslinking of synapsin I with tubulin, while as a synapsin I phosphatase activator, FA could promote the crosslinking copolymerization of synapsin I with tubulin. Taken together, the results provide initial evidence that a cyclic modulation of the crosslinking copolymerization of synapsin I with brain microtubules can be controlled by factor FA, representing an efficient cyclic cascade control mechanism for the regulation of axonal transport process during neurotransmission.


Evaluating the effectiveness of a clinical preceptorship program for registered nurses in jordan.
The authors implemented and evaluated a preceptor training program to prepare registered nurses to become preceptors and to establish a nursing preceptor training program to promote knowledge of preceptorship among Jordanian nurses. A true experimental design was used. The sample consisted of 68 registered nurses recruited randomly from governmental, private, and university hospitals. A sociodemographic data form and a questionnaire on nurses' knowledge about preceptorship were developed for self-administration. The study results showed that the difference between the experimental (n = 30, M = 33/41, SD = 4.5) and control (n = 38, M = 26/41, SD = 4.6) groups after implementation of the preceptorship program was statistically significant (t = 5.5, df = 66, p = .000). The preceptorship program showed significant improvement in participants' knowledge of clinical teaching.


Regioselective di- and tetra-functionalisation of γ-cyclodextrin using capping methodology.
Alkylation of γ-cyclodextrin with 3 equiv. of 1,3-bis[bis(4-tert-butylphenyl)chloromethyl]benzene, followed by permethylation afforded selectively a singly capped (A,B), as well as two doubly capped (A,B:D,E and A,B:E,F) methylated γ-CDs. Deprotection with HBF4 gave quantitatively the corresponding diols and tetrols, which constitute valuable starting compounds for further functionalisation.


Fast capillary electrophoresis method for determination of docosahexaenoic and eicosapentaenoic acids in marine oils omega-3 supplements.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential omega-3 fatty acids (FA) in human nutrition. Dietary supplements containing these FA are available in the market and there is a need to assess their quality to prevent frauds. The purpose of this work was to optimize and validate a fast capillary electrophoresis (CE) method to determine EPA and DHA content in marine oils omega-3 supplements. Sample preparation comprised only a saponification step and analysis time was 8 min. Validation was performed according to limits of detection and quantification, linearity, accuracy and repeatability. Ten real samples of marine oil supplements were analyzed by CE and compared to conventional gas chromatography method. No significant differences between both methods were found within 95% confidence interval. Overall, CE method was successful to FA quantification and it could be used for fast FA monitoring during omega-3 supplement manufacture, final product quality assurance and labelling.


Identification of in vivo phosphorylation sites of SET, a nuclear phosphoprotein encoded by the translocation breakpoint in acute undifferentiated leukemia.
SET, the translocation breakpoint-encoded protein in acute undifferentiated leukemia (AUL), is identified as a 39-kDa phosphoprotein found predominantly in the cell nuclei [1994, J. Biol. Chem. 269, 2258-2262]. SET is fused to a putative oncoprotein, CAN, in AUL and is thought to regulate the transformation potential of SET-CAN by its nuclear localization and phosphorylation. We investigated in detail the in vivo phosphorylation of SET. Phosphorylation of SET occurred in all human cell lines examined in vivo, primarily on serine residues. Endoproteinase Glu-C digestion of phosphorylated SET yielded two phosphopeptides. By radiosequencing, we identified the in vivo phosphorylation sites of SET as Ser9 and Ser24. The surrounding sequences of Ser9 and Ser24 contained an apparent consensus site sequence for protein kinase C.


Relationship of circadian temperature and activity rhythms in two rodent species.
Despite the large number of publications concerning circadian body temperature in rodents, relatively little is known about phase relationships of the body temperature cycle relative to daily locomotor rhythms. Phase angle differences between core body temperature and locomotor activity were determined by a group of overlapping methods for 14 hamsters and 11 chipmunks under constant light (LL) and entrained (LD) photo schedules. The study compared the onset of the body temperature cycle with three separate components of daily locomotor activity: the onset of wheel running, the onset of total activity in a standard wheel cage, and the onset of total activity in a restricted cage, respectively. The temperature cycle showed a pronounced phase lead over onset of wheel-running activity in all hamsters and in the majority of chipmunks, but the phase lead was reduced when total activity was considered. With activity restriction, the onset of temperature rise and activity onset concurred. The body temperature onset in some species may serve as a valid phase point for indirect measurement of circadian timing, but the potential artifact of masking by heat generated from muscular activity should be kept clearly in mind.


Experimental observation of energy modulation in electron beams passing through terahertz dielectric wakefield structures.
We report the observation of a strong wakefield induced energy modulation in an energy-chirped electron bunch passing through a dielectric-lined waveguide. This modulation can be effectively converted into a spatial modulation forming microbunches with a periodicity of 0.5-1 ps and, hence, capable of driving coherent terahertz radiation. The experimental results agree well with theoretical predictions.


Imaging evaluation of blood supply changes after chemotherapy of osteosarcoma and its correlation with tumor necrosis rate.
Analysis of the tumour necrosis rate is an important method to evaluate the effect of neoadjuvant chemotherapy for osteosarcoma. However, at present, there is no specific imaging method to evaluate this effect. The purpose of this study was to evaluate the changes in blood supply after chemotherapy by measuring the CT enhancement rate and to analyse the correlation between the CT enhancement rate and the tumour necrosis rate. Patients with primary osteosarcoma of the extremities treated in our institute from 2016 to 2017 were analysed retrospectively. In total, 103 eligible patients were enrolled in the study, including 67 males and 36 females, with an average age of 17.7 (6-54) years. Sixty cases had tumour sites in the femur, 25 in the tibia, 10 in the humerus, and eight in other sites. All patients received neoadjuvant chemotherapy including methotrexate, cisplatin + doxorubicin and ifosfamide before surgical treatment. All patients underwent enhanced CT examination of the same tumour site before and after the neoadjuvant chemotherapy protocol. The CT value before and after chemotherapy was measured and the enhancement rate was calculated. The change in the CT enhancement rate after chemotherapy was analysed. Changes in the CT enhancement rate were compared between patients with a tumour necrosis rate greater than 90% and those with one <90%. The average CT enhancement rates before and after chemotherapy were 1.68 (median 1.63, range 1.00-2.51) and 1.39 (median 1.28, range 1.00-2.83), respectively (P < 0.01). The average CT enhancement rate after chemotherapy decreased by 15.0% (median 16.7%, range -27.5-53%): 75 cases exhibited a decrease, three cases remained unchanged, and 25 cases exhibited an increase. The average enhancement rate before chemotherapy was 1.75 (median 1.68, range 1.18-2.51) in the group with a necrosis rate >90% and 1.62 (median 1.52, range 1.00-2.41) in the group with a necrosis rate < 90% (P = 0.068). The average CT enhancement rate after chemotherapy was 1.20 (median 1.21, range 1.00-1.53) in the group with a necrosis rate > 90% and 1.53 (median 1.43, range 1.00-2.83) in the group with a necrosis rate < 90% (P < 0.01). The enhancement rate of the group with a necrosis rate > 90% decreased by 29.0% (median 28%, range -2.3-53%) (P < 0.01); the enhancement rate of the group with a necrosis rate < 90% decreased by 3.8% on average (median 0.7%, range -27.5-44.5%) (P = 0.225). After receiving neoadjuvant chemotherapy, most patients with osteosarcoma of the extremities exhibited reductions in the CT enhancement rate. In cases where the tumour necrosis rate was greater than 90%, the tumour blood supply was significantly reduced. This suggests that imaging evaluations based on the CT enhancement rate can be used as a reference for evaluating the preoperative effect of chemotherapy for osteosarcoma.


Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics.
Viridans group streptococci (VGS), especially the Streptococcus mitis-oralis subgroup, are pivotal pathogens in a variety of invasive endovascular infections, including "toxic shock" in neutropenic cancer patients and infective endocarditis (IE). Previously, we showed that the serial in vitro passage of S. mitis-oralis strains in sublethal daptomycin (DAP) resulted in rapid, high-level and stable DAP-resistance (DAP-R), which is accompanied by distinct changes in several genotypic and phenotypic signatures: (1) the disappearance of two key membrane phospholipids, phosphatidylglycerol (PG) and cardiolipin (CL); (2) increased membrane fluidity; (3) increased positive surface charge; (4) single nucleotide polymorphisms (SNPs) in two loci involved in CL biosynthesis (pgsA; cdsA); and (5) DAP hyperaccumulation. The current study examined these same metrics following in vitro serial DAP passages of a separate well-characterized S. mitis-oralis bloodstream isolate (SF100). Although some metrics seen in prior DAP post-passage strains were recapitulated with SF100 (e.g., pgsA SNPs, enhanced membrane fluidity), we observed the following major differences (comparing the parental versus post-passage variant): (1) no change in PG content; (2) reduced, but not absent, CL, with enhancement in phosphatidic acid (PA) content; (3) an unusual pattern of CL localization; (4) significantly decreased positive surface charge; (5) no difference in DAP accumulation; and (6) no cdsA SNPs. Thus, S. mitis-oralis strains are not "pre-programmed" phenotypically and/or genotypically to adapt in an identical manner during the evolution of the DAP-R.


Polymerase chain reaction compared with concurrent viral cultures for rapid identification of human immunodeficiency virus infection among high-risk infants and children.
To determine the usefulness of DNA amplification by polymerase chain reaction for the early identification of human immunodeficiency virus type 1 (HIV-1) infection in infants and children, we compared the polymerase chain reaction and concurrent viral cultures of peripheral blood mononuclear cells from 25 high-risk subjects aged 5 weeks to 8 years. In two separate primer pairs, HIV-1 proviral DNA gag sequences were successfully identified in cell lysates from seven patients, including two infants with previously indeterminate HIV-1 status on the basis of serologic and culture results. In the remaining 18 patients the polymerase chain reaction was negative for HIV-1. Simultaneously grown HIV-1 cultures concurred with polymerase chain reaction results for all patients. In an 18-month-old infant who had had a single HIV-1 positive culture at 1 month of age with four subsequent negative cultures, both polymerase chain reaction and HIV-1 culture were negative. Our data demonstrate the clinical applicability of polymerase chain reaction on crude cell lysates for the rapid, early, definitive detection of HIV-1 infection in high-risk infants and children.


Enterocin TW21, a novel bacteriocin from dochi-isolated Enterococcus faecium D081821.
Purification and characterization of a novel bacteriocin produced by strain Enterococcus faecium D081821. Enterococcus faecium D081821, isolated from the traditional Taiwanese fermented food dochi (fermented black beans), was previously found to produce a bacteriocin against Listeria monocytogenes and some Gram-positive bacteria. This bacteriocin, termed enterocin TW21, was purified from culture supernatant by ammonium sulfate precipitation, Sep-Pak C18 cartridge, ion-exchange and gel filtration chromatography. Mass spectrometry analysis showed the mass of the peptide to be approximately 5300·6 Da. The N-terminal amino acid sequencing yielded a partial sequence NH2 -ATYYGNGVYxNTQK by Edman degradation, and it contains the consensus class IIa bacteriocin motif YGNGV in the N-terminal region. The open reading frame (ORF) encoding the bacteriocin was identified from the draft genome sequence of Enterococcus faecium D081821, and sequence analysis of this peptide indicated that enterocin TW21 is a novel bacteriocin. Enterococcus faecium D081821 produced a bacteriocin named enterocin TW21, the molecular weight and amino acid sequence both revealed it to be a novel bacteriocin. A new member of class IIa bacteriocin was identified. This bacteriocin shows great inhibitory ability against L. monocytogenes and could be applied as a natural food preservative.


alpha-Mannosidase activity from antibody raised against a glucal antigen.
Sixty cell lines of monoclonal antibody were raised against a glucal hapten 1. Among them, Ab 405.4 showed alpha-mannosidase activity as kcat = 0.19/day (kcat/kuncat = 110,000). The chemical modification study and pH profile study of this antibody indicated that carboxyl group(s) in the antigen binding site involved in catalytic mechanism.


Duration and structure of unaccompanied (dyadic) and accompanied (triadic) initial outpatient consultations in a specialist seizure clinic.
This study explores differences in the duration and structure of unaccompanied (dyadic) and accompanied (triadic) initial (diagnostic) outpatient consultations in a specialist seizure clinic. This is the first known study to explore this topic quantitatively by analyzing the discourse space taken up by the different participants in real clinical encounters. We did not observe significant differences between the duration of accompanied and unaccompanied interactions (p=0.589). Results suggest that patients occupy proportionally less discourse space (measured by the number of words produced) in accompanied interactions than in unaccompanied interactions (56.9% versus 28.3%, p ≤ 0.0001). In accompanied interactions, there is a weak negative correlation between the discourse space of patients and that of doctors (rs=-0.43, p=0.017) and a moderate to strong negative correlation with the discourse spaces of companions (rs=-0.64, p=0.001). These findings indicate that the presence of a companion may reduce opportunities for doctors to observe the interactional, linguistic, and topical features of seizure patient talk, whose differential diagnostic value has been described in a number of previous publications, or for patients to raise issues they want to talk about.


Dehydration modifies guanidino compound concentrations in the different zones of the rat kidney.
Guanidino compounds (GCs) related to arginine (Arg) are unevenly distributed along the cortico-papillary axis of the rat kidney. Inasmuch as the concentration of alpha-keto-delta-guanidinovaleric acid (alpha-keto-delta-GVA), guanidinosuccinic acid (GSA), creatinine (CTN), gamma-guanidinobutyric acid (gamma-GBA) and methylguanidine (MG) increased steeply along the inner medulla in parallel to the urea and osmotic gradients, the question arose as to whether dehydration enhances their renal content and distribution. To examine this possibility, adult male rats were dehydrated by removing the drinking water for 24 or 48 h. The kidneys were sliced and cut in seven sections along the cortico-papillary axis. Twelve GCs were determined by liquid chromatography in each renal zone. Dehydration modified GC concentrations and regional distribution. The renal content of Arg, guanidine and MG was decreased while that of alpha-keto-delta-GVA, gamma-GBA, alpha- N-acetyl-arginine and homoarginine remained unchanged. In contrast, GSA, guanidinoacetic acid (GAA), creatine (CT), CTN and beta-guanidinopropionic acid (beta-GPA) concentrations were enhanced significantly in different renal zones after 24 and 48 h dehydration. In addition, the tissue level of GCs supplying energy, such as CT and beta-GPA, the precursor of CT (GAA) and its metabolite (CTN) were enhanced under dehydration. Arg and CT account for 80-90% of the GCs located in the renal cortex. Variations of some GC levels under dehydration may modify enzyme activities, renal metabolism and cell function.


The testis-specific VAD1.3/AEP1 interacts with β-actin and syntaxin 1 and directs peri-nuclear/Golgi expression with bipartite nucleus localization (BNL) sequence.
VAD1.3 (AEP1), a novel testis-specific gene, was first isolated from the testis of a retinol-treated vitamin-A-deficient (VAD) rat model. It is expressed at the acrosomal region of spermatids from postnatal day 25. VAD1.3 immunoreactivity is present in rat, human, monkey and porcine spermatids and spermatozoa, suggesting that VAD1.3 may play a role in acrosome formation. However, direct evidence on the detailed sub-cellular localization of the VAD1.3 protein in the acrosome and how VAD1.3 is involved in acrosome formation remains largely unknown. Here, we isolated and identified VAD1.3 interacting proteins by immunoprecipitation followed by mass spectrometry, and determined the functional motifs of VAD1.3 that were important for its specific sub-cellular location in vitro. We found that VAD1.3 bound to syntaxin 1 and β-actin proteins in vitro. Immunogold electron microscopic study localized VAD1.3 immunoreactivity to the acrosome membranes and matrix, and colocalized it with the β-actin protein. The full-length GFP-VAD (1-3601) and GFP-VAD (1-730) fusion proteins that contain the bipartite nucleus localization (BNL) signal were located in the peri-nucleus/Golgi of the transfected cells. In addition, the GFP signal colocalized with the endoplasmic reticulum marker and the syntaxin 1 protein in the transfected HeLa and GC-2spd cells. The C-terminal GFP-VAD (1770-3601) was expressed in the nucleus. Taken together, VAD1.3 interacts with β-actin and syntaxin 1 in vitro. The BNL signal may mediate the peri-nuclei localization of the protein that may interact with syntaxin 1 and β-actin for acrosome formation in spermatogenesis.


[A new method for treating chronic blepharitis using magnetic compounds and an alternating magnetic field].
Discusses a new method of clinical use of alternating magnetic field from 0.1 to 0.25 T and of a magnetic ointment composition with reduced iron powder in patients with chronic blepharitis. Such treatment was found fairly effective, reducing the rehabilitation periods 2-3-fold and giving a good clinical effect (41-87%).


Juvenile hormone regulation of mRNA levels for a highly abundant hemolymph protein in larval Trichoplusia ni.
Several hemolymph proteins ranging in size from 73 to 76 kDa increase to very high levels just prior to metamorphosis in Trichoplusia ni (Lepidoptera). One of these proteins (pI = 5.8, Mr = 76,000) was selected for a study of hormonal regulation. The appearance of this protein could be suppressed in vivo by topical treatment with the juvenile hormone analog fenoxycarb. An antiserum for this protein was prepared and shown to react selectively with the 76-kDa protein in whole hemolymph. Translation of poly(A)-containing RNA from untreated larvae yielded the 76-kDa protein, whose identity was verified with the antibody, whereas mRNA from juvenile hormone analog-treated larvae did not. These data indicate that juvenile hormone acts to regulate the level of the mRNA of this hemolymph protein.


The treatment of venous thrombosis of the upper and lower limbs with "APSAC" (p-anisoylated streptokinase-plasminogen complex).
APSAC, administered by bolus injection, has been used to treat 28 patients: 14 with ilio-femoral venous thrombosis, 6 with "spontaneous" axillary-subclavian thrombosis and eight with superior vena-caval thrombosis associated with parenteral nutrition catheter. Four of the patients with lower limb deep vein thrombosis (DVT) showed partial lysis whereas the remaining 10 showed no change. Of the patients with upper limb and/or superior caval DVT seven showed complete lysis three showed partial lysis and four showed no benefit. APSAC is an effective treatment of venous thrombosis of the upper limbs.


Role of maternal viremia and placental infection in hepatitis B virus intrauterine transmission.
The mechanism of intrauterine hepatitis B virus infection has not been established. In this study, venous blood, cord blood, and placental tissues from 171 chronic hepatitis B virus infected pregnant women were tested for hepatitis B surface antigen, hepatitis B core antigen, and hepatitis B virus DNA. We found that residence, mode of delivery, age, and number of gestational weeks of pregnant women were not correlated with intrauterine hepatitis B virus infection, while neonates of mothers who were hepatitis B s antigen positive and hepatitis B e antigen positive (P < 0.01) or who had high hepatitis B virus DNA levels (≥10(6) copies/ml) were more likely to get an intrauterine infection (P < 0.01). The hepatitis B virus infection rate in placental cell layers gradiently decreased from the mother's side to the fetus's side of the placenta, but the odds ratio value of correlation between placental hepatitis B virus infection and intrauterine infection gradiently increased. The way of intrauterine hepatitis B virus infection may be through a layer-layer transmission pathway, although the possibility of placental leakage cannot be excluded.


Users' needs and expectations of electronic medical record systems in family medicine residence settings.
While physician informational needs have been examined in the literature, rarely do the findings have the specificity required to drive development of Electronic Medical Records (EMRs) features. Using Delphi methodology, a comprehensive list of desirable, ranked EMR features was developed for physician residency practices. The identified EMR features and implications for system development are explored in this paper.


Mathematical model for hybrid and panoramic stereovision systems: panoramic to rectilinear conversion model.
This paper introduces a new generic model for a stereovision system composed of a perspective camera and a panoramic camera or of two panoramic cameras. We present a new simple model in order to establish matching images and to formulate 3D reconstruction. Indeed, we show that composed cubic splines functions are suitable for conventional and wide-angle cameras and accurately model tangential and radial distortions. Matching is greatly simplified using this technique, and classical methods can be used to evaluate the relationship between image pairs and to achieve 3D reconstruction. Such a technique allows us to model complex forms of distortions, as in the case for panomorph lenses.


Motor somatotopy in the striatum of rat: manipulation, biting and gait.
The objective of this study was to examine the hypothesis of somatotopically organized motor functions in the striatum. In Experiment 1, ibotenate-induced lesions of the rostrolateral striatum in rats produced a transient decrease of ad libitum food intake, a more enduring decrease of body weight, and chronic impairments of food biting, holding of hard food pellets and feeding efficiency, with no apparent alterations of gait balance in a beam walking task. Lesions of the medial striatum had minimal or no reliable effects on any of the measured parameters. In Experiment 2, the motoric effects of ibotenate lesions restricted to either the dorsomedial or the dorsolateral or the ventrolateral regions of the rostral striatum were examined. Lesions of the dorsolateral striatum produced the most deleterious effect on holding postures of the forelimbs, whereas lesions of the ventrolateral striatum maximally affected food biting, feeding efficiency, ad libitum food intake, and body weight. No regional lesions affected gait balance. Dorsomedial striatal lesions did not affect any of the measured parameters. The findings support the hypothesis of a somatotopically organized role of the rostrolateral striatum in orofacial and forelimb motor control.


Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis.
Histopathologic examination and clinical observations of solid and haematological malignancies indicates mast cells as key host cells in the tumour infiltrate, with important consequence on tumour-associated angiogenesis and tumour growth. Data suggest indeed that tumour-infiltrating mast cells may exert a prominent function in the angiogenic "switch", which is essential for the progression of early tumours. The experimental approach has substantially increased our understanding of the role of tumour-infiltrating mast cells in the process of angiogenesis that accompanies tumour development. This review will focus on the crucial contribution of mast cells in promoting tumour neovascularization as it emerges from the most recent observations of experimental carcinogenesis in in vivo and in vitro models.


[Ganciclovir treatment failure in adult allogeneic hematopoietic stem cell transplant recipients with cytomegalovirus infection--a single centre experience].
To determine the incidence of infection with ganciclovir-resistant cytomegalovirus (CMV) in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. Clinical resistance or treatment failure was defined as persistent DNAemia or increasing viral load in peripheral blood after 2 weeks of virostatic treatment. The association between the treatment failure and viral resistance was analysed. The presence of ganciclovir-resistant CMV strains was confirmed by genotypic testing able to detect mutations conferring resistance. In 2012 and 2014, 40 patients who underwent allogeneic HSCT for hematologic malignancies and were treated for human CMV reactivation/disease were followed up prospectively. In patients with treatment failure, CMV DNA was isolated and analysed by nucleotide sequence analysis of the UL 97 and UL 54 genes conferring resistance to the virostatic agent. The treatment failure occurred in seven patients, but ganciclovir resistance conferring mutations were only detected in two of them (mutations L595F and M460I in the UL 97 gene). Another mutation in the UL 97 gene (N510S) was found in a patient with recurrent CMV replication who needed to be retreated but did not meet the criteria for treatment failure. The low incidence of genetically confirmed ganciclovir-resistant CMV isolates in HSCT recipients with relatively common clinical treatment failure suggests that the mechanism underlying slower viral clearance is often other than mutations conferring ganciclovir resistance to the virus.


Fiber Bragg grating temperature sensor with controllable sensitivity.
We demonstrate a fiber Bragg grating (FBG) sensor with controllable sensitivity by connecting two metal strips that have different temperature-expansion coefficients. By changing the lengths of the metal strips we successfully controlled and improved the temperature sensitivity to 3.3 times of that of bare FBG.


Idiopathic hemochromatosis and iron overload in alcoholic liver disease: differentiation by HLA phenotype.
HLA A and B antigens were determined in two groups of patients: 38 patients with idiopathic hemochromatosis (IH) and 22 patients with iron overload accompanying alcoholic liver disease (AH). As previously described, HLA A3 and HLA B14 antigens appeared more frequently in the IH group (76.3 and 28.9%, respectively) than in a control group of 204 subjects (27 and 3.4%). In the AH group the frequency of A3 (22.7%) and B14 (13.6%) was not significantly different from that observed in controls. The frequency of A3 was significantly lower in the AH group than in the IH group (P less than 0.001). On this basis a clear difference appears between the two conditions with iron overload, and genetic analysis of the results rules out the hypothesis that AH would be a heterozygous form of IH exposed by alcohol.


[Combined use of iodine 123 and technetium 99m pertechnetate in a recurring struma ovarii].
A case of ovaric strauma diagnosed with combine use of I123 and tecnesium 99m pertecnetate is presented. We believe that I123 is more useful than I131 for the detection of ectopic thyroid tissue.