Cholangiocellular carcinoma of the liver.
Of the 118 patients with primary liver cancer treated in our clinic during a 6 year 7 month period, 11 patients had cholangiocellular carcinoma of the liver. Ten (90.9 percent) of the 11 patients underwent surgery, and 9 (90 percent) had major hepatic resection with no operative deaths. Seven were still alive at the time of the study 2 months to 4 years 1 month after surgery. Three patients died from recurrence 9 months, 11 months, and 1 year 4 months after surgery. The 1 and 3 year actuarial survival rates after hepatic resection were excellent (85.7 and 61.2 percent, respectively) compared with the 1 and 3 year rates of 58.8 and 0 percent in the Japanese series. Even though the cholangiocellular carcinomas in our 11 patients were in the advanced stages, good results were obtained by hepatic resection. If they were detected at a much earlier time, an even more remarkable survival rate could be expected.


Effects of photobiomodulation therapy (PBMT) on bovine sperm function.
Fertilization rates and subsequent embryo development rely on sperm factors related to semen quality and viability. Photobiomodulation therapy (PBMT) is based on emission of electromagnetic waves of a laser optical system that interact with cells and tissues resulting in biological effects. This interaction is mediated by photoacceptors that absorb the electromagnetic energy. Effects are dependent of irradiation parameters, target cell type, and species. In sperm, PBMT improves several features like motility and viability, affecting sperm aerobic metabolism and energy production. The aim of this study was to investigate, under same conditions, how different output powers (5, 7.5, and 10 mW) and time of irradiation (5 and 10 min) of laser (He-Ne laser, 633 nm) may affect frozen/thawed bovine sperm functions. Results showed significant effects depending on power while using 10 min of irradiation on motility parameters and mitochondrial potential. However, no effect was observed using 5 min of irradiation, regardless of power applied. In conclusion, PBMT is effective to modulate bovine sperm function. The effectiveness is dependent on the interaction between power applied and duration of irradiation, showing that these two parameters simultaneously influence sperm function. In this context, when using the same fluency and energy with different combinations of power and time of exposure, we observed distinct effects, revealing that biological effects should be also based on simple parameters rather than only composite parameters such as fluency, irradiance and energy. Laser irradiation of frozen/thawed bovine semen led to an increase on mitochondrial function and motility parameters that could potentially improve fertility rates.


Predicted topology of the N-terminal domain of the hydrophilic subunit of the mannose transporter of Escherichia coli.
A folding topology for the homodimeric N-terminal domain (IIA, 2 x 14 kDa) of the hydrophilic subunit (IIABman) of the mannose transporter of E. coli is proposed. The prediction is based on (i) tertiary structure prediction methods, and (ii) functional properties of site-directed mutants in correlation with NMR-derived alpha/beta secondary structure data. The 3D structure profile suggested that the overall fold of IIA is similar to that of the unrelated protein, flavodoxin, which is an open-stranded parallel beta-sheet with a strand order of 5 4 3 1 2. The 3D model of IIA, constructed using the known atomic structure of flavodoxin, is consistent with the results from site-directed mutagenesis. Recently NMR results confirmed the open parallel beta-sheet with a strand order of 4 3 1 2 (residues 1-120) of our model whereas beta-strand 5 (residues 127-130) was shown to be antiparallel to beta-strand 4. The correctly predicted fold includes 90% of the monomeric subunit sequence and contains all functional sites of the IIA domain.


Peroxisomes: identification in freeze-etch preparations of rat kidney.
The definitive identification of peroxisomes in freeze-etch preparations of normal mammalian cells has been impeded due to their similarity to other globular cytoplasmic organelles, especially the lysosomes. In the proximal tubules of the rat kidney there is a distinct group of large microbodies with an angular shape and crystalline inclusions which have now been identified in freeze-etch replicas. Rat kidneys were fixed by perfusion with glutaradehyde and processed for catalase cytochemistry and freeze-etching. In ultrathin sections catalase positive peroxisomes 0.5-2 microns in diameter with an angular multifaceted shape and scalloped margins were found. In freeze-etch replicas particles with the same size, shape, and intracellular distribution were found; these contained branching and anastomosing tubular inclusions. The tubules, 100-125 nm in diameter, left deep impressions upon the limiting membrane of peroxisomes. A crystalline pattern with a periodicity of approximately 92 +/- 8 A perpendicular to the axis of the tubles was noted on the E-face of the microbody membrane. In addition, a few membrane particles were present on the E-face, but many more particles were noted on the P-face of the microbody membrane. The cisternae of ER, with typical fenestrations, wrapped around large portions of the surface of peroxisomes, thus demonstrating the close association of these two organelles.


Selective early elimination of luteal support in assisted reproduction cycles using a gonadotropin-releasing hormone agonist during ovarian stimulation.
To determine if women undergoing GnRH agonist-hMG stimulated IVF cycles can undergo successful discontinuation of luteal phase support. A protocol for selective discontinuation of luteal phase support was evaluated prospectively in women undergoing assisted reproduction cycles. A tertiary care institutional-based assisted reproduction program. One hundred eighty-eight women who conceived after an IVF or zygote intrafallopian transfer cycle including a GnRH agonist between January 1994 and June 1997. Women with serum progesterone levels of > or = 60 ng/mL at 4 weeks' gestation were selected for discontinuation of their luteal phase support. Delivery rate. Sixty-three women (62.4%) met the criteria for discontinuation of luteal phase support. There were no differences in the mean age, peak E2 levels, number of follicles, number of embryos transferred, or delivery rates (85.7% versus 78.9%) between the women who did and those who did not have discontinuation of their progesterone supplementation. These data reveal that luteal phase support can be discontinued successfully for selective women undergoing IVF who are receiving a GnRH agonist.


Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus.
We previously observed that ivermectin-induced detoxification genes, including ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) were identified from body lice following a brief exposure to a sublethal dose of ivermectin using a non-invasive induction assay. In this current study, the functional properties of PhABCC4 and CYP6CJ1 were investigated after expression in either X. laevis oocytes or using a baculovirus expression system, respectively. Efflux of [3 H]-9-(2-phosphonomethoxyethyl) adenine ([3 H]-PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA-injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors. Efflux was also determined to be ATP-dependent. Using a variety of insecticides in a competition assay, only co-injection of ivermectin and dichlorodiphenyltrichloroethane led to decreased efflux of [3 H]-PMEA. PhABCC4-expressing oocytes also directly effluxed [3 H]-ivermectin, which increased over time. In addition, ivermectin appeared to be oxidatively metabolized and/or sequestered, although at low levels, following functional expression of CYP6CJ1 along with cytochrome P450 reductase in Sf9 cells. Our study suggests that PhABCC4 and perhaps CYP6CJ1 are involved in the Phase III and Phase I xenobiotic metabolism of ivermectin, respectively, and may play an important role in the evolution of ivermectin resistance in lice and other insects as field selection occurs.


Bis(mandelato)borate: an effective, inexpensive spiroborate anion for chiral resolution.
Bis(mandelato)borate [B(Man)2](-) (R- or S-) anions are simply prepared and appear widely effective for resolution of racemic cations. Three examples demonstrate their scope; the alkaloid tetrahydropalmatine (THP), 1,2-diaminopropane (1,2-dap) and the metal-organic complex [Co(phen)3](3+) are readily resolved, either by a facile one-pot procedure, or via counter-ion metathesis.


Occupancy of aldosterone binding sites in rat kidney cytosol.
The binding sites for aldosterone and a potent aldosterone antagonist (SC-26304) were studied in kidney cytosol from adrenalectomized rats. Preformed cytosol and kidney slices were incubated with 3H-labeled steroids in a wide range of concentrations. The recovery and characteristics of the binding sites were affected by the incubation and homogenization conditions. High-affinity, Type I mineralocorticoid binding was reduced by more than 95% when cytosol was incubated at 25 degrees C in the presence of calcium. Tissue dilution also affected the binding sites. SC-26304 was bound to high- and low-affinity receptors, similar to the binding of aldosterone. The physiologic response to aldosterone could result from binding to either or both sets of sites. Some of the physiologic responses to spirolactones could represent antagonism of the binding of aldosterone to either or both sites. A convenient method is presented for describing the relative occupancy of several different sites by any particular steroid.


Nanopreparations to overcome multidrug resistance in cancer.
Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing microtumor tissues in vitro are discussed in detail.


Nonverbal Emotions While Disclosing Child Abuse: The Role of Interviewer Support.
Statements by alleged victims are important when child abuse is prosecuted; triers-of-fact often attend to nonverbal emotional expressions when evaluating those statements. This study examined the associations among interviewer supportiveness, children's nonverbal emotions, and informativeness during 100 forensic interviews with alleged victims of child abuse. Raters coded the silent videotapes for children's nonverbal emotional expressions while other raters coded the transcripts for interviewer support, children's verbal emotions, and informativeness. Results showed that children's nonverbal signals were more common than and preceded the verbal signs. Interviewer support was associated with children's expressivity. When children expressed more nonverbal emotions, they were more responsive during the pre-substantive phases and more informative about the abuse. Nonverbal emotions partially mediated the association between support and informativeness. The findings underline the value of nonverbal emotional expression during forensic interviews and demonstrate how the interviewers' supportive demeanor can facilitate children's emotional displays and increase informativeness.


An experimental evaluation of tic suppression and the tic rebound effect.
Tourette's syndrome (TS) is a neurobiological disorder consisting of motor and vocal tics that are thought to be temporarily suppressible. Many professionals, however, believe that a paradoxical increase in tic frequency (above baseline levels) occurs when efforts to suppress have ceased (i.e., a rebound effect). To date, little research has investigated tic suppression or its effects. This study examined tic frequency during baseline, suppression, and post-suppression conditions using an experimental preparation reported to reliably produce tic suppression in children. Six children with TS and one with chronic tic disorder (CTD) were recorded during baseline and repeated suppression and post-suppression conditions. Tic frequency was significantly lower during suppression as compared to baseline. Although tic frequency during post-suppression was higher than during suppression, it was lower than baseline levels, arguing against a "rebound" effect of tic suppression. Exploratory analyses revealed that scores on the attention problems subscale of the Child Behavior Checklist significantly predicted tic suppressibility. The relationships between age, tic severity, and tic suppressibility were also explored.


The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells.
The two distinct members of the mitogen-activated protein (MAP) kinase family c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, play an important role in central nervous system (CNS) development and differentiation. However, their role and functions are not completely understood in CNS. To facilitate in vitro study, we have established an immortal stem cell line using SV40 from fetal rat embryonic day 17. In these cells, MAP kinase inhibitors (SP600125, SB202190, and PD98059) were treated for 1, 24, 48, and 72 h to examine the roles of protein kinases. Early inhibition of JNK did not alter phenotypic or morphological changes of immortalized cells, however overexpression of Bax and decrease of phosphorylated AKT was observed. The prolonged inhibition of JNK induced polyploidization of immortalized cells, and resulted in differentiation and inhibition of cell proliferation. Moreover, JNK and p38 MAP kinase but not ERK1/2 was activated, and p21, p53, and Bax were overexpressed by prolonged inhibition of JNK. These results indicate that JNK and p38 MAP kinase could play dual roles on cell survival and apoptosis. Furthermore, this established cell line could facilitate study of the role of JNK and p38 MAP kinase on CNS development or differentiation/apoptosis.


Meniscal injuries associated with rupture of the anterior cruciate ligament: a retrospective study.
The purpose of this study was to demonstrate the extent of meniscal involvement when the anterior cruciate ligament is torn. Data from 189 cases operated on for lesions of the anterior cruciate ligament form the basis of this report. The patients chosen for this study were all athletes forming two main groups. In one group, 82 patients were operated on immediately after their initial injury and in the other group 107 patients came for treatment because of persistent symptoms. It was recorded in the case notes whether there were any articular cartilage changes found at operation. Meniscal involvement was noted in 24.4 per cent of the patients of the first group. In particular, the meniscus was found to be torn in 20.6 per cent of the so-called 'isolated' tears and in 27.1 per cent of the combined cruciate injuries. No articular cartilage changes were noted in this group. In the second group meniscal injuries were seen in 61.6 per cent of the cases. More specifically, the menisci were involved in 26.7 per cent of the knees with first-degree instability, in 57.5 per cent with second-degree, rising to 75 per cent in knees with third-degree instability. Articular cartilage changes were seen in 20 per cent, 67.5 per cent and 78.8 per cent respectively. There is ample evidence in our study of the progressive meniscal involvement and degeneration in the knee of the athletically active individual after an anterior cruciate ligament rupture.


Induction of outward current by orexin-B in mouse peritoneal macrophages.
To define effects of novel feeding regulating peptides, orexins, in immunocompetent cells, ion channel activity in mouse peritoneal macrophages was analyzed by the perforated patch-clamp method. Orexin-B (OX-B) induced an outward current at smaller holding potentials than K+ equilibrium potentials. Reversal potentials of OX-B induced current were dependent on external K+ concentrations but not on external Cl- concentration. Orexin-A is less effective than OX-B. Quinine blocked the outward current and tetraethylammonium partially suppressed the current. These results suggest that OX-B can modulate macrophage functions through the activation of Ca2+-dependent K2+ channels.


Research and guidelines for implementing Fatigue Risk Management Systems for the French regional airlines.
This paper describes research that aims to provide the overall scientific basis for implementation of a Fatigue Risk Management System (FRMS) for French regional airlines. The current research has evaluated the use of different tools and indicators that would be relevant candidates for integration into the FRMS. For the Fatigue Risk Management component, results show that biomathematical models of fatigue are useful tools to help an airline to prevent fatigue related to roster design and for the management of aircrew planning. The Fatigue Safety assurance includes two monitoring processes that have been evaluated during this research: systematic monitoring and focused monitoring. Systematic monitoring consists of the analysis of existing safety indicators such as Air Safety Reports (ASR) and Flight Data Monitoring (FDM). Results show a significant relationship between the hours of work and the frequency of ASR. Results for the FDM analysis show that some events are significantly related to the fatigue risk associated with the hours of works. Focused monitoring includes a website survey and specific in-flight observations and data collection. Sleep and fatigue measurements have been collected from 115 aircrews over 12-day periods (including rest periods). Before morning duties, results show a significant sleep reduction of up to 40% of the aircrews' usual sleep needs leading to a clear increase of fatigue during flights. From these results, specific guidelines are developed to help the airlines to implement the FRMS and for the airworthiness to oversight the implementation of the FRMS process.


The role of cardiac rehabilitation in patients with heart disease.
Cardiac rehabilitation is a valuable treatment for patients with a broad spectrum of cardiac disease. Current guidelines support its use in patients after acute coronary syndrome, coronary artery bypass grafting, coronary stent placement, valve surgery, and stable chronic systolic heart failure. Its use in these conditions is supported by a robust body of research demonstrating improved clinical outcomes. Despite this evidence, cardiac rehabilitation referral and attendance remains low and interventions to increase its use need to be developed.


BRIEF REPORT: Factors affecting outpatient follow-up compliance of emergency department patients.
Emergency department (ED) patients often fail to follow-up with referrals to outpatient clinics and physicians. To compare the effects of 2 ED discharge instructional methods on outpatient follow-up compliance and to evaluate sociodemographic characteristics as possible factors affecting outpatient follow-up compliance. Randomized trial of ED patients. At discharge, the intervention group had their follow-up appointment made and the standard group was given our hospital's referral service phone number to make their own follow-up appointment. Outpatient clinics were called 1 month after each subject's ED discharge to ascertain if they followed-up. Poisson regression was used to examine the effects of sociodemographic factors on follow-up compliance. Of 287 eligible subjects, 250 (87%) agreed to participate. Follow-up rates were 59% for the intervention group and 37% for the standard group (P<.001). Having a primary care physicians appeared to increase ED patients' outpatient follow-up compliance and having Medicaid insurance appeared to decrease outpatient follow-up compliance, but neither of these findings was statistically significant. In our ED, patients who have their outpatient follow-up appointment made at discharge have a significantly greater probability of follow-up compliance compared with patients given standard discharge instructions. Most sociodemographic characteristics do not affect our ED patients' follow-up compliance.


Epidemiology and socio-economic aspects of osteoporosis in Finland.
The public health problem of osteoporosis is assessed epidemiologically and economically. Osteoporosis is mainly a problem of old people. Ageing of the population will increase the number of osteoporotic fracture patients and the need of hospital and other services. It is possible to prevent osteoporosis and the goal of health planning activities should thus be directed more to the prevention of osteoporosis.


A Perspective on Cell Therapy and Cancer Vaccine in Biliary Tract Cancers (BTCs).
Biliary tract cancer (BTC) is a rare, but aggressive, disease that comprises of gallbladder carcinoma, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with heterogeneous molecular profiles. Advanced disease has limited therapeutic options beyond first-line platinum-based chemotherapy. Immunotherapy has emerged as a viable option for many cancers with a similar unmet need. Therefore, we reviewed current understanding of the tumor immune microenvironment and recent advances in cellular immunotherapy and therapeutic cancer vaccines against BTC. We illustrated the efficacy of dendritic cell vaccination in one patient with advanced, chemorefractory, melanoma-associated antigen (MAGE)-positive gallbladder carcinoma, who was given multiple injections of an allogenic MAGE antigen-positive melanoma cell lysate (MCL)-based autologous dendritic cell vaccine combined with sequential anti-angiogenic therapy. This resulted in good radiological and tumor marker response and an overall survival of 3 years from diagnosis. We postulate the potential synergism of adding anti-angiogenic therapy, such as bevacizumab, to immunotherapy in BTC, as a rational scientific principle to positively modulate the tumor microenvironment to augment antitumor immunity.


Long-Term Clinical Outcomes of Nonhyperemic Pressure Ratios: Resting Full-Cycle Ratio, Diastolic Pressure Ratio, and Instantaneous Wave-Free Ratio.
Background Nonhyperemic pressure ratios (NHPRs) such as instantaneous wave-free ratio, resting full-cycle ratio, or diastolic pressure ratio have emerged as invasive physiologic indices precluding the need for hyperemic agents. The current study sought to evaluate the long-term prognostic implications of NHPRs compared with fractional flow reserve (FFR). Methods and Results NHPRs were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The association between NHPRs and the risk of 5-year vessel-oriented composite outcomes (VOCO, a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven revascularization) were analyzed among 864 deferred vessels. Lesions with positive NHPRs (instantaneous wave free ratio, resting full-cycle ratio, and diastolic pressure ratio ≤0.89) or FFR (≤0.80) showed significantly higher risk of VOCO at 5 years than those with negative NHPRs or FFR, respectively. Discriminant ability for 5-year VOCO was not different among NHPRs and FFR (C-index: 0.623-0.641, P for comparison=0.215). In comparison of VOCO among the groups with deferred concordant negative (NHPRs-/FFR-), deferred discordant (NHPRs+/FFR- or NHPRs-/FFR+), and revascularized vessels, the cumulative incidence of VOCO were 7.5%, 14.4%, and 14.8% (log-rank P<0.001), respectively. The deferred discordant group showed similar risk of VOCO with the revascularized vessel group (hazard ratio, 0.981; 95% CI 0.434-2.217, P=0.964). Conclusions Currently available invasive pressure-derived indices showed similar prognostic implications for vessel-related events at 5 years. Deferred lesions with discordant results between NHPRs and FFR did not show higher risk of vessel-related events at 5 years than revascularized vessels. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01621438, NCT01621438.


A New Species of Morelacarus (Acariformes: Prostigmata: Leeuwenhoekiidae) Associated With Sceloporus grammicus (Squamata: Phrynosomatidae) From the Mexican Plateau, Zacatecas, Mexico.
A new species of chigger mites, Morelacarus uazi n. sp., parasitizing lizards of the species Sceloporus grammicus from Mazapil, Zacatecas, Mexico, is described and illustrated. This new taxon differs from other species of the genus by having a palpal claw with 4 subequal paired prongs, and it can be further distinguished by the combination of the following characters: presence of onychotriches and mastitarsala III, absence of mastitibiala III, subterminala I, and parasubterminala I, and the palpal setal formula B/B/BBb. Additionally, an identification key for the species of the genus Morelacarus is presented. The new species represents the seventh species assigned to the genus and the first species described from a Mexican lizard.


Effects of low intrapulmonary PCO2 on ventilatory sensitivity to PaCO2 in chickens.
We found conflicting reports regarding the relationship between intrapulmonary PCO2 and sensitivity to PaCO2 in the chicken. To resolve this, we anesthetized eight cockerels with sodium pentobarbital (25-35 mg/kg), cannulated the cutaneous ulnar vein and carotid artery, opened the thorax and ventilated right and left lungs independently. We established PaCO2 by over-ventilating the denervated, perfused right lung with the following: 94.7, 39.9, 31.6 and 19.0 Torr PCO2 balanced with oxygen. At each right lung CO2 tension (PRCO2), we measured blood pressure and ventilatory responses to five CO2 tensions (PLCO2) ventilating the non-perfused left lung. PLCO2 ranged from 70.3 to 15.7 Torr. We found a linear relationship between the amplitude of sternal deflections and PaCO2-1, and that the slope depended upon PLCO2. Respiratory period was also linearly related to PaCO2-1, however the intercept, not the slope, was a altered by PLCO2. Stepwise regression analyses revealed an important interaction term (that is, (PaCO2.PLCO2)-1) in the determination of respiratory amplitude, but not in the determination of period. We conclude that low intrapulmonary PCO2 enhances the sensitivity of respiratory amplitude to changes in PaCO2. Further, we propose that intrapulmonary chemoreceptor discharge mediates this change in sensitivity to PaCO2.


Two new species of the primitively segmented spider genus Liphistius Schiödte, 1849 (Mesothelae, Liphistiidae) from Myanmar.
Two Liphistius species of the primitively segmented spider family Liphistiidae, collected from Loikaw (Kayah State) and Pinlaung (Shan State), Myanmar, are diagnosed and described as new to science based on their genital morphology: Liphistius hpruso sp. nov. (♀), Liphistius pinlaung sp. nov. (♂♀).


Routes of excretion of neuronal lysosomal dense bodies after ventricular infusion of leupeptin in the rat: a study using ubiquitin and PGP 9.5 immunocytochemistry.
To determine the rate and routes of removal of lysosomal, lipofuscin-like dense bodies from neurons, the protease inhibitor, leupeptin, was infused into the lateral ventricle of rats for up to nine days. After seven days a number of animals were then allowed to recover. The formation and later disappearance of dense bodies was followed by morphology and immunocytochemistry. After 48 h of infusion lysosomal dense bodies in large numbers appeared in cortical, hippocampal and cerebellar neurons, which also showed increased ubiquitin immunoreactivity, as well as in other cell types. By 3-4 days ubiqutin-immunoreactive dense bodies were equally distributed between neurons and astroglia. After seven to nine days of infusion ubiquitin immunoreactive dense bodies filled neuronal perikarya, dendrites and expanded initial segments of many axons and were abundant in glial processes. All dense bodies studied by electron microscopy were ubiquitin immunoreactive. After four days of recovery dense bodies were markedly fewer in neuronal perikarya, and virtually all were now within glial processes. From 7 to 28 days of recovery, when most neurons appeared normal, lipofuscin bodies remained in axon initial segments and in reduced numbers in glial processes, particularly around blood vessels and beneath the pia of hippocampus and of cerebellar cortex. Thus, neurons probably have a steady passage of short lived proteins through the lysosomal excretory pathway. The observed temporal sequence of events on recovery suggests that secondary lysosomes probably pass rapidly from neuronal perikarya and dendrites to astrocytes and thus to the vascular bed or pia-arachnoid. The mechanism of cell-to-cell transfer is not clear from this study.


SARS-CoV-2 infection in kidney transplant recipients: Experience of the italian marche region.
Infection related to Coronavirus-19 (CoV-2) is pandemic affecting more than 4 million people in 187 countries worldwide. By May 10, 2020, it caused more than 280 000 deaths all over the world. Preliminary data reported a high prevalence of CoV-2 infection and mortality due to severe acute respiratory syndrome related CoV-2 (SARS-CoV-2) in kidney-transplanted patients (KTRs). Nevertheless, the outcomes and the best treatments for SARS-CoV-2-affected KTRs remain unclear. In this report, we describe the clinical data, the treatments, and the outcomes of 5 KTRs with SARS-CoV-2 admitted to our hospital in Ancona, Marche region, Italy, from March 17 to present. Due to the severity of SARS-CoV-2, immunosuppression with calcineurin inhibitors, antimetabolites, and mTOR-inhibitors were stopped at the admission. All KTRs were treated with low-dose steroids. 4/5 KTRs were treated with hydroxychloroquine. All KTRs received tocilizumab up to one dose. Overall, the incidence of SARS-CoV-2 in KTRs in the Marche region was 0.85%. 3/5 were admitted in ICU and intubated. One developed AKI with the need of CRRT with Cytosorb. At present, two patients died, two patients were discharged, and one is still inpatient in ICU. The critical evaluation of all cases suggests that the timing of the administration of tocilizumab, an interleukin-6 receptor antagonist, could be associated with a better efficacy when administered in concomitance to the drop of the oxygen saturation. Thus, in SARS-CoV-2-affected KTRs, a close biochemical and clinical monitoring should be set up to allow physicians to hit the virus in the right moment such as a sudden reduction of the oxygen saturation and/or a significant increase in the laboratory values such as D-dimer.


Adjuvant endocrine therapy for the surgeon: options, side effects, and their management.
Adjuvant endocrine therapy is often advised for women with hormone receptor positive breast cancer. In premenopausal women, tamoxifen is the primary endocrine therapy option since aromatase inhibitors (AIs) are contraindicated in patients with residual ovarian function. The benefit of ovarian ablation/suppression in premenopausal patients remains controversial. In postmenopausal ER positive patients, treatment with an AI alone, switching strategies with an AI and tamoxifen, or extended therapy with an AI after 5 years of tamoxifen are superior to 5 years of tamoxifen alone. While the data supporting the use of endocrine therapy for ER positive breast cancer is clear, adverse effects occur with variable frequency and severity. The intensity and severity of the most common endocrine therapy adverse effects are mild to moderate for the majority of women, and serious life-threatening adverse effects are uncommon. However, compliance issues are often larger than recognized. Good communication with patients is critical to address concerns and symptoms, and more research is needed to identify effective methods to minimize treatment side effects.


A uniaxially oriented nanofibrous cellulose scaffold from pellicles produced by Gluconacetobacter xylinus in dissolved oxygen culture.
An aerobic, Gram-negative bacterium, Gluconacetobacter xylinus, was successfully employed to produce a stretchable cellulose nanofiber pellicle using dissolved oxygen in a conventional cultured medium. The obtained nanofibers were highly crystalline with the metastable cellulose Iα phase being apparently the dominant phase by more than 90%. The obtained pellicle could be stretched by up to 1.5 times to provide oriented crystalline nanofibrous films. Low heating of the nanofibrous film induced the transformation of the dominant cellulose Iα crystalline phase into the Iβ crystalline phase without a loss of crystallinity or the high Young's modulus. The film also exhibited unique and anisotropic viscoelastic and mechanical properties as well as superior thermal stability compared with conventional high-performance synthetic polymeric materials. In addition, when G. xylinus cells were transferred to the oriented surface after stretched, they started to synthesize cellulose ribbons that parallel the nanofiber orientation of the substrate. This function as a template was evidenced by direct video imaging of the motion of the bacteria. The application of a bacterial culture using dissolved oxygen in the medium offers the fabrication of novel anisotropic and nanofibrous scaffold of cellulose Iα.


The daily swab test collection problem.
Digital Contact Tracing (DCT) has been proved to be an effective tool to counteract the new SARS-CoV-2 or Covid-19. Despite this widespread effort to adopt the DCT, less attention has been paid to the organisation of the health logistics system that should support the tracing activities. Actually, the DCT poses a challenge to the logistics of the local health system in terms of number of daily tests to be collected and evaluated, especially when the spreading of the virus is soaring. In this paper we introduce a new optimisation problem called the Daily Swab Test Collection (DSTC) problem, that is the daily problem of collecting swab tests at home in such a way to guarantee a timely testing to people notified by the app to be in contact with a positive case. The problem is formulated as a variant of the team orienteering problem. The contributions of this paper are the following: (i) the new optimisation problem DSTC that complements and improves the DCT approach proposed by Ferretti et al. (Science 10.1126/science.abb6936, 2020), (ii) the DSCT formulation as a variant of the TOP and a literature review highlighting that this variant can have useful application in healthcare management, (iii) new realistic benchmark instances for the DSTC based on the city of Turin, (iv) two new efficient and effective hybrid algorithms capable to deal with realistic instances, (v) the managerial insights of our approach with a special regard on the fairness of the solutions. The main finding is that it possible to optimise the underlying logistics system in such a way to guarantee a timely testing to people recognised by the DCT.


Suppression of adiponectin receptor 1 promotes memory dysfunction and Alzheimer's disease-like pathologies.
Recent studies on neurodegeneration have focused on dysfunction of CNS energy metabolism as well as proteinopathies. Adiponectin (ADPN), an adipocyte-derived hormone, plays a major role in the regulation of insulin sensitivity and glucose homeostasis in peripheral organs via adiponectin receptors. In spite of accumulating evidence that adiponectin has neuroprotective properties, the underlying role of adiponectin receptors has not been illuminated. Here, using gene therapy-mediated suppression with shRNA, we found that adiponectin receptor 1 (AdipoR1) suppression induces neurodegeneration as well as metabolic dysfunction. AdipoR1 knockdown mice exhibited increased body weight and abnormal plasma chemistry and also showed spatial learning and memory impairment in behavioural studies. Moreover, AdipoR1 suppression resulted in neurodegenerative phenotypes, diminished expression of the neuronal marker NeuN, and increased expression and activity of caspase 3. Furthermore, AD-like pathologies including insulin signalling dysfunction, abnormal protein aggregation and neuroinflammatory responses were highly exhibited in AdipoR1 knockdown groups, consistent with brain pathologies in ADPN knockout mice. Together, these results suggest that ADPN-AdipoR1 signalling has the potential to alleviate neurodegenerative diseases such as Alzheimer's diseases.


MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction.
Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.


The chromosomal location of genes for elongation factor Tu and ribosomal protein S10 in the cyanobacterium Spirulina platensis provides clues to the ancestral organization of the str and S10 operons in prokaryotes.
The structural gene (rps10) encoding ribosomal protein S10 of the cyanobacterium Spirulina platensis has been localized both on chromosomal DNA and the previously characterized recombinant plasmid pSp7 harbouring the 3'-terminal portion of the gene for elongation factor G (fus) and the gene for elongation factor Tu (tuf). Alignment of the predicted S10 sequence of S. platensis with the homologous sequences from cyanelles, bacteria, archaea and eukarya showed that the cyanobacterial S10 shares a high degree of sequence homology (74% amino acid identity) with the cyanellar protein. Unlike the situation in Escherichia coli, the rps10 gene of S. plantensis is unlinked to the S10 operon genes, being adjacent to the str operon genes. Since a similar organization could be observed in cyanelles of Cyanophora paradoxa and in all archaea so far analysed, this probably represents the ancestral state.


Performance comparison of vibration devices on orthodontic tooth movement - A systematic review and meta-analysis.
To evaluate the efficiency of vibratory devices in altering rate of orthodontic tooth movement. A literature search up to January 31, 2020 was conducted in three electronic databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and Science Direct, to identify studies on vibratory devices reporting any alteration in tooth movement as a primary outcome. Only articles published in English language were included. A meta-analysis was done to compare the amount of tooth movement (in mm) in patients treated with vibratory devices compared to control groups, to quantify weighted treatment effects. A total of two split mouth studies, six parallel arm randomized control trials (RCT) one split mouth RCT, and three regular RCTs were assessed qualitatively. Quantitative assessment was done for 8 randomized trials using a forest plot (310 patients). Pooled data showed increase in the amount of tooth movement by 0.34 mm (95% CI:0.25,0.42). There was a statistically significant difference noted for this result at p < 0.00001. Current evidence suggests a moderate to high level of certainty in regard to included studies in this systematic review and meta-analysis. Vibratory devices when used in conjunction with fixed orthodontic appliances show significant increase in the rate of tooth movement. These devices can be used by clinicians to reduce treatment duration and patient discomfort. CRD42020169675.


Long-term follow-up of a vaccination program for infants born to HBsAg-positive mothers in Stockholm County, Sweden.
We investigated the long-term antibody response to hepatitis B virus (HBV) vaccination in babies born to chronically infected mothers. They received one dose of monovalent HBV vaccination at birth and one month of age, followed by 3 doses of hexavalent vaccine including an HBV component at ages 3, 5, and 12 months, respectively, with a very high percentage of protective anti-HBs levels at 13 months. At the age of 8-12 years, 56 out of 68 children (82%) had protective levels of anti-HBs, two had signs of anti-HBc seroconversion without any history of clinical disease and none had ongoing infection. A small subgroup was retested after one booster dose, in all resulting in increase in anti-HBs from below 10 IU/L to levels corresponding to protective immunity. We conclude that this vaccination strategy is effective throughout the first decade of life in avoiding chronic infection and in maintaining a good serological response.


Gamblers' beliefs about responsibility for minimizing gambling harm: Associations with problem gambling screening and gambling involvement.
Increasingly, gambling stakeholders communicate that minimizing gambling harm is a shared societal responsibility. Individual gamblers' beliefs about responsibility for minimizing gambling harm are worthy of study because these beliefs might influence gambling behavior. In this study, using a sample of casino loyalty program subscribers (N = 4,795), we observed that respondents who had a positive result on a brief gambling disorder screen were more likely than those who screened negative to hold seven stakeholder groups (i.e., scientists, clinicians, casino employees, government regulators, public health officials, casino industry lobbyists, public safety officials) responsible for helping to minimize gambling harm. The sum of stakeholder groups held responsible for minimizing gambling harm, along with beliefs that casinos share responsibility for encouraging responsible gambling behavior, predicted gambling disorder screening status after controlling for established problem gambling risk factors. These results replicated our previous study using a mostly independent sample. Contrary to our expectations, beliefs about responsibility for mitigating gambling harm were mostly unrelated to measures of gambling involvement. These results provided additional support for the notion that those who are at risk for gambling harm are especially likely to hold others responsible for minimizing such harm. However, they call into question the role of gambling involvement in this relationship.


Microalgal conversion of whey and lactose containing substrates: current state and challenges.
Currently dairy processing by-products, such as whey, still propose a significant threat to the environment if unproperly disposed. Microalgal bioconversion of such lactose containing substrates can be used for production of valuable microalgae-derived bio-products as well as for significant reduction of environmental risks. Moreover, it could significantly reduce microalgae biomass production costs, being a significant obstacle in commercialization of many microalgae species. This review summarizes current knowledge on the use of lactose containing substrates, e.g. whey, for the production of value-added products by microalgae, including information on producer cultures, fermentation methods and cultivation conditions, bioprocess productivity and ability of microalgal cultures to produce β-galactosidases. It can be stated, that despite several limitations lactose-containing substrates can be successfully used for both-the production of microalgal biomass and removal of high amounts of excess nutrients from the cultivation media. Moreover, co-cultivation of microalgae and other microorganisms can further increase the removal of nutrients and the production of biomass. Further investigations on lactose metabolism by microalgae, selection of suitable strains and optimisation of the cultivation process is required in order to enable large-scale microalgae production on these substrates.


[CD14 genomic polymorphism influences CD14 expression in whole blood culture].
To investigate whether -159C/T promoter polymorphism of the CD14 gene influences the CD14 expression as well as release in whole blood culture. One hundred and eighteen healthy human blood donors were included in the present study. CD14 mRNA expression and soluble CD14 levels were measured using a whole blood cell culture model with or without lipopolysaccharide (LPS) stimulation. The CD14 gene polymorphism was determined by polymerase chain reaction and subsequent HaeIII restriction enzyme digestion of the polymerase chain reaction products. TNF-alpha production in the whole blood culture was also measured. Among the 118 individuals, there were 40 subjects homozygous for the T allele (TT), 62 were heterozygous (CT), and 16 had the genotype CC. The CD14 mRNA expression in leukocytes and soluble CD14 levels in supernatant were higher in TT homozygotes and carriers of the genotype TC compared with individuals homozygous for the C allele (P < 0.05 or 0.01). In addition, the highest values of TNF-alpha production were found in TT homozygote [(352 +/- 215) pg/ml] compared with both genotype TC and CC [(261 +/- 163) pg/ml, (198 +/- 122) pg/ml, both P < 0.05]. The -159C/T promoter polymorphism of the LPS receptor CD14 may influence the CD14 expression as well as release in whole blood culture, and it might be associated with TNF-alpha response to LPS stimulation.


Simulation of CAD/CAM milling on lithium disilicate: Mechanical and topographic analyses of surface grinding different protocols.
The aim of this study was to evaluate the topography and the fatigue performance of lithium disilicate glass-ceramic after surface grinding through different laboratory protocols used to simulate the Computer-aided design/Computer-aided manufacturing (CAD/CAM) milling. Ceramic discs (IPS e.max CAD, Ø = 13.5 mm × 1.2 mm of thickness) were produced through different methodologies: milling in CAD/CAM system (CAD/CAM group); produced in-lab with a polished surface (POL group); or produced through in-lab methods and randomly distributed into five groups according to different grinding protocols to simulate the CAD/CAM milling [grinding with a CAD/CAM bur coupled to a mandrel (CAD/CAM Bur group); fine diamond bur using oscillatory movements (DBO group); fine diamond bur in x and y axes of the disc (DBXY group); #60-grit silicon carbide sandpaper (SiC group); and #60-grit wood sandpaper (WS group)]. The specimens were fatigue tested (n = 15) according to the step-stress method (initial load: 60 N; step-size: 20 N; 10,000 cycles/step; 20 Hz frequency). A roughness analysis was performed on all specimens, while fractal dimension (FD) and fractography were performed on representative samples. The Kaplan-Meier analysis showed that the POL (293.3 N) group presented better fatigue performance (higher load and number of cycles for failure) (p < 0.05) than the other groups (CAD/CAM = 222.7 N; CAD/CAM Bur = 181.3 N; DBO = 184.0 N; DBXY = 192.0 N; SiC = 182.6 N; WS = 182.6 N). For roughness, only the SiC (Ra = 1.616; Rz = 10.465) and WS (Ra = 1.673; Rz = 10.655) groups produced statistically similar Ra (μm) and Rz (μm) values to the CAD/CAM (Ra = 1.628; Rz = 9.571) group (p > 0.05). The surface created by CAD/CAM milling and POL group exhibited more complexity (FD) higher values than the experimental groups. For the ceramic surface topography images, the CAD/CAM milling visibly produced a uniform surface compared to the other groups; however, the POL group was the smoothest. The DBO, DBXY, SiC, and WS groups resulted in similar characteristics of surface topography. Therefore, although the SiC and WS groups showed similar roughness to the control group (CAD/CAM), no in-lab simulation method was fully capable to mimic the mechanical performance of the CAD/CAM-milled lithium disilicate glass-ceramic.


Cell labeling approaches for fluorescence-based in vivo flow cytometry.
We provide an overview of the methods used to label circulating cells for fluorescence detection by in vivo flow cytometry. These methods are useful for cell tracking in small animals without the need to draw blood samples and are particularly useful for the detection of circulating cancer cells and quantification of circulating immune cells.


Amputee locomotion: spring-like leg behavior and stiffness regulation using running-specific prostheses.
Carbon fiber running-specific prostheses (RSPs) have allowed individuals with lower extremity amputation (ILEA) to participate in running. It has been established that as running speed increases, leg stiffness (Kleg) remains constant while vertical stiffness (Kvert) increases in able-bodied runners. The Kvert further depends on a combination of the torsional stiffnesses of the joints (joint stiffness; Kjoint) and the touchdown joint angles. Thus, an increased understanding of spring-like leg function and stiffness regulation in ILEA runners using RSPs is expected to aid in prosthetic design and rehabilitation strategies. The aim of this study was to investigate stiffness regulation to various overground running speeds in ILEA wearing RSPs. Eight ILEA performed overground running at a range of running speeds. Kleg, Kvert and Kjoint were calculated from kinetic and kinematic data in both the intact and prosthetic limbs. Kleg and Kvert in both the limbs remained constant when running speed increased, while intact limbs in ILEA running with RSPs have a higher Kleg and Kvert than residual limbs. There were no significant differences in Kankle, Kknee and touchdown knee angle between the legs at all running speeds. Hip joints in both the legs did not demonstrate spring-like function; however, distinct impact peaks were observed only in the intact leg hip extension moment at the early stance phase, indicating that differences in Kvert between limbs in ILEA are due to attenuating shock with the hip joint. Therefore, these results suggest that ILEA using RSPs has a different stiffness regulation between the intact and prosthetic limbs during running.


Study on sperm function in men long after cessation of gossypol treatment.
Sperm function was assessed in 19 men 3-10 years after cessation of gossypol treatment and 2-9 years after recovery of normal sperm density. Nineteen normal fertile men of similar age served as the controls. The zona-free hamster egg-sperm penetration assay (SPA) revealed a highly significant difference (P less than 0.01) in the penetration rates between the treated and the control groups. Hormone assays indicated that there were no significant differences in circulating levels of luteinizing hormone (LH) and testosterone (T) between the two groups, but the follicle stimulating hormone (FSH) level of the treated group was significantly higher than that of the controls (P less than 0.05). The results showed that sperm function in the treated group was lower than that in the control, which may be a result of persistent gossypol-mediated damage to the testes.


Haemostasis, inflammation and renal function following exercise in patients with intermittent claudication on statin and aspirin therapy.
Previous studies have suggested that exercise in patients with intermittent claudication (IC) may induce a systemic thrombo-inflammatory response. The effect of secondary prevention therapy on this response is unknown. This study aimed to investigate the effects of treadmill exercise on markers of coagulation activation, inflammation and renal function in patients with IC, receiving aspirin and statin therapy compared to healthy controls. Samples were taken before, immediately and 1 hour after exercising on a treadmill in 20 patients with IC and 20 healthy volunteers. Interleukin-6 (IL-6), thrombin-anti-thrombin complex (TAT) and fibrin D-dimer were measured by ELISA. High sensitivity CRP (HsCRP) and urinary albumin were measured via a nephelometric technique, urinary protein via a turbidometric assay and N-acetyl-beta-D-glucosaminidase (NAG) via a colorimetric assay. Elevated baseline levels of Hs-CRP, IL-6, white cell counts, D-dimer and urinary NAG occurred in patients with IC compared to volunteers (p > 0.05). Following exercise there was no increase in Hs CRP or IL-6. D-dimer levels significantly increased following exercise in the patients and volunteers. TAT levels increased immediately after exercise in the patient group only and were significantly increased at 1 hour in both patients and volunteers. A transient rise in the protein creatinine ratio occurred in both groups (p < 0.007), and in albumin creatinine ratio in the patient group. There was no change in urinary NAG. Elevated markers of inflammation occurred in patients with IC on statin and aspirin therapy but these did not increase following exercise. However, acute exercise resulted in a prothrombotic state evident in both groups, although this was more prolonged in patient with IC. The clinical significance of these findings in patients who are known to be at an increased risk of cardiac and other thrombotic event are unclear.


Patients with hepatitis C infection and normal liver function: an evaluation of cognitive function.
Hepatitis C virus (HCV) is associated with neuropsychiatric complaints. Previous studies have associated cognitive alterations with HCV infection but have often included confounding factors in their samples. This study compares the cognitive performance between patients with HCV infection (HCV patients) and a control group while excluding other factors that may cause cognitive impairment. This cross-sectional study was conducted from March 2010 through June 2011. HCV infected patients and healthy individuals between the ages of 18 and 80 years were considered eligible. The exclusion criteria included well established causes of cognitive impairment such as depression and cirrhosis. Study participants underwent neuropsychological testing involving measures of attention, memory, abstraction, visuoconstructive abilities, and executive function. Of 138 initial patients, 47 were excluded because of their medical records, three refused to participate, 23 did not attend the consultation, and 32 were excluded because of having Beck Depression Inventory (BDI) scores >11. In all, 33 patients underwent neuropsychological testing; however, three were excluded because of having hypothyroidism, and one was excluded because of having a cobalamin deficiency. For the control group, of the 33 healthy individuals that were selected, four were excluded because of having BDI scores >11. Thus, the final analysis included 29 HCV patients and 29 control participants. The groups did not differ in education, age, or gender. No statistically significant differences were found between the groups regarding cognitive performance. In this study using strict selection criteria, there was no evidence of an association between HCV infection and cognitive impairment.


Children and adolescents' preferences for support when living with a dying parent - An integrative review.
To identify and synthesize the evidence base regarding children and adolescents' preferences for support when living with a dying parent. Integrative literature review study. Searches were conducted in PubMed, CINAHL, PsycINFO, the Cochrane Library, Sociological Abstracts and Scopus, between 1 October 2019 and May 2021. Data were analysed and synthesized using integrative thematic analysis according to the analysis stages specified by Whittermore and Knafl. Twenty-two articles were identified. Children and adolescents' preferences for support were described through one overarching theme, Striving to achieve control and balance, together with six subthemes; "Involvement in the sick parent's care and treatment"; "Wanting to be with the sick parent but needing respite"; "Information must be continuous and individually adapted"; "emotional and communicative support from parents and family members"; "professional, compassionate and informative support"; and "support in friendships and opportunities to maintain normality."


Circular RNA translation: novel protein isoforms and clinical significance.
In recent years, significant attention has focused on circular RNA (circRNA) translation to determine its clinical significance. Cap-independent translation of circRNAs driven by an internal ribosome entry site (IRES) or an N6-methyladenosine (m6A)-containing short sequence is different from the canonical cap-dependent translation of linear mRNAs. New proteins or isoforms possessing novel physiological roles can be generated from translatable circRNAs. The present review describes the elements involved in circRNA translation, and the functions of the translated novel protein isoforms in human diseases. Bifunctional characteristics of translatable circRNAs exerted by the circRNAs and the translated proteins are also discussed. Furthermore, various molecular strategies that could be used as appropriate therapeutic options are proposed.


Coagulum pyelolithotomy.
The interest shown in a coagulum pyelolithotomy technique reported at a recent urologic meeting has prompted this preliminary communication. It was not possible to follow the methodology recently reported using the fibrinogen preparation available in Canada. This led to the development of the simpler technique described in this report which has been used in 3 cases to date. In all cases all calculi were easily extracted. Using the coagulum, considerable operating room time was saved and renal instrumentation was minimized.


Adult aqueductal stenosis presenting as double incontinence: a case report with magnetic resonance imaging.
An unusual case of adult-onset aqueduct stenosis is discussed. The patient presented with a 3-year history of bowel and bladder incontinence without associated dementia, gait disturbance, headache, visual loss, or hypothalamic dysfunction. The absence of the midportion of the sylvian aqueduct in this patient is verified by magnetic resonance imaging.


Effects of hepatic fibrosis on ofloxacin pharmacokinetics in rats.
The purpose of the present work was to study the pharmacokinetics of ofloxacin, a poorly metabolised drug, in experimental hepatic fibrosis. The possible roles of small intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) in the bioavailability of ofloxacin were also evaluated. Rat hepatic fibrosis model was successfully induced using complex factors including carbon tetrachloride, ethanol and high fat. After rats received a single oral or intravenous dose of ofloxacin (40 mg kg(-1)), the plasma concentrations of ofloxacin were monitored at the scheduled time using spectrofluorimetric assay. Plasma concentration-time profiles were comodeled using compartmental method. Meanwhile, microsomal CYP isoenzymatic levels and P-gp expression in small intestines were compared between normal and hepatic fibrosis rats. When ofloxacin was administered intravenously, C(max) and the distribution half-life increased significantly in comparison with normal group, whereas the distribution rate constants, the apparent volume of distribution decreased. Oral ofloxacin bioavailability was significantly altered in hepatic fibrosis rats. AUC and C(max) were reduced, while the absorption half-life, peak time and elimination half-life significantly were prolonged, suggesting that both the extent and the rate of ofloxacin absorption were decreased. Furthermore, the increases in the levels of microsomal ethoxyresorufin O-deethylase and erythromycin N-demethylase were accompanied with up-regulation of mdr 1a mRNA in the small intestines of hepatic fibrosis rats when compared to those of the normal rats. The Results showed that pharmacokinetics of ofloxacin could be altered in hepatic fibrosis. Up-regulated P-gp expression and increased CYP isoenzymatic activities of small intestines in hepatic fibrosis rats may contribute to the decreased bioavailability and increased elimination of ofloxacin after oral administration.


Harmful effects of dietary salt in addition to hypertension.
In addition to raising the blood pressure dietary salt is responsible for several other harmful effects. The most important are a number which, though independent of the arterial pressure, also harm the cardiovascular system. A high salt intake increases the mass of the left ventricle, thickens and stiffens conduit arteries and thickens and narrows resistance arteries, including the coronary and renal arteries. It also increases the number of strokes, the severity of cardiac failure and the tendency for platelets to aggregate. In renal disease, a high salt intake accelerates the rate of renal functional deterioration. Apart from its effect on the cardiovascular system dietary salt has an effect on calcium and bone metabolism, which underlies the finding that in post-menopausal women salt intake controls bone density of the upper femur and pelvis. Dietary salt controls the incidence of carcinoma of the stomach and there is some evidence which suggests that salt is associated with the severity of asthma in male asthmatic subjects.


Establishment of drug screening in human embryonic stem cells based on a high-content screening system.
High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g., Oct-4) prior to HCS, which can be time consuming and labor intensive. In this study, we employed transgenic hESCs with enhanced green fluorescent protein driven by stemness gene Oct-4 promoter (Oct-4-EGFP-H9), in which the colony area and relative green fluorescence area inferred a state of hESC proliferation and stemness, respectively. The Oct-4-EGFP-H9 transgenic hESCs were cultured in mTeSR medium with different concentrations of 5-Fluorouracil (5-FU), vitamin C (VC), or retinoic acid (RA) for 5-7 days, followed by repeated imaging using the HCS system. Finally, the hESC colony area and green fluorescence area were calculated. Results showed that 5-FU treatment markedly reduced colony area in a dose-dependent manner, whereas VC and RA treatments did not. MTT assay and flow cytometry indicated that 5-FU inhibited the proliferation of hESCs significantly, verifying reliability of the data from the HCS system based on colony area analysis. The green fluorescence to total colony area ratio decreased with RA treatment, suggesting that RA significantly promoted differentiation, whereas 5-FU and VC had almost no effect, as verified by quantitative real-time polymerase chain reaction and western blot analysis. In conclusion, our study established a rapid and efficient drug screening system without the requirement of staining based on HCS.


Serum levels of cystatin C in patients with malignancy.
Serum levels of cystatin C have been proposed to be an ideal marker of the glomerular filtration rate (GFR). However, some reports have shown that serum levels of cystatin C increase independently of GFR. In this study, we evaluated the clinical utility of cystatin C in monitoring GFR, especially in patients with a malignancy. Study subjects consisted of 82 patients with a malignancy, 39 patients with a non-malignancy, 31 healthy volunteers, and 206 patients with various degrees of renal function. We measured serum cystatin C, beta2-microglobulin (beta 2mG), and creatinine (CRE) levels in all patients. Serum CRP levels were measured in 21 patients with a malignancy and 28 patients with a non-malignancy whose creatinine clearance (Ccr) was > or =70 ml/min. Cystatin C, beta 2mG, and CRP were measured by immune nephelometry and CRE was measured by an enzyme assay. In patients with a malignancy, regression analysis yielded the equation: 1/cystatin C = 0.06 x Ccr + 0.710, correlation coefficient, r, of 0.33. The r was significantly lower than in patients with various degrees of renal function. There were no significant differences when the r performed on beta 2mG and CRE was compared between the same groups of patients. In 74 patients with a malignancy, in whom serum CRE levels were < or =1.1 mg/dl, increased levels of cystatin C were observed in 25 patients and increased levels of beta 2mG were observed in 39 patients. In comparing patients with a malignancy and a non-malignancy, the number of patients with an increased level of cystatin C, despite a Ccr > or = 70 ml/min (8/33) or a CRE < or = 1.1 mg/dl (13/41), was larger in the former group than the latter group, although the result was not statistically significant. Similarly, the number of patients with an increased level of beta 2mG, despite a Ccr > or = 70 ml/min or a CRE < or = 1.1 mg/dl was significantly larger in the former group compared to the latter group. Regression analysis between the serum levels of cystatin C and CRP in patients with a malignancy whose Ccr were > or =70 ml/min had a weak correlation (r = 0.31). The results of our study suggest that the serum levels of cystatin C are not always a reliable marker of the GFR in patients with a malignancy, probably in relation to its nature as a cysteine protease inhibitor.


Well-oriented ZZ-PS-tag with high Fc-binding onto polystyrene surface for controlled immobilization of capture antibodies.
The site specificity and bioactivity retention of antibodies immobilized on a solid substrate are crucial requirements for solid phase immunoassays. A fusion protein between an immunoglobulin G (IgG)-binding protein (ZZ protein) and a polystyrene-binding peptide (PS-tag) was constructed, and then used to develop a simple method for the oriented immobilization of the ZZ protein onto a PS support by the specific attachment of the PS-tag onto a hydrophilic PS. The orientation of intact IgG was achieved via the interaction of the ZZ protein and the constant fragment (Fc), thereby displayed the Fab fragment for binding antigen. The interaction between rabbit IgG anti-horseradish peroxidase (anti-HRP) and its binding partner HRP was analyzed. Results showed that the oriented ZZ-PS-tag yielded an IgG-binding activity that is fivefold higher than that produced by the passive immobilization of the ZZ protein. The advantage of the proposed immunoassay strategy was demonstrated through an enzyme-linked immunosorbent assay, in which monoclonal mouse anti-goat IgG and HRP-conjugated rabbit F(ab')2 anti-goat IgG were used to detect goat IgG. The ZZ-PS-tag presented a tenfold higher sensitivity and a wider linear range than did the passively immobilized ZZ protein. The proposed approach may be an attractive strategy for a broad range of applications involving the oriented immobilization of intact IgGs onto PS supports, in which only one type of phi-PS (ZZ-PS-tag) surface is used.


Effect of membrane character and solution chemistry on microfiltration performance.
To help understand and predict the role of natural organic matter (NOM) in the fouling of low-pressure membranes, experiments were carried out with an apparatus that incorporates automatic backwashing and long filtration runs. Three hollow fibre membranes of varying character were included in the study, and the filtration of two different surface waters was compared. The hydrophilic membrane had greater flux recovery after backwashing than the hydrophobic membranes, but the efficiency of backwashing decreased at extended filtration times. NOM concentration of these waters (7.9 and 9.1mg/L) had little effect on the flux of the membranes at extended filtration times, as backwashing of the membrane restored the flux to similar values regardless of the NOM concentration. The solution pH also had little effect at extended filtration times. The backwashing efficiency of the hydrophilic membrane was dramatically different for the two waters, and the presence of colloid NOM alone could not explain these differences. It is proposed that colloidal NOM forms a filter cake on the surface of the membranes and that small molecular weight organics that have an adsorption peak at 220nm but not 254nm were responsible for "gluing" the colloids to the membrane surface. Alum coagulation improved membrane performance in all instances, and this was suggested to be because coagulation reduced the concentration of "glue" that holds the organic colloids to the membrane surface.


Functional State of Various Types of Regenerative-Competent Neural Tissue Cells in β-Amyloid-Induced Neurodegeneration.
We analyzed the content and functional activity of various types of regenerative-competent cells of the subventricular zone of the cerebral hemispheres in experimental mice under conditions of in vitro modeling of β-amyloid-induced neurodegeneration. Fundamentally different (opposite) effects of β-amyloid on functional activity of multipotent neural stem cells (NSC) and neuronal committed progenitors (NCP) were revealed. β-Amyloid suppressed proliferation of NSC and stimulated their differentiation. At the same time, an increase in the mitotic activity of NCP was observed with a decrease in the intensity of their specialization. These changes in the functioning of progenitor cells developed against the background of a significant drop in the production of neurotrophic growth factors by neuroglia. These phenomena indicate marked discoordination of the activity of regenerative-competent cells of various types.


Influence of hypophysectomy on dopamine receptors and dopaminergic behaviors.
Hypophysectomy (Hypox) has been proposed to alter the behavioral and biochemical indices of striatal dopamine (DA) function. Since the regulation of striatal DA receptors by hormones may involve the pituitary, it was relevant to reevaluate the effects of Hypox in male and female rats. Behaviorally, dopaminergic agonists exerted enhanced activity in Hypox male and female rats. It has been suggested that these changes are due to altered metabolism since no increase in the DA receptor populations was observed. Dopaminergic antagonists showed equivalent behavioral actions in male and female rats, whether intact or Hypox. Biochemically, neither the density nor the affinity of the striatal DA receptors is altered by Hypox in female rats for 1-2 weeks or male rats for 5-6 weeks. However, in female rats at 5-6 weeks after Hypox there is a significant decrease in receptor number. This decrease in density is not reflected in behavioral changes to either DA receptor agonists or antagonists. Therefore, all dopaminergic behavioral changes do not result from alterations in DA receptors and changes in DA receptors do not necessarily dictate altered behavioral responses to dopaminergic agents.


p53 regulates skeletal muscle mitophagy and mitochondrial quality control following denervation-induced muscle disuse.
Persistent inactivity promotes skeletal muscle atrophy, marked by mitochondrial aberrations that affect strength, mobility, and metabolic health leading to the advancement of disease. Mitochondrial quality control (MQC) pathways include biogenesis (synthesis), mitophagy/lysosomal turnover, and the mitochondrial unfolded protein response, which serve to maintain an optimal organelle network. Tumor suppressor p53 has been implicated in regulating muscle mitochondria in response to cellular stress; however, its role in the context of muscle disuse has yet to be explored, and whether p53 is necessary for MQC remains unclear. To address this, we subjected p53 muscle-specific KO (mKO) and WT mice to unilateral denervation. Transcriptomic and pathway analyses revealed dysregulation of pathways pertaining to mitochondrial function, and especially turnover, in mKO muscle following denervation. Protein and mRNA data of the MQC pathways indicated activation of the mitochondrial unfolded protein response and mitophagy-lysosome systems along with reductions in mitochondrial biogenesis and content in WT and mKO tissue following chronic denervation. However, p53 ablation also attenuated the expression of autophagy-mitophagy machinery, reduced autophagic flux, and enhanced lysosomal dysfunction. While similar reductions in mitochondrial biogenesis and content were observed between genotypes, MQC dysregulation exacerbated mitochondrial dysfunction in mKO fibers, evidenced by elevated reactive oxygen species. Moreover, acute experiments indicate that p53 mediates the expression of transcriptional regulators of MQC pathways as early as 1 day following denervation. Together, our data illustrate exacerbated mitochondrial dysregulation with denervation stress in p53 mKO tissue, thus indicating that p53 contributes to organellar maintenance via regulation of MQC pathways during muscle atrophy.


Abdominal wall endometrioma; a 10-year experience and brief review of the literature.
Abdominal wall endometrioma is a rare condition, which usually develops in a surgical scar of Cesarean section or hysterectomy. Certain factors relating to knowledge of the clinical pattern of this disease make correct diagnosis and treatment difficult. The aim was to identify the different forms of presentation of this disease entity through publishing the results from our experience of surgical management of such lesions. Patients diagnosed with abdominal wall endometrioma over a period of 10 y were identified from the comprehensive surgical database of our institution. The age, parity, symptoms, previous surgeries, initial diagnosis, diagnostic modalities, current operation, and recurrences were surveyed and analyzed. There were 40 patients with a mean age of 32.3 ± 5.2 y. All of the patients (100%, n = 40) had an abdominal mass in or adjacent to surgical scars. The main symptom was pain, noncyclic (45%, n =18), or cyclic (40%, n = 16) in nature. The mean duration of symptoms was 18.2 ± 23.4 mo. The preoperative diagnosis was correct in 47.5% (n = 19) of the cases. Surgical treatment failed in 3 cases (3/33, 9.1%), and the operations were performed once again. Abdominal wall endometriosis may be difficult to diagnose as it is comparatively an unfamiliar entity that has not received its due attention among general surgeons, so far. Therefore, in patients with a palpable subcutaneous mass in or around surgical scars with a history of violation of uterus, a thorough history and physical examination is necessary, and usually sufficient to make correct diagnosis of endometrioma.


Three-Dimensional Printing Role in Neurologic Disease.
Three-dimensional printing has evolved dramatically in recent years and is now available for clinical use. Technical operations of 2 of the most common rapid prototyping processes (stereolithography and fused deposition modeling) and the steps involved in the creation of a prototype are discussed. Current applications in human neurosurgery including presurgical planning and educational opportunities are reviewed before focusing on the current applications in veterinary neurology.


A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions.
A shifted balance between T helper 1 (Th1)-type and Th2-type cytokines has been hypothesised in cervical dysplasia. To evaluate possible deregulation of the cytokine network by estimating the expression of peripheral cytokines in different stages of cervical disease and in relation to the presence or absence of high risk human papillomavirus (HR-HPV). Twenty one HR-HPV positive women with high grade cervical intraepithelial neoplasia (CIN II-III) and 12 patients with invasive cervical carcinoma formed the study groups. Two control groups consisted of 10 HR-HPV positive and 11 HR-HPV negative women without CIN. Differences in leucocyte subgroups were evaluated by a differential leucocyte count. Plasma concentrations of tumour necrosis factor alpha (TNFalpha), TNFalpha receptors TNFRI and TNFRII, interferon gamma (IFNgamma), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were determined by enzyme linked immunosorbent assays. Leucocyte counts in patients with CIN III and carcinoma were significantly higher than in controls. Plasma IFNgamma concentrations were significantly lower in patients with CIN III and carcinoma than in women with CIN II or controls. Plasma concentrations of IL-12, IL-2, IL-4, and TNFalpha did not differ significantly between groups, but significantly lower plasma concentrations of TNFRII were found in CIN III and carcinoma compared with CIN II. IL-10 was detected with increased frequency in the plasma of patients with CIN III and carcinoma. These results indicate that a shift to a Th2-type cytokine pattern during the carcinogenesis of cervical cancer occurs in women with CIN III lesions.


Experimental studies on the nature of bonding of DNA*bipyridyl-(ethylenediamine)platinum(II) and DNA*netropsin complexes in solution and oriented wet-spun films.
The stability of complexes of NaDNA with bipyridyl- (ethylenediamine)platinum(II) (abbreviated [(bipy)Pt(en)](2+)) and with netropsin has been studied using two techniques: (i) ultraviolet (UV) melting experiments were done on NaDNA* [(bipy)Pt(en)](2+), showing that the [(bipy)Pt(en)](2+) ligand stabilizes the DNA double helix structure; and (ii) swelling measurements (via optical microscopy) as a function of relative humidity were done on wet-spun oriented films of NaDNA*[(bipy)Pt(en)](2+) and of NaDNA*netropsin. The swelling data shows that an irreversible transition of the films occurs at high relative humidity, first for the NaDNA*netropsin, then for pure NaDNA, and lastly for the NaDNA*[(bipy)Pt(en)](2+). These results are indicative that the [(bipy)Pt(en)](2+) complex stabilizes the intermolecular bonds which mediate the film swelling characteristics. A model is suggested for the binding of [(bipy)Pt(en)](2+) to DNA to explain why the swelling experiments show this ligand as increasing the intermolecular bond strength between the DNA double helices, while netropsin decreases this degree of stabilization.


Mediators of anaphylaxis.
Mediators of anaphylaxis, the most serious and best studied of the antihomeostatic reactions, are reviewed. Diseases in which these mediators may play autotoxic roles are briefly discussed.


Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders.
Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders.


CASE, the computer-automated structure evaluation method, correctly predicts the low mutagenicity for Salmonella of nitrated cyclopenta-fused polycyclic aromatic hydrocarbons.
Recently Goldring et al. [Mutation Res., 187 (1987) 67-77] reported the synthesis and purification of a series of nitro-substituted cyclopenta-fused polycyclic aromatic hydrocarbons. On the basis of expected charge distributions, these chemicals were predicted to be potent mutagens and, yet, contrary to expectation, they were found to be only weakly mutagenic for Salmonella. In their discussion, the authors suggest that application of CASE, an artificial intelligence system recently developed in these laboratories, would also not predict the low mutagenicity of this group of chemicals. In the present report, it is shown that CASE, in fact, correctly predicts the low mutagenicity of nitro-substituted cyclopenta-fused polycyclic aromatic hydrocarbons.


Determination of urinary estriol by radioimmunoassay. Modification of a commercial kit for serum analyses.
A simple and rapid method for urinary estriol determination is described. Modification of a commercially available kit for serum estriol gives a method for urinary estriol determination with a capacity of approximately 75 determinations a day. A high degree of accurary was revealed by indirect comparison with a mass fragmentographic method.


Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats.
Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS-associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. © 2015 Wiley Periodicals, Inc.


A week seems to be weak: tailoring duration of antibiotic treatment in Gram-negative ventilator-associated pneumonia.
The optimal length of antimicrobial therapy has not been extensively studied for a great majority of infections and, in critically ill patients affected by ventilator-associated pneumonia, is a persisting and unsolved issue confronting clinicians. The integration of biomarkers, clinical judgment, and microbiologic eradication might help to define a shorter duration for some ventilator-associated pneumonia episodes due to non-fermenting Gram-negative bacilli, but until these strategies are implemented in clinical practice for individualizing antibiotic treatment, a short-course duration does not seem to tailor a long benefit.


#Menopause: Examining the frequency of communications about menopause on twitter between 2014 and 2022.
This study explored the use of Twitter to communicate about menopause. Tweets in English posted between January 2014 and December 2022 with the hashtag "menopause" were extracted. Total global tweets and those from the UK, USA, Australia and Canada were examined. Globally, there were 314,974 tweets about menopause over this period, with an annual average of 34,997. There were notable differences between countries, with a large increase in use in the UK in 2018 and 2019, a reducing trend in use in the USA with a smaller increase in 2018 and 2019, and low stable usage in Australia and Canada.


A low-grade chondrosarcoma presenting as an unusual cervical mass in the hyoid bone: a case report.
A chondrosarcoma originating from the hyoid bone is very rare. Here, we describe a case of low-grade chondrosarcoma of hyoid origin and discuss its preoperative imaging features, including those on positron emission tomography-computed tomography, and its recurrence rate. A 42-year-old Japanese man noticed a mass in the right submandibular region of his neck. A hard 3.0 × 2.8 cm tumor was noted on the right side of his hyoid bone. The mass was immobile and moved with deglutition. Even though radiographic studies, including positron emission tomography-computed tomography, were inconclusive, the cartilaginous tumor was surgically removed en bloc, and the tumor was diagnosed based on the results of pathological investigations. Close follow-up is recommended in such cases due to the potential for recurrences, because local recurrence occurred in 50% of the reported cases of grade one chondrosarcomas.


Tricationic pyridium porphyrins appending different peripheral substituents: experimental and DFT studies on their interactions with DNA.
Four tricationic pyridium porphyrins appending hydroxyphenyl, methoxyphenyl, propionoxyphenyl or carboxyphenyl group at meso-20-position of porphyrin core have been synthesized and their abilities to bind and cleave DNA have been investigated. Using a combination of absorption, fluorescence, circular dichroism (CD) spectra, thermal DNA denaturation as well as viscosity measurements, their binding modes and intrinsic binding constants (K(b)) to calf DNA (CT DNA) were comparatively studied and also compared with those of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). The results suggest that the K(b) values of these porphyrins are greatly influenced by the number of positive charges and steric hindrance. Theoretical calculations applying the density functional theory (DFT) have been carried out and explain their DNA-binding properties reasonably. The efficiency of DNA photocleavage by these porphyrins shows high dependence on the values of K(b).


[Diagnosis of infection in surgery of the locomotor system with Tc-99m-HMPAO leukocyte scintigraphy].
70 patients with confirmed (23 patients) or suspected (47 patients) bacterial infection in the skeleton following diseases, injuries or operations in orthopedic surgery were investigated using Tc-99m-HMPAO leucocyte scintigraphy in order to evaluate the accuracy of this procedure. Infections could be detected correctly in 37 of 70 patients (right positives) while 28 patients had negative scans corresponding to the clinical course (right negatives). One false negative finding was observed. Five patients with clinically suspected infection had a focal uptake in the WBC-scan and were not operated subsequently. They range as false positive results, although they belong to a special group (Infection: Yes-Operation: No [IYON]-group). In the assessment of the Tc-99m-HMPAO-WBC-scan there was a senstivity of 97.1%, specificity of 82.9% and an overall accuracy of 90%. The method is suitable for detection of early and late infection as well as chronic or hematogenous osteomyelitis in the locomotor system. This means an important contribution in diagnosis of infection determining further operative or conservative treatment.


Exhaustion of arm fibrinolytic potential after repeated venous occlusions and local exercise.
The effect of repeated venous occlusions of the arm combined with local exercise was assessed in 10 healthy volunteers. The blood was drawn before and after three venous occlusions of 20 minutes. Between occlusions I - II, and II - III, twelve occlusions of 10 minutes were performed on the same arm while a small rubber ball was compressed 30 times per minute. Plasminogen activator (PA) activity was measured on plasminogen rich fibrin plates and by the euglobulin clot lysis time. A high increase in PA activity after venous occlusion (fibrinolytic potential) was present in all three occlusions on the first day, but fell to a very low level on the fourth day. The restitution of potential followed, but was not complete even on fifteenth day. These results indicate that PA continues to be released even after the termination of stimulation and can be temporarily depleted some days afterwards. An increase of fibrin(ogen) degradation products together with a slight decrease of alpha-2-antiplasmin in postocclusion samples, but no change in fibrinogen concentration speak in favour of a small fibrin(ogen)olysis during venous occlusion.


Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method.
Aim of this work is to prepare poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by dialysis method without surfactant and to investigate drug loading capacity and drug release. The size of PLGA nanoparticles was 269.9 +/- 118.7 nm in intensity average and the morphology of PLGA nanoparticles was spherical shape from the observation of SEM and TEM. In the effect of drug loading contents on the particle size distribution, PLGA nanoparticles were monomodal pattern with narrow size distribution in the empty and lower drug loading nanoparticles whereas bi- or trimodal pattern was showed in the higher drug loading ones. Release of clonazepam from PLGA nanoparticles with higher drug loading contents was slower than that with lower loading contents.


Are there gap junctions without connexins or pannexins?
Gap junctions (GJ) are one of the most common forms of intercellular communication. GJs are assembled from proteins that form channels connecting the cytoplasm of adjacent cells. They are considered to be the main or the only type of intercellular channels and the universal feature of all multicellular animals. Two unrelated protein families are currently considered to be involved in this function, namely, connexins and pannexins (pannexins/innexins). Pannexins were hypothesized to be the universal GJ proteins of multicellular animals, distinct from connexins that are characteristic of chordates only. Here we have revised this supposition by applying growing high throughput sequencing data from diverse metazoan species. Pannexins were found in Chordates, Ctenophores, Cnidarians, and in the most major groups of bilateral protostomes. Yet some metazoans appear to have neither connexins nor pannexins in their genomes. We detected no connexins or pannexins/innexins homologues in representatives of all five classes of echinoderms and their closest relatives hemichordates with available genomic sequences. Despite this, our intracellular recordings demonstrate direct electrical coupling between blastomeres at the 2-cell embryo of the echinoderm (starfish Asterias rubens). In these experiments, carboxyfluorescein fluorescent dye did not diffuse between electrically coupled cells. This excludes the possibility that the observed electrical coupling is mediated by incomplete cytoplasm separation during cleavage. Functional GJs are present in representatives of the clade that lack currently recognized GJ protein families. New undiscovered protein families utilized for intercellular channels are predicted. It is possible that the new type(s) of intercellular channels are present in parallel to pannexin and connexin gap junctions in animal groups, other than Echinodermata.


The association between primary language and quality of recovery following caesarean section: a prospective observational study.
New Zealand has a diverse population, one quarter classifying themselves as migrants. This study aimed to test the hypothesis that women whose primary language is not English report poorer recovery scores following caesarean section than primary English speakers. We recruited women to complete the ObsQoR-11 questionnaire 24 h after caesarean section. The questionnaire had been translated into the six most common languages spoken in our hospital. We categorised women into groups by primary language (English or non-English) and compared the ObsQoR-11 score between groups. Fifty-nine surveys were analysed. Groups did not differ for urgency of surgery, anaesthetic technique or postoperative analgesia. Similar scores were achieved in domains assessing surgical and anaesthetic sequelae, whereas questions about function and ability to care for the baby were scored lower by those whose primary language was not English. The Obs-QoR-11 score was significantly higher in English primary language speakers compared with non-English primary language speakers (mean 81.2, SD 17.7 vs 64.1, SD 20.9, P=0.001; 95% CI of the difference 7.1 to 27.2). Subgroup analysis of the non-English primary language speakers (n=26) showed a mean (SD) of 68.6 (16.9) in those who were fluent in English and 64.1 (26.5) in those who were not (P=0.099, 95% CI of the difference -2.9 to 32.4). Quality of recovery following caesarean section is poorer in those whose primary language is not English. Further research is needed to elucidate whether this is due to language barriers or other factors.


Analysis of possible carcinogenic compounds in recycled plastic modified asphalt.
The incorporation of recycled plastics in asphalt mixtures is getting a growing interest, however, exposing recycled plastics to the high working temperatures of asphalt has posed health and safety concerns. Few studies have paid attention to assessing health and environmental risks concerning recycled plastic-modified asphalt. This study investigates the release of 6 carcinogenic compounds from asphalt modified with recycled plastics, 4 volatile organic compounds (VOCs) and 2 polycyclic aromatic hydrocarbons (PAHs). The concentration of each compound was quantified by GC-MS. Human health risk assessments were conducted using probabilistic methods to assess the risk for an average Australian construction worker to get non-carcinogenic and carcinogenic health issues when exposed to conventional and plastic-modified asphalt fumes. Results showed that non-carcinogenic and carcinogenic risks related to VOC carcinogens (benzene, trichloroethylene, tetrachloroethylene and styrene) are negligible while PAHs (benzo[a]pyrene and dibenz[a,h]anthracene) constitute a possible non-carcinogenic risk and low carcinogenic risk for workers exposed to asphalt fumes. Overall the incorporation of recycled plastic in asphalt reduced the risk for workers to get non-carcinogenic and carcinogenic health issues compared to conventional asphalt mixes. ENVIRONMENTAL IMPLICATION: With increasing trends of using recycled plastics as road materials, concerns about the exposure of workers to carcinogenic gaseous emissions have been raised. This study demonstrates a non-carcinogenic and carcinogenic risk assessment on exposure to recycled plastic modified asphalt fumes. The findings suggest that recycled plastics decrease non-carcinogenic and carcinogenic risks compared to conventional asphalt.