The Comparison of Local Infiltration Analgesia with Peripheral Nerve Block following Total Knee Arthroplasty (TKA): A Systematic Review with Meta-Analysis.
Total knee arthroplasty (TKA) is usually associated with severe post-operative pain, which can prevent rehabilitation of patients' knee function and influence the satisfaction of surgery. Local infiltration analgesia (LIA) is a method that has been applied in clinical practice recently. However, the clinical use of this method is still under discussion. In this paper, we systematically reviewed randomized clinical trails (RCTs) comparing LIA with peripheral nerve block (PNB) to verify the efficacy and safety of LIA. During the analysis, we strictly filtered papers and chose ones that had fewer disturbance variables. We also analyzed the heterogeneity. We conclude that when compared with PNB, pain control with LIA is at least comparable.


The effect of intraperitoneal progesterone on postoperative adhesion formation in rabbits.
The immunosuppressive and anti-inflammatory properties of progesterone (P) have been established. The authors investigated whether the intraperitoneal instillation of P would lessen postoperative adhesion formation in New Zealand white rabbits undergoing pelvic surgical procedures. In phase I, severe, peritoneal lesions were made in the right uterine horn (n = 48). Animals were randomized to receive equal volumes of either (1) Ringer's lactate (RL); (2) 32% dextran 70 (HY; Hyskon Division, Pharmacia, Piscataway, NJ); (3) 500 mg P in oil (PO); or (4) 500 mg aqueous P (PA) at initial laparotomy. In phase II, the distal right uterine horn, including the mesosalpinx, was excised and microsurgical anastomosis was accomplished (n = 45). Aqueous P was not used in phase II; otherwise, the same agents were tested. Six weeks later, the severity of the adhesions formed was graded. The mean adhesion scores for the RL and HY groups were low for the right side in both phases and did not differ (P greater than 0.05). In contrast, higher scores were observed in all the P groups, regardless of the P preparation used or the surgical procedure performed (P less than 0.05).


Dendritic extent in human CA2-3 hippocampal pyramidal neurons in normal aging and senile dementia.
The extent of dendritic trees of pyramidal neurons of the CA2-3 field of the hippocampus of 20 human brains obtained at autopsy was quantified in Golgi Cox-stained tissue. Fifteen cases were neurologically and psychiatrically normal and ranged in age from 43 to 95 years. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of both the apical and basal trees of CA2-3 pyramidal neurons was found to be unchanged from middle age to very old age. This finding of net stability of dendritic extent is in contrast to previous quantitative reports of either continued dendritic growth in human parahippocampal gyrus or of dendritic growth followed by regression in human dentate gyrus. This finding is consistent with the suggestion that changes in dendritic extent in normal aging are a function of the balance between regressive and proliferative influences and are region specific. In cases with SD, dendritic extent of both the apical and basal trees was found to be similar to that of the normal age-matched cases. These data are consistent with those of others suggesting relative sparing of the CA2-3 field from the degenerative changes in senile dementia.


DNA polymerase insertion fidelity. Gel assay for site-specific kinetics.
A quantitative assay based on gel electrophoresis is described to measure nucleotide insertion kinetics at an arbitrary DNA template site. The assay is used to investigate kinetic mechanisms governing the fidelity of DNA synthesis using highly purified Drosophila DNA polymerase alpha holoenzyme complex and M13 primer-template DNA. Km and Vmax values are reported for correct insertion of A and misinsertion of G, C, and T opposite a single template T site. The misinsertion frequencies are 2 X 10(-4) for G-T and 5 X 10(-5) for both C-T and T-T relative to normal A-T base pairs. The dissociation constant of the polymerase-DNA-dNTP complex, as measured by Km, plays a dominant role in determining the rates of forming right and wrong base pairs. Compared with Km for insertion of A opposite T (3.7 +/- 0.7 microM), the Km value is 1100-fold greater for misinsertion of G opposite T (4.2 +/- 0.4 mM), and 2600-fold greater for misinsertion of either C or T opposite T (9.8 +/- 4.2 mM). These Km differences indicate that in the enzyme binding site the stability of A-T base pairs is 4.3 kcal/mol greater than G-T pairs and 4.9 kcal/mol greater than C-T or T-T pairs. In contrast to the large differences in Km, differences in Vmax are relatively small. There is only a 4-fold reduction in Vmax for insertion of G opposite T and an 8-fold reduction for C or T opposite T, compared with the correct insertion of A. For the specific template T site investigated, the nucleotide insertion fidelity for Drosophila polymerase alpha seems to be governed primarily by a Km discrimination mechanism.


Membrane resistance and shunting inhibition: where biophysics meets state-dependent human neurophysiology.
Activation of neurons not only changes their membrane potential and firing rate but as a secondary action reduces membrane resistance. This loss of resistance, or increase of conductance, may be of central importance in non-invasive magnetic or electric stimulation of the human brain since electrical fields cause larger changes in transmembrane voltage in resting neurons with low membrane conductances than in active neurons with high conductance. This may explain why both the immediate effects and after-effects of brain stimulation are smaller or even reversed during voluntary activity compared with rest. Membrane conductance is also increased during shunting inhibition, which accompanies the classic GABAA IPSP. This short-circuits nearby EPSPs and is suggested here to contribute to the magnitude and time course of short-interval intracortical inhibition and intracortical facilitation.


"Wave" as defined by wave intensity analysis.
The propagation of waves in the arteries is generally described using Fourier analysis in terms of periodic wavetrains formed by the superposition of a mean value and sinusoidal waves at the fundamental frequency (defined by the heart rate) and its harmonics. There is, however, an alternative way to describe waves in the vasculature based upon the method-of-characteristics solution of 1-D conservation laws. This method, wave intensity analysis (WIA), can be used to describe periodic waves but can also be used to describe the propagation of non-periodic waves that cannot be practically described in terms of sinusoidal wavetrains. As a means of demonstrating how WIA defines a wave, we used data gathered in a simple bench-top experiment where a single disturbance propagated along a single elastic tube and was reflected and re-reflected between a closed and a relatively open end. Results demonstrate that forward- and backward-travelling peaks of intensity usefully define wave interactions.


Tctex1 plays a key role in the α-synuclein autophagy lysosomal degradation pathway.
Tctex1 is an important structure of dynein light chain in mammalian cells, clarifying the role of Tctex1 in α-synuclein autophagy lysosomal degradation may offer insights into the formation of Lewy bodies and neuronal death. We constructed dsRED-N1-Tctex1 overexpression, pDsRED2-N1-Tctex1(T94E) mutation and transfected into SH-SY5Y cells. Relative protein expression was measured by Western Blot and mRNA levels were measured by real-time quantitative PCR. Confocal microscopy was used to observe their sublocalizations in cells. We found that: WST assay results show that cell activity decreased after Tctex1 mutation (T94E), while Tctex1 overexpression increased cell activity. In Tctex1 mutation transfected cell lines Tctex1 and dynein protein levels decreased; α-synuclein, LC3-II and LAMP2 protein increased. However, α-synuclein, LC3-II and LAMP2 proteins were reduced in Tctex1 overexpression cell lines, with the same trend was found in mRNA levels. In Tctex1 mutation transfected cell lines Tctex1 fluorescence intensity weakened; α-synuclein, LC3-II and LAMP2 fluorescence was enhanced, while α-synuclein, LC3-II and LAMP2 weakened in Tctex1 overexpressing cells. Our results suggest that Tctex1 mutants interference lead to Tctex1 downregulation and dysfunction. Tctex1 overexpression promoted autophagy lysosome fusion and effectively degraded α-synuclein with increased cell activity. Thus, Tctex1 plays an important role in α-synuclein autophagic degradation.


Radical prostatectomy versus external beam radiotherapy with androgen deprivation therapy for high-risk prostate cancer: a systematic review.
To summarize recent evidence in terms of health-related quality of life (HRQoL), functional and oncological outcomes following radical prostatectomy (RP) compared to external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high-risk prostate cancer (PCa). We searched Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Controlled Trial Register and the International Standard Randomized Controlled Trial Number registry on 29 march 2021. Comparative studies, published since 2016, that reported on treatment with RP versus dose-escalated EBRT and ADT for high-risk non-metastatic PCa were included. The Newcastle-Ottawa Scale was used to appraise quality and risk of bias. A qualitative synthesis was performed. Nineteen studies, all non-randomized, met the inclusion criteria. Risk of bias assessment indicated low (n = 14) to moderate/high (n = 5) risk of bias. Only three studies reported functional outcomes and/or HRQoL using different measurement instruments and methods. A clinically meaningful difference in HRQoL was not observed. All studies reported oncological outcomes and survival was generally good (5-year survival rates > 90%). In the majority of studies, a statistically significant difference between both treatment groups was not observed, or only differences in biochemical recurrence-free survival were reported. Evidence clearly demonstrating superiority in terms of oncological outcomes of either RP or EBRT combined with ADT is lacking. Studies reporting functional outcomes and HRQoL are very scarce and the magnitude of the effect of RP versus dose-escalated EBRT with ADT on HRQoL and functional outcomes remains largely unknown.


Intramedullary ependymoma producing collagen. A clinical and pathological study.
The authors describe the clinical and pathological observations of a thoracolumbar intramedullary ependymoma. A voluminous conus of collagenous tissue was located in the center of the tumor. This most unusual histological finding is compared to rare cases of the literature describing the presence of bone and cartilage in ependymomas.


MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis.
Bone metastasis is one of the most serious complications in lung cancer patients. MicroRNAs (miRNAs) play important roles in tumour development, progression and metastasis. A previous study showed that miR-106a is highly expressed in the tissues of lung adenocarcinoma with bone metastasis, but its mechanism remains unclear. In this study, we showed that miR-106a expression is dramatically increased in lung cancer patients with bone metastasis (BM) by immunohistochemical analysis. MiR-106a promoted A549 and SPC-A1 cell proliferation, migration and invasion in vitro. The results of bioluminescence imaging (BLI), micro-CT and X-ray demonstrated that miR-106a promoted bone metastasis of lung adenocarcinoma in vivo. Mechanistic investigations revealed that miR-106a upregulation promoted metastasis by targeting tumour protein 53-induced nuclear protein 1 (TP53INP1)-mediated metastatic progression, including cell migration, autophagy-dependent death and epithelial-mesenchymal transition (EMT). Notably, autophagy partially attenuated the effects of miR-106a on promoting bone metastasis in lung adenocarcinoma. These findings demonstrated that restoring the expression of TP53INP1 by silencing miR-106a may be a novel therapeutic strategy for bone metastatic in lung adenocarcinoma.


Dual targeting of TGF-β and PD-L1 inhibits tumor growth in TGF-β/PD-L1-driven colorectal carcinoma.
Immunosuppressive factors within the tumor microenvironment (TME), such as Transforming growth factor beta (TGF-β), constitute a crucial hindrance to immunotherapeutic approaches in colorectal cancer (CRC). Furthermore, immune checkpoint factors (e.g., programmed death-ligand 1 [PD-L1]) inhibit T-cell proliferation and activation. To cope with the inhibitory effect of immune checkpoints, the therapeutic value of dual targeting PD-L1 and TGF-β pathways via M7824 plus 5-FU in CRC has been evaluated. Integrative-systems biology approaches and RNAseq were used to assess the differential level of genes associated with 88 metastatic-CRC patients. The level of PD-L1 and TGF-β was evaluated in a validation cohort. The anti-proliferative, migratory, and apoptotic effects of PD-L1/TGF-β inhibitor, M7824, were assessed by MTT, wound-healing assay, and flow cytometry. Anti-tumor activity was assessed in a xenograft model, followed by biochemical studies and histological staining, and gene/protein expression analyses by RT-PCR and ELISA/IHC. The result of differentially expressed genes (DEGs) analysis showed 1268 upregulated and 1074 downregulated genes in CRC patients. Among the highest scoring genes and dysregulated pathways associated with CRC, PD-L1, and TGF-β were identified and further validated in 92 CRC patients. Targeting of PD-L1-TGF-β inhibited cell growth and migration, associated with modulation of CyclinD1 and MMP9. Furthermore, M7824 inhibited tumor growth via targeting TGF-β and PD-L1 pathways, resulting in modulation of inflammatory response and fibrosis via TNF-α/IL6/CD4-8 and COL1A1/1A2, respectively. In conclusion, our data illustrated that co-targeting PD-L1 and TGF-β pathways increased the effect of Fluorouracil (5-FU) and reduced the tumor growth in PD-L1/TGF-β expressing tumors, providing a new therapeutic option in the treatment of CRC.


Salt Adaptation and Evolutionary Implication of a Nah-related PAHs Dioxygenase cloned from a Halophilic Phenanthrene Degrading Consortium.
Polycyclic aromatic hydrocarbons (PAHs) pollutions often occur in marine and other saline environment, largely due to anthropogenic activities. However, study of the PAHs-degradation genotypes in halophiles is limited, compared with the mesophilic terrestrial PAHs degraders. In this study, a bacterial consortium (CY-1) was enriched from saline soil contaminated with crude oil using phenanthrene as the sole carbon source at 10% salinity. CY-1 was dominated by the moderate halophilic Marinobacter species, and its dominant PAHs ring-hydroxylating dioxygenase (RHD) genotypes shared high identity to the classic nah-related RHDs found in the mesophilic species. Further cloning of a 5.6-kb gene cluster from CY-1 unveiled the existence of a new type of PAHs degradation gene cluster (hpah), which most probably evolves from the nah-related gene clusters. Expression of the RHD in this gene cluster in E. coli lead to the discovery of its prominent salt-tolerant properties compared with two RHDs from mesophiles. As a common structural feature shared by all halophilic and halotolerant enzymes, higher abundance of acidic amino acids was also found on the surface of this RHD than its closest nah-related alleles. These results suggest evolution towards saline adaptation occurred after horizontal transfer of this hpah gene cluster into the halophiles.


The chemokine networks in sponges: potential roles in morphogenesis, immunity and stem cell formation.
Porifera (sponges) are now well accepted as the phylum which branched off first from the common ancestor of all metazoans, the Urmetazoa. The transition to the Metazoa became possible because during this phase, cell-cell as well as cell-matrix adhesion molecules evolved which allowed the formation of a colonial stage of animals. The next prerequisite for the evolution to the Urmetazoa was the establishment of an effective immune system which, flanked by apoptosis, allowed the formation of a first level of individuation. In sponges (with the model Suberites domuncula and Geodia cydonium), the main mediators of the immune responses are the chemokines. Since sponges lack a vascular system and consequently blood cells (in the narrow sense), we have used the term chemokines (in a broad sense) to highlight that the complex network of intercellular mediators initiates besides differentiation processes also cell movement. In the present review, the cDNAs encoding the following chemokines were described and the roles of their deduced proteins during self-self and nonself recognition outlined: the allograft inflammatory factor, the glutathione peroxidase, the endothelial-monocyte-activating polypeptide, the pre-B-cell colony-enhancing factor and the myotrophin as well as an enzyme, the (2-5)A synthetase, which is involved in cytokine response in vertebrates. A further step required to reach the evolutionary step of the integrated stage of the Urmetazoa was the acquisition of a stem cell system. In this review, first markers for stem cells (mesenchymal stem cell-like protein) as well as for chemokines involved in the maintenance of stem cells (noggin and glia maturation factor) are described at the molecular level, and a first functional analysis is approached. Taken together, it is outlined that the chemokine network was essential for the establishment of metazoans, which evolved approximately 600 to 800 million years ago.


Antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.
Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody titers of the IgG or IgA classes, and no bactericidal activity in vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation.


Research interests of family physicians applying for research training.
There is an ongoing need for research to support the practice of high quality family medicine. The Family Medicine Discovers Rapid Cycle Scientific Discovery and Innovation (FMD RapSDI) program is designed to build capacity for family medicine scientific discovery and innovation in the United States. Our objective was to describe the applicants and research questions submitted to the RapSDI program in 2019 and 2020. Descriptive analysis for applicant characteristics and rapid qualitative analysis using principles of grounded theory and content analysis to examine the research questions and associated themes. We examined differences by year of application submission and the applicant's career stage. Sixty-five family physicians submitted 70 applications to the RapSDI program; 45 in 2019 and 25 in 2020. 41% of applicants were in practice for five years or less (n = 27), 18% (n = 12) were in in practice 6-10 years, and 40% (n = 26) were ≥ 11 years in practice. With significant diversity in questions, the most common themes were studies of new innovations (n = 20, 28%), interventions to reduce cost (n = 20, 28%), improving screening or diagnosis (n = 19, 27%), ways to address mental or behavioral health (n = 18, 26%), and improving care for vulnerable populations (n = 18, 26%). Applicants proposed a range of research questions and described why family medicine is optimally suited to address the questions. Applicants had a desire to develop knowledge to help other family physicians, their patients, and their communities. Findings from this study can help inform other family medicine research capacity building initiatives.


Transcatheter aortic valve implantation in patients of small body size.
The aim of this study was to evaluate the efficacy and safety of transcatheter aortic valve implantation (TAVI) in patients of small body size (SB). Between October 2006 and November 2011, 424 patients undergoing TAVI were evaluated. Patients with a small body surface area (BSA; <1.75 m(2)) were defined as the "SB group" (n = 215) and the remaining large BSA patients as the "LB group" (n = 209). In the SB group, mean annulus diameter measured by CT and minimal femoral artery diameter were significantly smaller (23.1 ± 1.92 vs. 24.3 ± 1.91 mm, P < 0.01; 7.59 ± 1.06 vs. 8.29 ± 1.34 mm, P < 0.01, respectively). The logistic EuroSCORE was similar between groups (22.5 ± 10.4 vs. 23.4 ± 12.0; P = 0.43). Equivalent device success (91.2% vs. 91.4%; P = 0.94) and 30-day survival rates (85.1% vs. 87.6%; P = 0.46) were achieved in both groups. Vascular complications and the 30-day combined safety end point rate were significantly higher in the SB group (13.0% vs. 4.3%, P < 0.01; 27.4% vs. 18.3%, P = 0.03, respectively). Similar post-procedural mean pressure gradient was achieved in both groups (10.2 ± 4.3 vs. 11.0 ± 4.6 mmHg; P = 0.12). Multivariate analysis showed that BSA was one of the independent predictors of 30-day combined safety end point (Odds ratio: 0.20; 95% confidence interval (CI): 0.05-0.88; P = 0.03). However, Kaplan-Meier analysis revealed no significant difference in mid-term survival rate between groups (log-rank P = 0.64). TAVI in SB patients resulted in similar clinical outcomes with effective post-procedural hemodynamics compared with LB patients. Care should be taken to avoid vascular complications in SB patients.


Feasibility and limitations of C1 lateral mass screw placement in patients of atlas assimilation.
C1 lateral mass is a common place for screw fixation in normal anatomy; whereas there is no research about whether screw placement is suitable in patients of C1 assimilation (C1A). To study the feasibility and limitations of C1 lateral mass screw placement in patients with C1A. From April 2008 to March 2009, C1 lateral mass of 17 C1A patients with atlantoaxial instability (AAI) or dislocation (AAD) was observed and measured using CT reconstruction; and factors determining C1 lateral mass screw placement were studied before and during the operation. A screw of 3.5mm in diameter could be virtually inserted in 31 C1 lateral masses of total 17 C1A patients with maximal length of the screw 18.1±2.7mm; but the entry point of screw had to be modified in the posterior part of inferior facet of C1 instead of posterior middle wall of C1 lateral mass. Clinically, abnormal course of vertebral artery in 6 of 30 (20%) and abundance of venous plexi prevented the proper exposure of C1 lateral mass and screw placement. Hypoglossal canal also had potential risk of injury during screw placement. In patients of C1A, when C1 lateral mass screw placement is programmed, factors limit its use should be well studied, and CT angiography is essential.


Evaluation of low-dose dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in orthopedic surgeries: A prospective randomized double-blind study.
Neuraxial adjuants to local anesthetics is an effective technique of improving the quality and duration of postoperative analgesia. The safety and efficacy of drugs like dexmedetomidine and neostigmine as epidural medications have been sparsely investigated. Combined spinal-epidural anesthesia was performed in 60 American Society of Anesthesiologists I and II patients who required lower limb surgeries of ≤3 h duration. The epidural drug was administered at the end of surgery with patients randomized into three groups. Group I, II and III received 6 ml of 0.25% bupivacaine alone, with 1 ug/kg of neostigmine and with 0.5 ug/kg of dexmedetomidine + 1 ug/kg of neostigmine, respectively. The patients were prescribed 50 mg tramadol intravenous as rescue analgesic. Patients were assessed for hemodynamic parameters, pain scores, duration of analgesia, rescue analgesic requirements and the incidence of side-effects over the next 10 h. Data was analyzed using SPSS(®) version 17.0 (Chicago, IL, USA). P < 0.05 was considered as statistically significant. Patients in Group III had significantly longer mean duration of analgesia (273.5 min) compared to Group II (176.25 min) and Group I (144 min). There was increased requirement of fluids to maintain blood pressures in Group III. Neostigmine did not cause significant incidence of gastrointestinal side effects. Epidurally administered dexmedetomidine and neostigmine exhibit synergism in analgesic action. The incidence of drug-related side-effects was low in our study.


Responses of fowls to an operant feeding procedure and its potential use for reducing randomness in meal occurrence.
Adult laying hens were tested with increasing and decreasing procurement costs (pecks at a disc) which allowed access to food for unlimited periods. This was done to observe changes in feeding behaviour, to see whether apparent randomness in meal occurrence can be reduced, and, if so, to identify an appropriate fixed ratio (FR) for incorporating in investigations of physiological correlates of hunger and satiety. Daily food intake stayed the same at all but the highest (160 pecks) FR. FR sizes were related negatively to total time feeding and meal frequency, and positively to intermeal interval length, meal size and rate of eating within meals. They were also related positively to meal length, but only weakly so. Frequency distributions of meal and interval lengths, and postprandial correlation coefficients, indicated that randomness in feeding did decline at higher FRs, and FR20 seems the most appropriate schedule for potential use in physiological experiments.


Activity enhancement pathways in LaFeO3@TiO2 heterojunction photocatalysts for visible and solar light driven degradation of myclobutanil pesticide in water.
LaFeO3@TiO2 heterojunction composites with a core-shell porous structure and LaFeO3 contents in the 2.5-25 wt.% range have been synthesized via consecutive sol-gel syntheses and tested for the photocatalytic oxidation of the myclobutanil pesticide in water under solar light and pure visible light. Whatever the light spectrum, the kinetic rate constants for both myclobutanil degradation and TOC conversion exhibited a volcano-like profile with increasing the narrow band-gap (2.1 eV) LaFeO3 content, the optimum composite strongly overperforming both single phases, with full myclobutanil mineralization achieved in 240 min in the best case. The light spectrum influenced the optimum LaFeO3 content in the composite, being observed at 5 wt.% and 12.5 wt.% under solar and visible light, respectively. This has been attributed to the existence of different light-mediated reaction mechanisms. The optimum LaFeO3/TiO2 composite photocatalyst was active and stable after several runs under solar light with leached iron concentration below 0.1 mg/L in solution.


Effect of age, dose and antibiotic therapy on the development of Clostridium difficile infection in neonatal piglets.
Piglet diarrhea is associated with increased pre-weaning mortality, poor growth rates, and variation in weight at weaning. Clostridium difficile is a known cause of enteric disease in neonatal piglets, yet risk factors associated with C. difficile infection in piglets are unknown. The objectives of this study were (1) to evaluate the consistency and severity of lesions in piglets challenged with C. difficile at different bacterial doses (DOSAGE experiment), (2) evaluate the use of antibiotics as a contributing risk factor in 1-day-old piglets (ANTIMICROBIAL experiment), and (3) to provide a clinical and histological evaluation of C. difficile infection in 10-day-old piglets (AGE experiment). One hundred and eleven conventional neonatal pigs were snatch farrowed and divided into experimental groups addressing the objectives. In the DOSAGE experiment, 40 1-day-old piglets were sham inoculated or challenged with varying amounts of C. difficile heat shocked spores and euthanized 72 h post infection. Results indicate a clear trend for disease development as bacterial numbers increase. In the ANTIMICROBIAL experiment, 39 1-day-old piglets were challenged and then treated with one of four different antibiotics after 16 h. No significant difference in disease development was found. Thirty-three 10-day-old piglets were given varying doses of C. difficile in the AGE experiment. Disease and lesions were reproduced in 10-day-old piglets. Combined results indicate that C. difficile dosage appears to be an important factor that influences the appearance and severity of lesions, 10-day-old pigs can develop disease associated with C. difficile, and antibiotic administration following inoculation may not be a major contributor for disease in neonatal piglets.


Unprecedented pairs of uranium (iv/v) hydroxido and (iv/v/vi) oxido complexes supported by a seven-coordinate cyclen-anchored tris-aryloxide ligand.
We present the synthesis and reactivity of a newly developed, cyclen-based tris-aryloxide ligand precursor, namely cyclen(Me)( t-Bu,t-BuArOH)3, and its coordination chemistry to uranium. The corresponding uranium(iii) complex [UIII((OAr t-Bu,t-Bu)3(Me)cyclen)] (1) was characterized by 1H NMR analysis, CHN elemental analysis and UV/vis/NIR electronic absorption spectroscopy. Since no single-crystals suitable for X-ray diffraction analysis could be obtained from this precursor, 1 was oxidized with methylene chloride or silver fluoride to yield [(cyclen(Me)( t-Bu,t-BuArO)3)UIV(X)] (X = Cl (2), F (3)), which were unambiguously characterized and successfully crystallized to gain insight into the molecular structure by single-crystal X-ray diffraction analysis (SC-XRD). Further, the activation of H2O and N2O by 1 is presented, resulting in the U(iv) complex [(cyclen(Me)( t-Bu,t-BuArO)3)UIV(OH)] (4) and the U(v) complex [(cyclen(Me)( t-Bu,t-BuArO)3)UV(O)] (6). Complexes 2, 3, 4, and 6 were characterized by 1H NMR analysis, CHN elemental analysis, UV/vis/NIR electronic absorption spectroscopy, IR vibrational spectroscopy, and SQUID magnetization measurements as well as cyclic voltammetry. Furthermore, chemical oxidation of 3, 4, and 6 with AgF or AgSbF6 was achieved leading to complexes [(cyclen(Me)( t-Bu,t-BuArO)3)UV(F)2] (5), [(cyclen(Me)( t-Bu,t-BuArO)3)UV(OH)][SbF6] (7), and [(cyclen(Me)( t-Bu,t-BuArO)3)UVI(O)][SbF6] (8). Finally, reduction of 7 with KC8 yielded a U(iv) complex, spectroscopically and magnetochemically identified as K[(cyclen(Me)( t-Bu,t-BuArO)3)UIV(O)].


The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions.
Perioperative factors including hypoxia, hypocapnia, and certain anesthetics have been suggested to contribute to Alzheimer disease (AD) neuropathogenesis. Desflurane is one of the most commonly used inhalation anesthetics. However, the effects of desflurane on AD neuropathogenesis have not been previously determined. Here, we set out to assess the effects of desflurane and hypoxia on caspase activation, amyloid precursor protein (APP) processing, and amyloid beta-protein (Abeta) generation in H4 human neuroglioma cells (H4 naïve cells) as well as those overexpressing APP (H4-APP cells). Neither 12% desflurane nor hypoxia (18% O(2)) alone affected caspase-3 activation, APP processing, and Abeta generation. However, treatment with a combination of 12% desflurane and hypoxia (18% O(2)) (desflurane/hypoxia) for 6 h induced caspase-3 activation, altered APP processing, and increased Abeta generation in H4-APP cells. Desflurane/hypoxia also increased levels of beta-site APP-cleaving enzyme in H4-APP cells. In addition, desflurane/hypoxia-induced Abeta generation could be reduced by the broad caspase inhibitor benzyloxycarbonyl-VAD. Finally, the Abeta aggregation inhibitor clioquinol and gamma-secretase inhibitor L-685,458 attenuated caspase-3 activation induced by desflurane/hypoxia. In summary, desflurane can induce Abeta production and caspase activation, but only in the presence of hypoxia. Pending in vivo confirmation, these data may have profound implications for anesthesia care in elderly patients, and especially those with AD.


Clonidine suppresses the induction of long-term potentiation by inhibiting HCN channels at the Schaffer collateral-CA1 synapse in anesthetized adult rats.
Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1 mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats. Clonidine (1.25, 2.5 μg/kg, icv, 10 min before HFS) also dose-dependently inhibited synaptic plasticity, which had no remarkable effect on HR and aortic pressure. But, 20 min after HFS, administration of clonidine (2.5 μg/kg) had no effect on LTP. The inhibitory effect of clonidine (2.5 μg/kg) on LTP was completely reversed by yohimbine (18 μg/kg, icv) and ZD7288 (5 μg/kg, icv). Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 μM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 μM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 μM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer collateral-CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.


Adverse Childhood Experiences and School Readiness Among Preschool-Aged Children.
To examine the association between preschool-aged children's exposure to adverse childhood experiences (ACEs) and multiple, intersecting domains of school readiness using a nationally representative sample. A sample of 15 402 preschool-aged children (3-5 years) in the US from the 3 most recent cohorts (2016-2018) of the National Survey of Children's Health were employed. Primary caregivers were asked survey questions about the adversities experienced by focal children. Four distinct domains of school readiness among the children were also derived from the survey: early learning skills, self-regulation, social-emotional development, and physical health and motor development. Although nearly one-half of children who had not been exposed to ACEs were on-track across all domains, only 1 in 5 children exposed to 3 or more ACEs were on-track across all domains. Follow-up analyses identified parenting stress and reduced positive parenting practices as significant mediators of this association. Multivariate results also indicated that, regardless of the school readiness domain examined, an accumulation of ACEs increased the rate of items on which a child needs support or is at-risk. An accumulation of ACEs among preschool-aged children elevates risk within and across school readiness domains. These findings highlight the urgent need to identify best practices to reduce ACE exposure, as well as improve school readiness during early childhood.


Endovascular treatment of spinal vascular malformations.
Endovascular treatment is considered as the first choice of treatment for most cases of spinal vascular malformations. Clinical presentation, natural history, and origin of symptoms are briefly described on spinal cord arteriovenous malformations, spinal dural arteriovenous fistulas, epidural fistulas, and paraspinal fistulas. Pretherapeutic evaluation, materials and technique for embolization, post-therapeutic management, results, and follow-up are discussed for each disease.


Research Progress in the Field of Gambogic Acid and Its Derivatives as Antineoplastic Drugs.
Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.


The effects of hypnosis on anxiety, depression, fatigue, and sleepiness in people undergoing hemodialysis: a clinical report.
This study investigated the effect of hypnosis on anxiety, depression, fatigue, and sleepiness in hemodialysis patients. Twenty-nine patients participated in the 15-day study. A single hypnosis session was performed on Day 8. Anxiety, depression, fatigue, and sleepiness were measured at baseline, on Day 8, and on Day 15 (HADS, MFI, ESS). Daily fatigue was also measured numerically. Anxiety, depression, and sleepiness significantly decreased after hypnosis. Weekly measures of fatigue remained stable; however, daily fatigue decreased.


Let's quit stalling and do program evaluation.
Five issues have been identified as major impediments to program evaluation. Examination of these issues shows many of them to be resolved in the process of conducting evaluations. It is asserted that only by implementing evaluations will the field move foreward. At the present time much energy is wasted discussing or arguing the five issues and the ideal approach to making program evaluations. Examples are provided from ongoing evaluations that show how the issues are resolved.


Analysis of perfluorooctane sulfonate and perfluorooctanoic acid with a mixed-mode coating-based solid-phase microextraction fiber.
A novel mixed-mode coating-based solid-phase microextraction (SPME) fiber was prepared by chemical bonding dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride and 3-(trimethoxysilyl)-1-propanamine, the sol-gel precursors, on an anodized Ti wire, aiming to effectively adsorb perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). The anodized Ti wire with uniform TiO2 nanotube arrays provides high mechanical strength and strong adhesion to the mixed-mode coating. The prepared fiber shows excellent organic solvent stability due to the covalent bonding between the coating and the fiber, and significantly higher extraction efficiency than the commercial fibers, 100 μm polydimethylsiloxane and 85 μm polyacrylate fiber, due to the synergistic extraction effects of the coating functional groups. Good linearity (R(2)=0.9994 for PFOS, R(2)=0.9992 for PFOA) was obtained with detection limits of 2.5 and 7.5 pg mL(-1) for PFOS and PFOA, respectively. Recoveries were in the range of 88%-102%. The proposed method was successfully applied in the analysis of PFOS and PFOA in a local river with the results of 0.05 and 0.06 ng mL(-1), respectively.


Diagnosis of acute cholecystitis in patients with liver cirrhosis: waveform analysis of the cystic artery by color Doppler imaging.
The aim of this study was to investigate the possibility of diagnosing acute cholecystitis in patients with liver cirrhosis using color Doppler imaging to demonstrate the hemodynamics. Color Doppler imaging was used to analyze the waveform of the cystic artery in 28 cirrhotic subjects with thickened gallbladder walls and 56 normal controls. The cirrhotic group was further divided into the cholecystitis group, containing 6 cirrhotic patients with acute cholecystitis, and the liver cirrhosis group, containing 22 cirrhotic patients without acute cholecystitis. Maximum velocity (Vmax) was significantly higher in the cholecystitis group (31.6 ± 23.0 cm/s) than in the normal controls (16.1 ± 5.9 cm/s) (P < 0.01). The resistance index (RI) was higher in the liver cirrhosis group (0.84 ± 0.04) than in either the normal controls (0.70 ± 0.06) (P < 0.01) or the cholecystitis group (0.72 ± 0.09) (P < 0.01). Sensitivity and specificity were 100% when the diagnostic criteria of acute cholecystitis were a maximum velocity of more than 40 cm/s, a resistance index of more than 0.75, or both. A pulsatile signal with a maximum velocity of more than 40 cm/s, a resistance index lower than 0.75, or both indicated the presence of acute cholecystitis in patients with liver cirrhosis and a thickened gallbladder wall.


[The effect of nerve growth factor, guanethidine and their combined use on nuclease activity in animal tissues].
Activity of ribo- and deoxyribonucleases RNAases I and II, DNAases I and II was studied in brain hemispheres, liver, kidney and heart tissues of one-month-old rats, which were administered daily, beginning from birth either with nerve growth factor 15 micrograms/kg, guanethidine 30 micrograms/kg or with these compounds simultaneously at the doses mentioned above. Activity of the nucleases studied was altered in nervous tissue and in vegeto-dependent tissues after separate treatment with both nerve growth factor and guanethidine, while their simultaneous administration caused slight normalization but not to complete recovery of the patterns studied.


Haemorrhagic shock-encephalopathy syndrome: plasmapheresis as a therapeutic approach.
We present the case of a 4.5-week-old boy with acute encephalopathy, shock, intestinal bleeding and disseminated intravascular coagulation. The clinical course and typical laboratory parameters were compatible with a diagnosis of haemorrhagic shock-encephalopathy syndrome (HSE). Immediate shock treatment, repeated haemodialysis and plasmapheresis did not prevent a fatal outcome 4 days after the onset of clinical symptoms.


The risks of major head and neck surgery in the aged population.
A review of 162 major head and neck operative cases for cancer in patients over age 70 from 1963-1973 are reviewed. The major and minor surgical complication rates and the rate of medical complications are compared to 552 similar procedures in patients under age 70, during the same time period. The operative mortality figures for each group, as well as the causes of death, are examined. A plea is made for aggressive therapy in the elderly, both in the surgical planning and in their pre- and postoperative care.


Simultaneous determination of 9-ethylphenanthrene, pyrene and 1-hydroxypyrene in an aqueous solution by synchronous fluorimetry using the double scans method and hydroxyl-propyl beta-cyclodextrin as a sensitizer.
A novel method for the simultaneous determination of 9-ethylphenanthrene (9-EP), pyrene (Pyr) and 1-hydroxypyrene (1-OH-Pyr) in an aqueous solution using hydroxyl-propyl β-cyclodextrin (HPCD) as a sensitizer has been established. The overlap of the conventional fluorescence spectra of these molecules is resolved using synchronous fluorescence spectrometry with the double scans method. The simultaneous quantitative determination of three compounds was carried out with Δλ=36 nm and Δλ=55 nm. The signals detected at these three wavelengths (i.e., 298 nm, 337 nm and 351 nm) vary linearly when the concentrations of 9-EP, Pyr and 1-OH-Pyr were in the range of 5.00×10(-8)-1.60×10(-6) mol L(-1), 2.00×10(-8)-1.80×10(-6) mol L(-1), and 2.00×10(-8)-1.20×10(-5) mol L(-1), respectively. The limits of detection (LOD) for 9-EP, Pyr and 1-OH-Pyr were 3.97×10(-9) mol L(-1), 5.25×10(-)(9) mol L(-1), 4.20×10(-9) mol L(-1), respectively, with relative standard deviations (R.S.D.) of 1.62%, 2.45% and 1.73% (n=9), respectively. The inclusion behaviors between HPCD and the guest molecules were observed by synchronous fluorimetry and the association constants for the 1:1 complexes with HPCD were determined. The binding and complexation energies for different orientations are discussed. The proposed method was successfully applied to the analysis of 9-EP, Pyr and 1-OH-Pyr in tap and lake water with good recoveries in the range of 92.9-110.0%.


Pharmacokinetics and bioavailability of ST 1435 administered by different routes.
The ovulation inhibiting potency of the synthetic progestin ST 1435 (Nestorone) is high after parenteral administration and practically nil after oral administration. The purpose of this study was to determine the pharmacokinetic parameters of ST 1435 after single oral or intravenous administration or after long-term treatment with subdermal implants in women. After administration, as a single i.v. bolus, the plasma disappearance rate of immunoreactive ST 1435 had two components with half-lives (mean +/- SE) of 3.5 +/- 0.5 and 83 +/- 14 min, respectively. The volume of distribution was 4.7 +/- 1.3 L/Kg and the metabolic clearance rate was 55 +/- 6 L/Kg/d. After oral administration, the bioavailability was about 10% of the dose. After chronic subdermal administration, the plasmatic clearance was slower than following the acute doses. These results show that ST 1435 has shorter half-lives and a faster clearance rate than progestins which bind SHBG. The large volume of distribution indicates accumulation in the extravascular space and was expected in view of the high affinity of ST 1435 for progesterone receptors. The slower plasma elimination rate after chronic administration was attributed to the re-entry of a larger mass of drug from the extravascular space, and/or accumulation of immunoreactive metabolites with slower clearance than the parent steroid.


Myxoid intraneural cysts of external popliteal ischiadic nerve. Report of 2 cases studied with ultrasound, computed tomography and magnetic resonance imaging.
Peripheral neuropathy of the external popliteal ischiadic nerve caused by intraneural cysts is a very rare and peculiar pathological phenomenon compared with diseases associated with extraneural cysts or colliquative phenomena of solid nervous lesions. Two cases of peripheral neuropathy of the external popliteal ischiadic nerve caused by intraneural cysts and evaluated with ultrasound, computed tomography and magnetic resonance are described. The diagnostic efficacy of these imaging modalities is also evaluated with particular reference to MR capability to define the morphology of such lesions and their relationships to the surrounding structures. It is not yet possible to obtain a correct diagnosis about histopathologic features by means of the imaging techniques currently available. Nevertheless, they do provide information about the involvement of the neighboring areas, which are useful indications for possible surgical treatment of the disease.


Household waste management in Singapore and Shanghai: Experiences, challenges and opportunities from the perspective of emerging megacities.
Due to rapid economic development and urbanisation, emerging megacities with dense populations have witnessed a significant increase in waste generation. Megacities face challenges in developing sustainable waste management systems. Considerable heterogeneity exists across megacities in management strategies. The two selected emerging megacities, Singapore (a city-state) and Shanghai, have similar developmental characteristics, but their waste management modes differ strikingly. This study assessed the two modes in terms of management strategies, environmental effects, economic costs, and social outcomes. Environmental footprint analysis and cost quantification were employed for the assessment based on public data. The research results would permit a deeper understanding of the long-term sustainability of each mode while considering the feasibility of implementation across different contexts. It was found that the waste management system in Singapore had a relatively lower environmental impact than Shanghai before Shanghai's new waste segregation and recycling policy in 2019. However, when the effect of fossil fuel substitution is taken into account, the environmental burden in Shanghai can be lowered more substantially than the one in Singapore. Although Shanghai had more economic burden for the waste segregation at source, it tended to implement the circular economy principles (e.g., reduce, reuse, and recycling) better and improve its sense of community significantly. Based on the practical experiences from the two representative megacities, suggestions for better waste management practices were provided for Singapore, Shanghai, and other emerging megacities with similar circumstances. In addition, challenges and opportunities related to household waste segregation and recycling were identified to guide future practices in emerging megacities.


Early Intervention With a Curative Intent Through an Intensive Therapy Versus Immunologic Disease Control Using a Minimal Intensity Approach in the Management of High-risk Smoldering Multiple Myeloma: A Systematic Review of Evidence From Clinical Trials.
A subset of individuals with smoldering myeloma (SMM) are at a high risk of progression to symptomatic myeloma. Current efforts are focused on identifying this high-risk group and intercepting the disease process before its progression. There is no consensus on what the goal of an intervention should be, whether to aim for a cure through a high-intensity intervention or pursue immunologic disease control using the least intense approach. This systematic review summarized current evidence in support of the optimum approach. A database search of Medline/PubMed, Scopus, EMBASE, Web of Science, CINAHL, Wiley Cochrane Library, clinicaltrials.gov, and conference proceedings of ASH, EHA, ASCO, ESMO was performed. Results were presented using narrative synthesis of quantitative data. Of the 2088 identified records, a total of 10 eligible studies made up of 6 minimal-intensity clinical trials, 3 moderate-intensity trials, and 1 high-intensity trial were included in this review with a total demographic population of 588 high-risk SMM patients. Minimal intensity lenalidomide-based regimen demonstrated clinical effectiveness in delaying disease progression and improving overall survival in high-risk SMM. The single-agent monoclonal antibodies did not have any major impact on improving overall survival, although the studies were not powered to do so. There is a marked increase in the depth of response as the intensity of treatment increases without a proportional improvement in overall survival. Moderate- and high-intensity interventions yielded similar minimal residual disease negativity rates and overall survival. The minimal, moderate, and high-intensity approaches all demonstrated clinical benefits in delaying disease progression and improving overall survival in patients with high-risk SMM and increasing intensity of intervention does not necessarily translate to improved overall survival.


Development and validation of a multivariable preoperative prediction model for postoperative length of stay in a broad inpatient surgical population.
Postoperative length of stay is a meaningful patient-centered outcome and an important determinant of healthcare costs. The Surgical Risk Preoperative Assessment System preoperatively predicts 12 postoperative adverse events using 8 preoperative variables, but its ability to predict postoperative length of stay has not been assessed. We aimed to determine whether the Surgical Risk Preoperative Assessment System variables could accurately predict postoperative length of stay up to 30 days in a broad inpatient surgical population. This was a retrospective analysis of the American College of Surgeons' National Surgical Quality Improvement Program adult database from 2012 to 2018. A model using the Surgical Risk Preoperative Assessment System variables and a 28-variable "full" model, incorporating all available American College of Surgeons' National Surgical Quality Improvement Program preoperative nonlaboratory variables, were fit to the analytical cohort (2012-2018) using multiple linear regression and compared using model performance metrics. Internal chronological validation of the Surgical Risk Preoperative Assessment System model was conducted using training (2012-2017) and test (2018) datasets. We analyzed 3,295,028 procedures. The adjusted R2 for the Surgical Risk Preoperative Assessment System model fit to this cohort was 93.3% of that for the full model (0.347 vs 0.372). In the internal chronological validation of the Surgical Risk Preoperative Assessment System model, the adjusted R2 for the test dataset was 97.1% of that for the training dataset (0.3389 vs 0.3489). The parsimonious Surgical Risk Preoperative Assessment System model can preoperatively predict postoperative length of stay up to 30 days for inpatient surgical procedures almost as accurately as a model using all 28 American College of Surgeons' National Surgical Quality Improvement Program preoperative nonlaboratory variables and has shown acceptable internal chronological validation.


[Problems in the prenatal diagnosis of fetal microcephaly].
By the example of a case of lissencephalia the problems of prenatal diagnosis of the very rare, genuine fetal microcephalia are demonstrated: differentiation to pseudomicrocephalia, vague to missing midline echo, lacking possibility of radiological objectification.


Discovery of anti-neuroinflammatory agents from 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives by regulating microglia polarization.
Neuroinflammation mediated by microglia activation leads to various neurodegenerative and neurological disorders. In order to develop more and better options for this disorders, a series of 3,4-dihydrobenzo[b]oxepin-5(2H)-one derivatives (BZPs, 6-19) and novel 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives (BPMs, 20-33) were synthesized and screened the anti-neuroinflamamtion effects. 3,5-bis-trifluoromethylphenyl-substituted BPM 29 showed more potent anti-neuroinflammatory activity and no toxicity to BV2 microglia cells in vitro. 29 significantly reduced the number of M1 phenotype of microglia cells, but significantly increased the number of M2 phenotype of microglia cells in lipopolysaccharide (LPS)-induced BV2 microglia cells. 29 significantly reduced the secretion of inflammatory cytokines (IL-18, IL-1β, TNF-α), but increased the secretion of anti-inflammatory cytokines (IL-10) from LPS-induced BV2 microglia cells. Also, 29 inhibited the NOD-like receptor NLRP3 inflammasome formation, and down-regulated the expression of M2 isoform of pyruvate kinase in LPS-induced BV2 microglia cells. In vivo, 29 reduced the neuroinflammation in cuprizone-induced inflammatory and demyelinating mice by reducing the expression of inducible nitric-oxide synthase, but increased the expression of CD206. Taken together, 29 might be a prospective anti-neuroinflammatory compound for neuroinflammatory and demyelinating disease by alleviating microglia activation.


Evaluation of commercial immunoperoxidase kits in diagnosis of prostate carcinoma.
Comparison of one commercial immunoperoxidase kit for prostate specific acid phosphatase (PSAP) and two for prostate specific antigen (PA) with an unlabelled antibody peroxidase-antiperoxidase (PAP) technique using rabbit antihuman PSAP revealed generally good reproducibility of results on formalin-fixed, paraffin-embedded sections of primary and metastatic prostatic carcinoma. Frequency of positivity was 92 per cent with both our noncommercial PAP and the kit method for PSAP, and 82 per cent and 89 per cent with kits for PA. Thus, sensitivity with the PA kits was less than with our noncommercial PAP and the kit PSAP, with less intense immunostain and occasional false negatives. Specificity was good with all three kits, and no false positive results were obtained. Commercial immunoperoxidase kits provide a relatively easy and inexpensive means for practicing pathologists in a service-oriented setting to make more precise diagnoses in cases of poorly differentiated or metastatic carcinoma of prostatic origin.


The crystal sheaths from bivalve hinge ligaments.
The aragonite crystals in the molluscan bivalve hinge ligament are surrounded by an organic sheath which is distinct from the remainder of the ligament matrix. Methods have been developed to isolate these sheathed crystals from the ligaments of Spisula solidissima and Mercenaria mercenaria employing a papain digestion of the matrix protein. The sheathed crystals from Spisula have a CaCO3/protein ratio of 11.1 and those from Mercenaria a ratio of 29.6. The sheathed crystals and the empty crystal sheaths have been examined by electron microscopy for structural integrity. The sheath proteins exhibit much smaller proportions of the amino acids glycine and methionine than the hinge ligaments. These are characteristic amino acids of high concentrations in the hinge ligaments of both species. The concentrations of acidic and basic amino acids are increased about two fold in the sheaths over those of the ligaments. Otherwise there is little similarity in the amino acid composition of the sheaths in the two species. However, SDS electrophoresis shows the sheaths of both to contain a major protein component with a molecular weight of about 25,000. The sheath protein from the Mercenaria ligament contains about 5% carbohydrate and that of Spisula sheaths less than 1% carbohydrate.


Identification of hibernating myocardium by dobutamine stress echocardiography: comparison with thallium-201 reinjection imaging.
The aim of this study was to determine the diagnostic value of dobutamine stress echocardiography (DSE) in the identification of hibernating myocardium and to compare its predictive accuracy with that of thallium-201 reinjection (RI) imaging. The subjects were 26 patients with wall motion abnormalities related to stenosed coronary arteries. DSE predicted postrevascularization improvement in 31 of 33 segments that were considered to be hibernating and identified 8 of 10 nonhibernating segments. In contrast, thallium-201 scintigraphy predicted all 33 hibernating segments when a post-RI myocardial thallium uptake in ischemic areas of > or = 50% of the maximum count in normal segments was used as a positive marker of myocardial viability. However, thallium studies predicted only 30 of 33 hibernating segments when thallium redistribution (RD) was used as a marker of viability in delayed or RI images. Among the 10 nonhibernating segments, an uptake of < 50% was observed in 4 segments and negative thallium-201 RD was observed in 5 segments. The sensitivity, specificity, and predictive values (PV) of DSE were 94%, 80%, positive PV 94%, and negative PV 80%, respectively. In contrast, the sensitivity, specificity, and PV of thallium-201 RI imaging were 100%, 40%, 85%, and 100% with uptake > or = 50% and 91%, 50% 86%, and 63% with RD, respectively. These results suggest that DSE may be useful for identifying hibernating myocardium and could therefore be helpful in selecting candidates for coronary revascularization.


Carbamazepine and cardiac conduction disturbances.
Carbamazepine-induced cardiac conduction disturbance is reported in 2 patients suffering from epilepsy. The cardiac defects disappeared in both patients after carbamazepine was discontinued, and reappeared in 1 patient after treatment was resumed.


Histopathological parameters as predictors for the course of Crohn's disease.
Recent classification systems discriminate penetrating Crohn's disease (CD) from stricturing and non-stricturing/non-penetrating CD. As yet, no easily detectable marker is known that can predict the course of CD. Individual, clinical course-specific new treatment schemes would be highly desirable for different potentially divergent pathophysiological pathways (e.g., fistula vs stenosis). Intestinal tissue biopsies from 63 CD patients with a disease follow-up of up to 7 years were studied retrospectively. In biopsy specimens, 34 histopathological features present prior to the onset of (a) strictures or (b) fistulas were evaluated and compared with biopsies from patients with non-stricturing/non-penetrating disease. Five histomorphological parameters demonstrated significant associations to different disease courses when applying univariate analysis. In a multivariate logistic regression model (1) severe lymphocytic infiltration of the lamina propria, (2) presence of crypt atrophy, and (3) absence of lymphocytic infiltration of the epithelium are the best variables to predict an uncomplicated disease course (Nagelkerke R2=0.329; P=0.001). The combination of these parameters has a sensitivity of 67% and a specificity of 83% to predict non-stricturing/non-penetrating disease (positive predictive value=0.75). Histopathological parameters may help to predict complications of CD prior to their onset. The results of this study have to be confirmed prospectively.


A solid-state NMR study of protein hydration and stability.
The mobility of protein in powders at different hydration levels was studied in relation to aggregation and activity. Magic angle spinning 13C, 15N, 1H, 2H, and 17O NMR techniques were used to determine changes in the mobility of surface residues in proteins as a function of hydration and related to changes in activity. NMR relaxation measurements of high frequency (omega0, T1) and low frequency (omega1,T1p) motions have been carried out on lyophilized DNase, insulin and lysozyme stored at different relative humidities. Moisture-induced aggregation and enzymatic activity of the lyophilized proteins was determined by high performance size exclusion chromatography and bioassays. There was little change in T1p observed with increasing humidity. The results show, however, that there is a decrease in T1 for DNase, insulin and lysozyme at relative humidities ranging from 0-98%, and we propose that the reduction in T1 is related to the aggregation susceptibility of proteins during storage at different humidities. The water mobility was determined directly using 17O NMR experiments. We found that as the amount of weakly-bound water increases, the protein surface mobility decreases and is coupled with increased aggregation. Aggregation measurements at different humidities were correlated with bioassays for lysozyme and found to be consistent with the hydration data. Mobility of protein molecules was determined by solid-state NMR over a wide range of % RH and it was found that water content leads to a change in mobility of protein molecules. The aggregation and activity of proteins were strongly correlated to change in molecular mobility.


Are increases in COP variability observed when participants are provided explicit verbal cues prior to COM stabilization?
Previous research has shown that when the COM is stabilized without participant awareness, COP displacements increase. This finding suggests that postural sway under normal conditions may be exploratory and used as a means of acquiring sensory information. However, based on the theory that posture is controlled using internal models, it could be argued that increases in COP displacement reflect errors that arise as the central nervous system attempts to adapt the internal model used to control posture to the new conditions. The current study provided an explicit verbal cue to the participants indicating how and when COM stabilization would occur. Based on evidence suggesting that explicit verbal cues can reduce errors when the dynamics of the task are altered, we hypothesized that when participants were aware of COM stabilization, COP displacements would be reduced. However, we found that anterior-posterior COP displacements increased independent of cueing, suggesting that increases in COP displacements with locking were not the result of an attempt to adapt the internal model of postural control. The results provide further support for an exploratory role of postural sway.


Effects of PACAP on survival and renal morphology in rats subjected to renal ischemia/reperfusion.
Pituitary adenylate cyclase activating polypeptide (PACAP) occurs and exerts a variety of biological functions in the nervous system and in the peripheral organs, including the urinary system. PACAP has protective effects against myeloma kidney injury and renal ischemia. Ischemia/reperfusion injury of the kidney is a major clinical problem, and based on the protective effects of PACAP in cerebral and cardiomyocyte ischemia, the aim of the present study was to evaluate the effects of a single intravenous PACAP injection on the survival and renal morphology after varying times of ischemia. Rats were subjected to renal artery clamping for 15, 30, 45, 60, or 75 min followed by reperfusion. PACAP (100 microg) was administered intravenously before arterial clamping. We found that a 15- or 30-min renal ischemia led to no renal dysfunction, and the kidneys showed normal appearance with no difference between PACAP- and saline-treated groups. Control rats with 45 min of ischemia had increased premature death rate and showed multifocal acute tubular atrophy, while a 60-min ischemia led to death of all control animals within a few days displaying severe, multifocal Grade II tubular atrophy. In contrast, all PACAP-treated animals survived with subtle morphological changes after the 45-min ischemia. After the 60-min ischemia, death rate was significantly lower in PACAP-treated rats compared to controls, and animals showed subtle focal tubular alteration. A 75-min ischemia was not performable in controls because of deaths before the termination of ischemia. PACAP-treated rats survived longer, but they also died after 5-10 days exhibiting severe focal tubular atrophy. In summary, our results clearly show that PACAP is able to prolong the renal ischemic time, decrease mortality, and attenuate tubular degeneration after renal ischemia.


Childhood Poisoning During the COVID-19 Pandemic.
To determine changes caused by the effect of the COVID-19 pandemic by examining the children admitted to our hospital because of poisoning during the pandemic and comparing these with data from a study conducted in the pre-pandemic period. A retrospective examination was made of children who were admitted to our pediatric emergency department with poisoning between March 2020 and March 2022. Of the 82 (0.7%) patients admitted to the emergency department, 42 (51.2%) were girls, the mean age was 6.43 ± 5.62 years, and the majority of children (59.8%) were under 5 years of age. The poisonings were determined to be accidental in 85.4% of cases, 13.4% were suicide attempts, and 1.2% were iatrogenic. Poisonings occurred most frequently (97.6%) at home and most frequently (85.4%) by digestive tract. The most common causative agent (68%) was non-pharmacological agents. Caustic-corrosive substances were determined in 39% of cases, medical drugs in 32%, toxic gases in 11%, alcohol (hand sanitizers) in 8.5%, insecticide-pesticide in 6.1%, food in 1.2%, and animal bites in 1.2%. Compared to the study conducted in our hospital in 2013-2014, the difference in terms of factors causing poisoning was statistically significant (P < .001). Of the current study cases, 14 (17.1%) were followed up in the intensive care unit, and no mortality developed. The period of the COVID-19 pandemic was seen to cause an increase in poisoning rates with caustic-corrosive substances, alcohol (hand disinfectants), and toxic gases. Families should be made aware of this issue and take special precautions.


Association of perfluoroalkyl substances exposure with reproductive hormone levels in adolescents: By sex status.
Polyfluoroalkyl substances (PFASs) are a group of common chemicals that ubiquitously exist in wildlife and humans. However, few studies have researched the effect of PFASs on reproductive hormones in adolescents. To provide information in this regard, we recruited 225 Taiwanese adolescents aged 13-15years from 2009 to 2010 to investigate the relationship between serum PFASs (PFOS, PFOA, PFBS, PFDA, PFDoA, PFHxA, PFHxS, PFNA and PFTA) and reproductive hormone concentrations using a cross-sectional study design. Results showed PFOS and PFTA levels were highest among the PFASs, with a median concentrations of 29.9 (interquartile range: 13.0-43.8) ng/mL and 6.0 (0.6-25.9) ng/mL in males, and a median concentrations of 28.8 (14.8-42.6) ng/mL and 4.5 (0.3-18.4) ng/mL in females. After adjustment for confounding factors, nonsignificant associations between PFASs and reproductive hormone were found except for PFNA with ln(estradiol) (β=0.2060, 95%CI: 0.0016, 0.4105). When stratified by sex, more significant associations were found in males than in females. Among males, PFASs were negatively associated with ln(testosterone) level for PFOS (β=-0.0029, 95%CI: -0.0055, -0.0003), PFDA (β=-0.2565, 95%CI: -0.4135, -0.0994), PFHxA (β=-0.3095, 95%CI: -0.5942, -0.0248), and PFNA (β=-0.4233, 95%CI: -0.6998, -0.1467). Furthermore, male participant ln(estradiol) levels were positively associated with PFOA (β=0.0921, 95%CI: 0.0186, 0.1656), and PFHxS (β=0.0462, 95%CI: 0.0020, 0.0905). Among females, a significant relationship was found only for PFDoA with ln(testosterone) (β=-0.0119, 95%CI: -0.0227, -0.0010). In conclusion, this study showed higher levels of PFASs coincide with lower testosterone and higher estradiol levels, and more significant associations of PFASs with reproductive hormone were found in males than in females.


Rapamycin and cyclosporine have different effects on expression of Ang-1 and Ang-2 and Tie2 in rat renal allograft with chronic allograft nephropathy.
Previous studies have indicated that angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) and tyrosine kinase receptor Tie2 regulate the maintenance and integrity of blood vessels and have potential anti-inflammatory properties. This study of cardiac allografts investigated whether there is a difference between rapamycin and cyclosporine A (CsA) in the ability to affect expression of Ang1, Ang2, and Tie2 in rat renal allografts with chronic allograft nephropathy (CAN). A male inbred F344 to Lewis rat renal CAN model was established via a modified Kamada procedure. The recipients were first treated with CsA, 10 mg/kg/d, for 10 days and then allocated randomly to three oral treatment groups: control; CsA, 6 mg/kg/d; and rapamycin, 0.8 mg/kg/d. At 4, 8, and 12 weeks posttransplantation, the rats were killed to harvest the renal allografts. The serum creatinine concentration (SCr) was measured, and the pathologic changes were assessed according to Banff 97 criteria. The expression of messengerRNA and proteins of Ang1, Ang2, and Tie2 was determined using real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry. The elevation of SCr and the pathologic changes of CAN were observed in the control and CsA groups at 8 and 12 weeks; the differences between the 2 groups were not significant (P > .05). The levels of SCr and Banff score in the rampamycin group were lower than those in other 2 groups (P < .01). The expression of Ang1 and Ang2 was localized to epithelial cells and endothelium of vascular bundles of glomeruli, and Tie2 was specifically expressed in the endothelium of vessels in all 3 groups. At 4 weeks, the differences in mRNA expression of Ang1, Ang2, and Tie2 between 3 groups were not significant (P > .05). In a comparison of the control and CsA groups, mRNA expression of Ang1 was increased (P < .05), and mRNA expression of Ang2 and Tie2 was decreased (P < .05) in the rapamycin group at 8 and 12 weeks. The differences between the control and CsA groups were not significant at 8 or 12 weeks (P > .05). Our results show that compared with CsA, rapamycin modulates the expression of Ang1, Ang2, and Tie2 in rat renal allografts with CAN, which suggests that rapamycin may improve the long-term survival of renal allografts through its vasculoprotective properties.


Resurgence of methamphetamine related burns and injuries: a follow-up study.
Legislation enacted to curb methamphetamine production has only temporarily succeeded. Experiencing a recent increase in burns as a result of the new one-pot method, we compared methamphetamine related burn patients who utilized the previous anhydrous ammonia method of production to current patients who largely used the new one-pot method of production. Patients who were burned as a result of methamphetamine production were retrospectively reviewed. Comparisons were made including demographics, length of stay, injury severity score, hospital charges, total body surface area burned, inhalation injury, intubation, ventilator days, toxicology, fluid volumes, surgeries and complications. Eighteen current study patients (88.9% male) were compared to twenty-nine (86.2% male) previous study patients. The groups were similar in age, pattern of burn injury and intubation. Total body surface area burned, injury severity score, inhalation injuries, and ventilator days were not significantly increased in the current study. Longer length of stay and greater hospital charges were incurred by the current group. Burn surgeries per patient were significantly increased in the current group. A new one-pot method has emerged despite legislative attempts to curtail methamphetamine production, and burns have also increased. The reason for more extensive burn surgeries in the current METH related burn patients remains enigmatic. Severity of injury and cost to society remain high.


Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist.
Pegvisomant is a GH receptor antagonist that blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin (SMS) analogs, does not suppress the activity of the GH-producing adenoma. We assessed the effects of cotreatment with pegvisomant and SMS in acromegaly on GH secretion, IGF-I levels, and glucose tolerance. Eleven patients with persistent disease despite previous therapy underwent the following fixed treatment algorithm: 1) on SMS therapy, 2) off therapy for 2 months, 3) 6-wk treatment with 10 mg/d pegvisomant, 4) 6-wk treatment with 15 mg/d pegvisomant, and 5) 3-month treatment with 15 mg pegvisomant plus SMS. Blood was sampled in the fasting state and during an oral glucose tolerance test. Total serum IGF-I levels (micrograms per liter) decreased after pegvisomant, but the lowest levels were obtained with cotreatment [458 +/- 67 (SMS), 562 +/- 78 (active), 376 +/- 51 (10 mg), 269 (15 mg), 195 +/- 24 (combined) (P < 0.0001)]. Free and bioactive IGF-I changed in a similar pattern. Steady-state pegvisomant levels (micrograms per liter) were obtained, but SMS cotreatment increased pegvisomant levels by 20% (P = 0.02) [2631 +/- 616 (10 mg), 6536 +/- 1413 (15 mg), 8030 +/- 1914 (combined)]. Pegvisomant increased endogenous GH levels (micrograms per liter), which was countered by SMS cotreatment [5.1 +/- 1.3 (SMS), 8.9 +/- 2.9 (active), 14.6 +/- 4.9 (10 mg), 19.7 +/- 6.5 (15 mg), 11.8 +/- 2.8 (combined) (P < 0.01)]. Plasma glucose levels (millimoles per liter) were highest during SMS and lowest during pegvisomant 15 mg [2-h oral glucose tolerance test: 10.3 +/- 0.7 (SMS), 8.9 +/- 0.7 (active), 7.2 +/- 0.7 (10 mg), 6.5 +/- 0.5 (15 mg), 8.0 +/- 0.8 (combined) (P = 0.02)]. Dual blockade of the GH axis with pegvisomant and a SMS analog is feasible in acromegaly.


In vitro maturation and fertilization of porcine oocytes after a 48 h culture in roscovitine, an inhibitor of p34cdc2/cyclin B kinase.
Maintaining oocytes at the germinal vesicle (GV) stage in vitro may permit enhanced acquisition of the developmental competence. The objective of the current study was to evaluate the nuclear and cytoplasmic maturation in vitro of porcine oocytes after pretreatment with S-roscovitine (ROS). Cumulus oocyte complexes (COC) were treated with 50 microM ROS for 48 h and then matured for various lengths of time in a conventional step-wise in vitro maturation (IVM) system by using dibutyryl cyclic AMP. The COC that were matured in the same system for 44 h without pretreatment with ROS were used as the control group. At various periods after the start of IVM, oocytes were assessed for the meiotic stages and subjected to in vitro fertilization (IVF) with fresh spermatozoa. The ROS treatment inhibited GV breakdown of 94.4% oocytes, with the majority arrested at the GV-I stage (67.4%). Maximum maturation rate to the metaphase-II stage after ROS treatment was achieved by 44 h of IVM (92.1%) and no differences were observed with control oocytes (95.0%). Penetration rate was correlated to the maturation rate. The duration of IVM had no effects on polyspermy and male pronuclear (MPN) formation rates at 8 h post insemination (hpi), whereas both rates increased at 22 hpi. Direct comparison with controls assessed at 22 hpi confirmed a lesser MPN formation in ROS-treated oocytes (73.7% compared with 53.6%). Glutathione (GSH) concentrations were less in oocytes treated with ROS than in control oocytes (5 compared with 7.7 pmol/oocyte) as well as blastocyst rate (22.0% compared with 38.1%, respectively). These results demonstrate that cytoplasmic maturation in porcine oocytes pretreated with ROS for 48 h did not equal that of control oocytes in the current IVM system.


Development of a marker panel for genotyping of domestic soybean cultivars for genes controlling the duration of vegetation and response to photoperiod.
Soybean, Glycine max L., is one of the most important agricultural crops grown in a wide range of latitude. In this regard, in soybean breeding, it is necessary to pay attention to the set of genes that control the transition to the f lowering stage, which will make it possible to adapt genotypes to local growing conditions as accurately as possible. The possibilities of soybean breeding for this trait have now signif icantly expanded due to identif ication of the main genes (E1-E4, GmFT2a, GmFT5a) that control the processes of f lowering and maturation in soybean, depending on the day length. The aim of this work was to develop a panel of markers for these genes, which could be used for a rapid and eff icient genotyping of domestic soybean cultivars and selection of plant material based on sensitivity to photoperiod and the duration of vegetation. Combinations of 10 primers, both previously developed and our own, were tested to identify different alleles of the E1-E4, GmFT2a, and GmFT5a genes using 10 soybean cultivars from different maturity groups. As a result, 5 combinations of dominant and recessive alleles for the E1-E4 genes were identif ied: (1) e1-nl(e1-as)/ e2-ns/e3-tr(e3-fs)/e4; (2) e1-as/e2-ns/e3-tr/E4; (3) e1-as/e2-ns/E3-Ha/e4; (4) E1/e2-ns/e3-tr/E4; (5) e1-nl/e2-ns/E3-Ha/E4. The studied cultivars contained the most common alleles of the GmFT2a and GmFT5a genes, with the exception of the 'Cassidi' cultivar having a rare dominant allele GmFT5a-H4. The degree of earliness of cultivars positively correlated with the number of recessive genes E1-E4, which is consistent with the data of foreign authors on different sets of cultivars from Japan and North China. Thus, the developed panel of markers can be successfully used in the selection of soybean for earliness and sensitivity to photoperiod.


Measurements of occupational exposure to switched gradient and spatially-varying magnetic fields in areas adjacent to 1.5 T clinical MRI systems.
To determine if magnetic field exposure close to two clinical 1.5 T magnetic resonance imaging (MRI) scanners during image acquisition and when moving in the spatially-varying static magnetic field is compliant with European Union (EU) Directive 2004/40/EC (the Directive). Using commercially available equipment we measured the magnetic flux density around the scanners during two clinical pulse sequences. The data was compared with frequency-dependent limits that will limit occupational exposure following transposition of the Directive into national law in 2008. The static magnetic field was measured around the scanners and the exposure from movement within this field was simulated. The whole-body exposure experienced when standing close to the face of the magnet exceeds the limits in the Directive on the two scanners tested during clinical sequences. Simulation of movement toward the scanner shows that speeds must be restricted to 1/5 of normal walking speed to comply with the Directive. EU Directive 2004/40/EC will have a major impact on the current use and future development of MRI due to limitations on exposure to time-varying gradient fields and movement within the spatially-varying static field. This will make interventional work impossible and routine MRI use impracticable in Europe.


Right Atrial Phasic Function in Heart Failure with Preserved Ejection Fraction: Cardiac Magnetic Resonance Feature Tracking and Outcomes.
This study sought to investigate the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) and atrial fibrillation (AF). Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR, feature tracking of the RA wall was performed during CMR. In addition, all patients underwent right and left heart catheterization and 6 min walk distance (6MWD) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluations. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70 ± 8 years old) were included. Ninety-two patients (49%) were in persistent AF. Eighty-five patients reached the combined endpoint during a follow-up of 69 (42-97) months. After a multivariate cox regression analysis, the impaired RA reservoir strain (HR 0.949; 95% CI [0.909-0.990], p = 0.016), the RA reservoir strain rate (HR 0.991; 95% CI [0.983-0.999], p = 0.028), the RA conduit strain (HR 0.932; 95% CI [0.879-0.988], p = 0.019), and the RA conduit strain rate (HR 0.989; 95% CI [0.881-0.997], p = 0.011) were significantly associated with a worse outcome for patients in SR. In persistent AF, no RA imaging parameter was related to outcome after a multivariate regression analysis. In HFpEF patients in SR, CMR parameters of impaired RA conduit and reservoir function are associated with dismal cardiovascular outcomes. In persistent AF, RA parameters lose their prognostic ability.


Evaluation of a novel rapid diagnostic test for Schistosoma haematobium based on the detection of human immunoglobulins bound to filtered Schistosoma haematobium eggs.
To determine whether the detection of human IgG bound to Schistosoma haematobium eggs from filtered urine could be used as a rapid diagnostic test (RDT-Sh). We filtered 160 urine samples from children in the Kwale District of Kenya to isolate S. haematobium eggs and used anti-human IgG antibody conjugated to horseradish peroxidase to bind to the human IgG attached to the eggs. We then added 3,3'5,5'-tetramethylbenzidine base (TMB), which turns blue in the presence of horseradish peroxidase to detect the S. haematobium eggs. The RDT-Sh was compared in a blinded manner to urine microscopy. The RDT-Sh was positive in 89% of urine samples containing >1 egg/10 ml (58/65 samples) and 97% of urine samples containing >11 eggs/10 ml urine (35/36 samples) seen by microscopy. The RDT-Sh was negative 79% of the time when no eggs were seen on urine microscopy, but because up to three times more urine was used for the RDT-Sh, there were likely cases in which eggs were on the RDT-Sh filter but not detected by microscopy. We used latent class analysis incorporating urine microscopy, haematuria, proteinuria and RDT-Sh results to determine an overall 97% sensitivity and 78% specificity for RDT-Sh, 96% and 81% for urine microscopy, 71% and 98% for microscopic haematuria and 46% and 89% for proteinuria, respectively. The RDT-Sh is quick, inexpensive and easy to perform in the field for the diagnosis of S. haematobium.


Morphometric aspects of reflux nephropathy.
We have studied the relationships between renal size, glomerular hypertrophy and sclerosis and renal function in adults with reflux nephropathy. A digitizer was used to measure the renal surface areas in intravenous pyelogram films. This was then corrected for patient size by dividing by the area of the first three lumbar vertebrae. In renal biopsies, glomerular surface area and the proportion of segmentally and globally sclerosed glomeruli were measured and compared with a control group of 17 renal donors. Of 57 patients studied, 45 had intravenous pyelogram films and 32 had renal biopsy tissue available from the time of presentation, 20 had both. Thirty-one were followed for two years or more (median 6 years, range 2 to 11 years). There were positive correlations between corrected renal size and renal function, and inverse correlations between these and maximum glomerular size, the proportion of sclerosed glomeruli and vascular wall thickness. Proteinuria correlated best with the proportion of segmentally sclerosed glomeruli. As a prognostic guide, the strongest correlations were between rate of functional decline and percent segmental sclerosis, urine protein excretion and creatinine clearance at presentation. These studies confirm expected relationships between renal size, glomerular size and renal function and suggest that the severity of segmental sclerosis is a major factor in eventual decline into renal failure.


Asymmetric Wacker-Type Oxyallenylation and Azaallenylation of Cyclic Alkenes.
Palladium-catalyzed three-component carboetherification of cyclic alkenes proceeded to give trans adducts exclusively with excellent enantioselectivity through a Wacker-type pathway. The reaction is also applicable to other oxygen nucleophiles, such as water, phenols, and carboxylic acids, as well as some electron-poor aryl amines.


Introduction of wild-type patched gene suppresses the oncogenic potential of human squamous cell carcinoma cell lines including A431.
Defects in a developmental signaling pathway involving the mammalian homologue of the Drosophila segment polarity gene, patched are associated with human tumors such as basal cell carcinoma, medulloblastoma and squamous cell carcinoma. Loss of heterozygosity (LOH) in some of these tumor cells suggests that patched functions as a tumor suppressor gene. To evaluate the biological significance of patched mutations in human sporadic tumor cells, we constructed a VSV-G pseudotyped retrovirus vector carrying the wild-type patched gene and transduced it into two human squamous cell carcinoma (SCC) cell lines, A431 and KA, that express only mutant patched mRNA. When SSC cells were transduced with Ptc virus, colony forming activity in soft agar was drastically reduced and these cells recovered anchorage independent growth when Sonic hedgehog (Shh), the ligand of Patched (Ptc), was added into the soft agar culture. Expression of exogenous patched, however, had no effect on anchorage independent growth of Ras-transformed NIH3T3 cells or SCC cell line, NA, which expresses wild-type patched mRNA. Cyclopamine, a specific inhibitor of the Shh/Ptc/Smo signaling pathway, efficiently suppressed anchorage independent growth of A431 and KA cells. These results indicate that loss of patched function plays a major role in the acquisition of oncogenic potential in these SCCs and further that Ptc virus would be an effective reagent for suppressing tumorigenicity of such SCCs.


Cerebral venous sinus thrombosis as an initial manifestation of primary antiphospholipid syndrome.
Cerebral venous sinus thrombosis is a rare neurologic manifestation of antiphospholipid syndrome. We report a case of a 49-year-old woman who presented to the emergency department with recurrent episodes of transient clumsiness of the left upper extremity. The results of unenhanced brain computed tomography and electroencephalography were unremarkable. Serial neuroimages revealed superior sagittal sinus thrombosis. Thrombophilia screen disclosed positive lupus anticoagulant. In this case report, we aim to emphasize the significance of recognizing an unusual presentation of antiphospholipid syndrome.


The use of dentinal etching with endodontic bleaching procedures.
The removal of the smear layer from dentinal surfaces has been shown to increase significantly the permeability of dentin in both vital and endodontically treated teeth by opening the orifices of the dentinal tubules. This knowledge has led to the practice of acid etching the intracoronal dentin of endodontically treated teeth prior to nonvital bleaching procedures in order to increase the speed and effectiveness of the bleach. In this study extracted human teeth, which had been stained in vitro, were used to compare the effects of dentinal etching of the pulp chambers with no acid etching in conjunction with "walking bleach" procedures. In one experimental group, the pulp chambers were acid etched with 50% phosphoric acid for 1 min to remove the smear layer prior to insertion of the 30% hydrogen peroxide/sodium perborate bleaching agents. The second group had the same chamber preparation except the acid etching was deleted. Evaluators were unable to distinguish a significant difference between the effectiveness of the bleaching procedures in the two experimental groups.


Metal effects on phenol oxidase activities of soils.
This study evaluates the effects of various metals, in concentrations ranging from 0 to 800 mM, on the phenol oxidase (PO) activities of three Mediterranean soils. Dose-response curves (DRC) were established for each metal and were divided into four groups according to metal effects on PO activity: inhibition, stimulation followed by inhibition, stimulation, and no effect. The area under dose-response curves (AUDRC) allowed metal effects on PO activities to be ranked. Results of statistical analyses of variance show that metals had more pronounced effects than soil or metal salt form (i.e., chloride or sulfate) on PO activities. Hence, according to the mean values of the AUDRC for each metal tested, PO activities were preferentially stimulated by Mg(II), Mn(II), Zn(II) and were inhibited in order by Cd(II)<Ni(II)<Cu(II)<Pb(II)<Al(III)<Co(II)<Ba(II)<Sn(II)<Fe(II).


Safe exposure of the left renal vein during laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: anatomical variations and pitfalls.
The left renal vein is technically difficult to expose during laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma despite being an important landmark for posterior dissection. We hereby propose a novel technique to safely expose the left renal vein while avoiding the associated anatomical pitfalls. The anatomy of the left renal artery and vein was analyzed using multidetector computed tomography. We initially exposed the left renal vein on the left posterior side of the superior mesenteric artery followed by exposure toward the left kidney. We retrospectively examined the perioperative results of this technique in 33 patients who underwent laparoscopic distal pancreatectomy. 15.7% of the patients had an accessory left renal artery coursing cranial to the vein. In 43.1%, the left renal arterial branch ventrally traversed the vein at the renal hilum, thereby posing a risk for arterial injury. The location of the left renal vein varies cranial (17.6%) or caudal (82.4%) to the pancreas. The left renal vein was exposed without any vascular injury using this technique. The median operative time was 259 min, blood loss was 18 mL, and R0 resection rate was 97.0%. The initial exposure of the left renal vein should, therefore, be on the left posterior side of the superior mesenteric artery.


Generation of 2,3,7,8-TCDD-metabolizing enzyme by modifying rat CYP1A1 through site-directed mutagenesis.
Polychlorinated dibenzo-p-dioxins (PCDDs) are known as g environmental contaminants on account of the extreme toxicity. Among these compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TetraCDD) is regarded as the most toxic one. The extremely high toxicity of 2,3,7,8-TetraCDD is based on its high affinity for Ah receptor and nearly undetectable metabolism in mammalian body. Based on our previous studies, we assumed that enlarging the space of substrate-binding pocket of rat CYP1A1 might generate the catalytic activity toward 2,3,7,8-TetraCDD. Large-sized amino acid residues located at putative substrate-binding sites of rat CYP1A1 were substituted for alanine by site-directed mutagenesis. Among eight mutants examined, the mutant in the putative F-G loop, F240A, showed metabolic activity toward 2,3,7,8-TetraCDD. HPLC and GC-MS analyses strongly suggested that the metabolite was 8-hydroxy-2,3,7-TriCDD. Ah receptor assay revealed that the affinity of 8-hydroxy-2,3,7-TriCDD for Ah receptor was less than 0.01% of 2,3,7,8-TetraCDD, indicating that the F240A-dependent metabolism resulted in remarkable detoxification of 2,3,7,8-TetraCDD. The novel 2,3,7,8-TetraCDD-metabolizing enzyme could be applicable to bioremediation of contaminated soils with dioxin, elimination of dioxin from foods, and clinical treatment for people who accidentally take dioxin into their systems.


Factors affecting knowledge of sexually transmitted infection transmissibility in healthcare providers: results from a national survey.
The objectives of this study were to examine healthcare providers' knowledge of the transmissibility of sexually transmitted infections (STIs) and identify knowledge determinants. Questionnaires were completed March through May 2004 by a representative sample of Canadian healthcare providers, yielding a corrected response rate of 50.8% for physicians. STI workers returned 236 questionnaires. For physicians, the distribution of HIV estimates was positively skewed (mode = 10%), whereas chlamydia estimates were widely dispersed. STI workers showed a trimodal (0%, 50%, and 100%) distribution of HIV estimates and a negatively skewed distribution of chlamydia estimates (mode = 100%). Overall, 1.4% (HIV) and 5.8% (chlamydia) of respondents gave estimates close to the actual transmission probabilities. More years of medical experience and higher estimates of STI prevalence predicted higher transmissibility estimates (95% confidence intervals). That only a small percentage of healthcare providers are aware of the actual transmissibility of HIV and chlamydia has implications for improving medical and sexual health training.


Sonochemically fabricated microelectrode arrays for biosensors. Part III. AC impedimetric study of aerobic and anaerobic response of alcohol oxidase within polyaniline.
A sonochemically fabricated alcohol oxidase enzyme micro-electrode array is reported. Sensors of this type were fabricated by first depositing an insulating polydiaminobenzene film on supporting gold electrodes. Sonication and subsequent ablation exposed discrete areas of the underlying conducting electrode, which collectively act as a microelectrode array. Electropolymerisation of aniline has been used to generate in situ polyaniline containing entrapped alcohol oxidase. The physical and electrochemical properties of these films were studied and reported within this paper. The final composites were shown to behave with microelectrode performance characteristics for the detection of aqueous ethanol concentrations.


PTN-PTPRZ1 signaling axis blocking mediates tumor microenvironment remodeling for enhanced glioblastoma treatment.
Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis that is highly heterogeneous and invasive. One of the most major challenges of GBM treatment in the clinic is the blood-brain barrier (BBB). Additionally, the tumor microenvironment (TME) is highly enriched with immunosuppressed M2-like tumor-associated macrophages (M2 TAMs) and glioblastoma stem cells (GSCs), which promoted the malignancy of GBM through the PTN-PTPRZ1 signaling axis. Here, we developed a self-assembled dual-targeted hybrid micelle (DT-GM1) as a nanocarrier to deliver the chemotherapeutic agent doxorubicin (DOX). We demonstrated that this DT-GM1/DOX can cross the BBB using in vitro and in vivo GBM models, and that M2pep and PTPRZ1 antibodies allow it to precisely target the tumor microenvironment where M2 TAMs and GSCs are enriched, increasing intracellular drug accumulation via multiple internalization pathways. Additionally, simultaneous elimination of M2 TAMs and GSCs blocked the PTN-PTPRZ1 signaling axis, resulting in less M2 TAM infiltration and increased polarization to the M1 phenotype, reshaping the immune microenvironment. Overall, we have established a nanocarrier that can penetrate the BBB and target the TME while also synergizing with GBM chemotherapeutic agents, providing a promising new strategy for GBM treatment.