Assembly of SPS/MgSi assisted by dopamine with excellent removal performance for ciprofloxacin.
In this work, magnesium silicate-based sulfonated polystyrene sphere composites (SPS/MgSi) were synthesized by one-step (SMD1) and two-step (SMD2) methods. For SMD1, MgSi particles were densely assembled on the surface of SPS, assisted by complexation between Fe3+ and hydroxyl phenol. For SMD2, SPS/SiO2 was firstly obtained by the same method as SMD1, and then SPS/SiO2 was transformed directly to SPS/MgSi under hydrothermal conditions. Therefore, MgSi obtained by the two-step method had an interwoven structure. Compared to SPS, MgSi and SMD1, SMD2 presented a larger specific surface area and more negative surface charges. Therefore, SMD2 showed superior adsorption performance toward CIP with concentrations of 5, 10 and 50 mg/L, and for 50 mg/L, the equilibrium adsorption capacity could reach 329.7 mg/g. The adsorption process is fast and can be described by the pseudo-second-order kinetic model. The relationship between pH value and Zeta potential demonstrated that electrostatic interaction dominated the adsorption process. In addition, competitive adsorption showed that the effect of Na+ was negligible but the effect of Ca2+ was dependent on its concentration. Humid acid (HA) could slightly promote the absorption of CIP by SMD2. After five rounds of adsorption-desorption, the equilibrium adsorption capacity of SMD2 still remained at 288.6 mg/L for 50 mg/L CIP. Notably, SMD2 presented likewise superior adsorption capacity for CIP with concentrations of 10 and 50 mg/L in Minjiang source water. All the results indicated that this synthesis method is universal and that SMD2 has potential as an adsorbent for CIP removal from aquatic environments.


Morphology of the cervical spinal cord on computed myelography.
To ensure adequate use of the technique of computed myelography (CM) it is necessary to have an exact picture of the morphology of the normal spinal cord as demonstrated by this technique. This has been obtained by studying the morphology and measuring the frontal and sagittal diameter of the cervical cord in 20 patients. The normal values are presented. The changes of this morphology in one patient with a tumour, one patient with atrophy of the spinal cord and in some patients with congenital malformations are also reported.


[Spontaneous rupture of uterus during delivery. Interpretation of cardiotocogram (author's transl)].
The authors report a case of silent rupture of uterus during delivery. The whole delivery was monitored by intrauterine pressure recording and fetal scalp electrode. Severe fetal bradycardia induced cesarian section. The retrospectively study of the papercover of fetal monitoring indicates the rupture of uterus.


Excess risk of subsequent primary cancers among colorectal carcinoma survivors, 1975-2001.
Studies of persons with colorectal cancer have reported increased risk of subsequent primary cancers. Results have not been consistent, however, and there is little information about such risk in specific races and ethnic populations. Using 1975-2001 data from the Surveillance, Epidemiology, and End Results (SEER) Program, we assembled 262,600 index cases of colorectal carcinoma to assess the occurrence of subsequent primary cancers in 13 noncolonic sites. Observed (O) subsequent cancers were compared with those expected (E) based on age-/sex-/race-/year-/site-specific rates in the SEER population. The standardized incidence ratio (SIR) and the absolute excess risk (AER) represent 'O / E' and 'O - E,' respectively. Colorectal carcinoma patients had significantly elevated SIRs for small gut, stomach (males), kidney, and corpus uteri cancers, ranging from 1.13 for stomach cancer in males to 3.45 for small gut cancer in females. Elevated SIRs for additional sites were seen in certain population subgroups: pancreas and ovary in persons aged <50 years, and prostate in black males. The excess burden, as assessed by AER, was notable for prostate cancer in black males and for corpus uteri cancer in females aged <50 years (26.5 and 9.5 cancers per 10,000 person-years, respectively), and it persisted beyond 5 years of follow-up. Although significantly elevated SIRs were found for several cancers, the excess burden was notable only for cancer of the prostate in black males and of the corpus uteri in females under age 50.


Transforming growth factor-ßs as modulators of pericellular proteolytic events.
Since the discovery of transforming growth factor-ß:s an increasing number of different biological effects have been attributed to this group of proteins. Analysis of the cellular responses to TGFß stimulation at the molecular level has indicated that TGFß acts as an activator of transcription of several genes. This may in part explain the plethora of various functions that have been ascribed to TGFß. In addition to the TGFß family of polypeptides there is an increasing number of related factors, whose major roles appear to be involved in developmental processes. A distinct feature of TGFß is its ability to regulate pericellular proteolysis of cultured cells. As yet this property has not been associated with other members of this group of polypeptides. Depending on the target cell type TGFß may either increase or decrease pericellular proteolytic activity. Proteolytic activation of latent TGFß and its possible inhibition by TGFß-induced protease inhibitors could be a physiological feed-back mechanism in the control of proteolytic activity in the vicinity of cells.


The effects of in vitro lipid peroxidation on the activity of rat liver microsomal glutathione S-transferase from rats supplemented or deficient in antioxidants.
Glutathione S-transferases are a group of multifunctional isozymes that play a central role in the detoxification of hydrophobic xenobiotics with electrophilic centers (1). In this study we investigated the effects of in vitro lipid peroxidation on the activity of liver microsomal glutathione S-transferases from rats either supplemented or deficient in both vitamin E and selenium. Increased formation of malondialdehyde (MDA), a by-product of lipid peroxidation, was associated with a decreased activity of rat liver microsomal glutathione S-transferase. The inhibition of glutathione S-transferase occurred rapidly in microsomes from rats fed a diet deficient in both vitamin E and selenium (the B diet) but was delayed for 15 minutes in microsomes from rats fed the same diet but supplemented with these micro-nutrients (B+E+Se diet). Lipid peroxidation inhibits microsomal glutathione S-transferase and this inhibition is modulated by dietary antioxidants.


New features of the IC(4) code and comparison of internal conversion coefficient calculations.
The IC(4) software developed to compare calculated internal conversion coefficients (ICC) has been enhanced by adding new features through the use of Borland Delphi and TeeChart. Particularly, the 3D-graph option enhances the possibilities of analyzing calculated ICC values. For example, the comparison between the results given by three sets of theoretical ICC tables for any arbitrary pair of calculated ICC can be presented in a much clearer manner. Their differences can be displayed as energy vs. atomic number surfaces. Results from the analyses of K-shell and total ICCs for E2, E3, M2, M3, and M4 multipolarity are discussed.


P2X7 receptor-mediated release of microglial prostanoids and miRNAs correlates with reversal of neuropathic hypersensitivity in rats.
P2X7 receptor antagonists have potential for treating various central nervous system (CNS) diseases, including neuropathic pain, although none have been approved for clinical use. Reasons may include insufficient understanding of P2X7 receptor signalling in pain, and the lack of a corresponding preclinical mechanistic biomarker. Lu AF27139 is a highly selective and potent small molecule antagonist at rat, mouse and human forms of the P2X7 receptor, with excellent pharmacokinetic and CNS permeability properties. In the current experiments, we probed the utility of previously characterized and novel signalling cascades exposed to Lu AF27139 using cultured microglia combined with release assays. Subsequently, we assessed the biomarker potential of identified candidate molecules in the rat chronic constriction injury (CCI) model of neuropathic pain; study design limitations precluded their assessment in spared nerve injury (SNI) rats. Lu AF27139 blocked several pain-relevant pathways downstream of P2X7 receptors in vitro. At brain and spinal cord receptor occupancy levels capable of functionally blocking P2X7 receptors, it diminished neuropathic hypersensitivity in SNI rats, and less potently in CCI rats. Although tissue levels of numerous molecules previously linked to neuropathic pain and P2X7 receptor function (e.g. IL-6, IL-1β, cathepsin-S, 2-AG) were unaffected by CCI, Lu AF27139-mediated regulation of spinal PGE2 and miRNA (e.g. rno-miR-93-5p) levels increased by CCI aligned with its ability to diminish neuropathic hypersensitivity. We have identified a pain-relevant P2X7 receptor-regulated mechanism in neuropathic rats, which could hold promise as a translatable biomarker and by association enhance the clinical progression of P2X7 receptor antagonists in neuropathic pain. Sub-optimal translation of preclinical molecules has hindered the clinical development of novel mechanism of action analgesics. We have undertaken a comprehensive in vitro analysis of migroglial signalling mechanisms recruited upon P2X7 receptor activation, a number of which were shown to be modulated by a selective P2X7 receptor antagonist in a well characterized animal model of neuropathic pain. Subject to further confirmation in other neuropathic models, this opens up the possibility to investigate their clinical utility as potential pain biomarkers in patients.


Serological Response to Vaccination after Autologous Transplantation for Multiple Myeloma Is Associated with Improved Progression-Free and Overall Survival.
Revaccination after autologous hematopoietic cell transplantation (AHCT) is recommended in post-HCT survivorship guidelines to restore humoral immunity. Data on seroconversion after AHCT and vaccination in multiple myeloma (MM) patients are limited. We investigated the feasibility and effectiveness of vaccination post-AHCT and analyzed the restoration of humoral immunity and patient prognosis. Anti-pathogen titers were measured within a median of 2 days before and 96 days after AHCT and following revaccination in 139 MM patients who had a first AHCT from 2013 to 2016. Most (84%) patients received at least one dose of any planned vaccines. High-dose melphalan with AHCT restored measurable immunity in 18% of patients. In an additional >60% of patients, seroconversion occurred after vaccination; however, despite vaccination, 20% of patients remained seronegative for most pathogens. Attainment of MM complete response post-AHCT was associated with higher rates of seroconversion which yielded significantly longer progression-free and overall survival. Our study demonstrates the feasibility of post-AHCT vaccination, supporting measurement of post-vaccination titers to determine which patients should be considered for antimicrobial prophylaxis, as seroconversion does not occur in all patients. Titer seroconversion is a potential indicator of the immunological effects of AHCT, with restoration of humoral immunity demonstrating improved survival.


Design, Synthesis, and Properties of Phosphoramidate 2',5'-Linked Branched RNA: Toward the Rational Design of Inhibitors of the RNA Lariat Debranching Enzyme.
Two RNA fragments linked by means of a 2',5' phosphodiester bridge (2' hydroxyl of one fragment connected to the 5' hydroxyl of the other) constitute a class of nucleic acids known as 2'-5' branched RNAs (bRNAs). In this report we show that bRNA analogues containing 2'-5' phosphoramidate linkages (bN-RNAs) inhibit the lariat debranching enzyme, a 2',5'-phosphodiesterase that has recently been implicated in neurodegenerative diseases associated with aging. bN-RNAs were efficiently generated using automated solid-phase synthesis and suitably protected branchpoint building blocks. Two orthogonally removable groups, namely the 4-monomethoxytrityl (MMTr) group and the fluorenylmethyl-oxycarbonyl (Fmoc) groups, were evaluated as protecting groups of the 2' amino functionality. The 2'-N-Fmoc methodology was found to successfully produce bN-RNAs on solid-phase oligonucleotide synthesis. The synthesized bN-RNAs resisted hydrolysis by the lariat debranching enzyme (Dbr1) and, in addition, were shown to attenuate the Dbr1-mediated hydrolysis of native bRNA.


Assessing cost-effectiveness of hepatitis C testing pathways in Georgia using the Hep C Testing Calculator.
The cost of testing can be a substantial contributor to hepatitis C virus (HCV) elimination program costs in many low- and middle-income countries such as Georgia, resulting in the need for innovative and cost-effective strategies for testing. Our objective was to investigate the most cost-effective testing pathways for scaling-up HCV testing in Georgia. We developed a Markov-based model with a lifetime horizon that simulates the natural history of HCV, and the cost of detection and treatment of HCV. We then created an interactive online tool that uses results from the Markov-based model to evaluate the cost-effectiveness of different HCV testing pathways. We compared the current standard-of-care (SoC) testing pathway and four innovative testing pathways for Georgia. The SoC testing was cost-saving compared to no testing, but all four new HCV testing pathways further increased QALYs and decreased costs. The pathway with the highest patient follow-up, due to on-site testing, resulted in the highest discounted QALYs (123 QALY more than the SoC) and lowest costs ($127,052 less than the SoC) per 10,000 persons screened. The current testing algorithm in Georgia can be replaced with a new pathway that is more effective while being cost-saving.


A radioisotopic technique for measuring the mononuclear inflammatory response in Sindbis virus-induced encephalitis of mice.
The mononuclear inflammation occurring in Sindbis virus-induced encephalitis of mice has been measured by means of pulse labelling with [125I]UdR at a defined time after infection. The method should be applicable to other studies of encephalitis and of mononuclear cellular infiltration occurring in other organs as a result of disease or infection.


Risk factors for pre-eclampsia in Lagos, Nigeria.
Pre-eclampsia is an important cause of maternal mortality. Although there have been many studies worldwide on pre-eclampsia, not many have come from black Africa. A case-control study was conducted in a tertiary hospital in Nigeria (the black African nation with the highest population) between February 2001 and August 2002 to determine the risk factors for eclampsia. Information on socio-demographic characteristics, pre-pregnancy weight, medical history and previous obstetric history, and level of stress at home and at work was obtained by face-to-face interviews. Multiple logistic regression analysis was used to determine the risk factors for pre-eclampsia. One hundred and thirty seven (7.6%) of the 1803 women who delivered during the period had pre-eclampsia/eclampsia. Of these, 128 (93.4%) were analysed. Ninety-one (71.1%) women were primigravidae. Age < or = 19 years was not considered a risk factor. The risk factors that were associated with increased risk of pre-eclampsia were: nulliparity (OR 4.77; 95% CI 2.90-7.78), stressful work during pregnancy (OR 2.10; 95% CI 1.20-3.71), stressful home environment (OR 1.97; 95% CI 1.27-3.69), previous pre-eclampsia (OR 11.68; CI 3.81-37.61), history of chronic hypertension (OR 2.21; 95% CI 1.17-6.20), a body weight greater than 80 kg (OR 2.01; 95% CI 1.05-3.87); and multiple pregnancy (OR 2.71; 95% CI 1.27-6.13). Risk factors for pre-eclampsia among Nigerian women are not different from those that have been reported in other studies. Weight reduction, good control of chronic hypertension, and reduction of stressful conditions at home and in pregnancy could be steps towards the primary prevention of this disorder.


Report of Haemophilus Influenzae serotype a intracranial infections in older children.
Haemophilus influenzae (Hi) is subdivided into typeable (a-f) and non-typeable groups. Hi serotype b (Hib) has historically been one of the important pathogens responsible for invasive infection. However, after widespread Hib vaccination, the emergence of other Hi serotypes, specifically Hi serotype a (Hia), was noted during the last few decades, mostly in children younger than 5 years of age. We present two cases of severe intracranial infections with detected Hia in patients > 5 years of age within a short time frame and within the same geographic area. Epidemiological studies and surveillance on Hia-related illnesses in all age groups worldwide are needed to better understand the clinical and epidemiological characteristics of Hia. This can establish a platform to develop a candidate vaccine against Hia that might protect children of all ages.


The utility of transbronchial rebiopsy for peripheral pulmonary lesions in patients with advanced non-squamous non-small cell lung cancer.
Patients treated for non-squamous (non-Sq) non-small cell lung cancer (NSCLC) often require repeat biopsies to determine the optimal subsequent treatment. However, the differences between rebiopsy and initial biopsy in terms of their diagnostic yields and their ability to test the molecular profiles using bronchoscopy with radial endobronchial ultrasound guidance in patients with advanced NSCLC remain unclear. Hence, we aimed to compare the diagnostic yields and ability for molecular analyses of rebiopsies with those of initial biopsies. We investigated 301 patients with advanced non-Sq NSCLC who underwent radial endobronchial ultrasound-guided transbronchial biopsy (TBB) for peripheral pulmonary lesions (PPLs) between August 2014 and July 2017. Patients were divided into the rebiopsy and initial biopsy groups: the latter referred to the biopsy that determined the definitive diagnosis. The diagnostic yields and ability for molecular analyses were compared between the two groups, and the factors affecting the TBB diagnostic yield were identified using univariate and multivariate analyses. The diagnostic yields of the rebiopsy and initial biopsy groups were comparable (86.8 and 90.8%, respectively; p = 0.287). Furthermore, 93.0 and 94.0% of the patients in the rebiopsy and initial biopsy groups, respectively, had adequate specimens for gene profiling and mutational analysis (p = 0.765). The factors that increased the diagnostic yield were a positive bronchus sign (p < 0.001) and tumour location within the internal two-thirds of the lungs (p = 0.026). The PPL diagnostic yield of the rebiopsy group was as high as that of the initial biopsy group. Hence, TBB for PPLs is feasible for patients requiring rebiopsy as well as for those with initial diagnoses. Adequate, high-quality biopsy specimens can be obtained by transbronchial rebiopsy for molecular testing.


[Taking into consideration patient concerns for the elaboration of educational programs for chronic renal failure patients].
The objective was to take into consideration patient concerns for an original qualitative approach to the elaboration of three therapeutic education programs (TEP) designed for chronic renal failure patients, transplantation recipients, and dialysis patients. Four discussion groups involved patients with non-terminal chronic renal failure (one group), transplantation recipients (one group), and dialysis patients (two groups). Topics discussed were patients' knowledge of the TEP and their disease and treatment, patients' expectations concerning the educative content and the organisation of the TEP. For all levels of chronic renal failure, patient expectations focused on nutrition, treatments, and the social and occupational supportive network. Patients with non-terminal renal failure also expressed their expectations concerning the comprehension of laboratory tests and the course of their renal disease. Transplantation recipients wanted to strengthen their knowledge about graft evolution and immunosuppression. Dialysis patients expressed their concerns about disease announcement and the decision for dialysis. While certain topics were common, patients were preoccupied by different problems depending on their degree of renal insufficiency. Nephrolor thus integrated these different levels of concern into the elaboration of E'Dire programs designed for non-terminal renal failure patients and EDUGREFFE for transplant recipients. The third program designed for dialysis patients is currently in the development phase.


Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies.
The role of quantitative proton magnetic resonance imaging (MRI) for the evaluation of immunopathological lesions in the CNS was studied in adoptively transferred experimental allergic encephalomyelitis (AT-EAE). We utilized a recently established treatment model, inhibition of the cell adhesion molecule ICAM-1 by the monoclonal antibody 1A-29. The animals were scanned on days 3, 5 and 7 after injection of encephalitogenic T-cells, before and after bolus injection of Gd-DTPA by performing T1-measurements to assess the integrity of the blood-brain barrier (BBB). On day 7, immunohistochemistry was performed looking for T-cells, activated macrophages, and albumin staining. There was clinical evidence of partial inhibition of AT-EAE in rats treated with antibodies against ICAM-1. This finding was in line with a significantly reduced number of T-cells in the medulla. However, the number of activated macrophages and the distribution of albumin did not differ from untreated AT-EAE animals. The histological findings are in agreement with the MRI data before and after Gd-DTPA injection which were similar in treated and untreated AT-EAE rats on day 3 and 5. On day 7 after Gd-DTPA injection there was evidence of a delayed breakdown of the BBB in the treated rats. The observation of a dissociation of clinical and MRI findings, especially evidence of Gd-enhancement despite clinical improvement, may be important in the context of interpreting MRI studies in MS patients in treatment trials.


["Tension band"-osteosynthesis (author's transl)].
This report deals with the early results of the tension-band-osteosynthesis in 365 patients. With this simple method functional stability can be achieved even in fractures where the implanation of plates, screws and so on is impossible (near a joint, fractures of hand and foot, some fractures in children).


Otoscopic and audiological findings in different populations of 5-14 year-old schoolchildren in Colombia.
To present the otoscopic and audiological findings of studies carried out in groups of 5-14 year old schoolchildren in diverse indigenous, White, and African descended communities in the Republic of Colombia. The present study is descriptive and cross-sectional. We obtained a convenience sample for the analysis. We define acute otitis media (AOM), (bulging or redness); tympanic perforation (TP), (disruption of continuity in the tympanic membrane) and sequelea (scarring, myringosclerosis, retractions, secrections). Our results are described as frequencies in percentages. Audiometry was performed in every student. Readings were taken at 250, 500, 1000, 2000, 4000, and 8000 Hz for air-conduction and bone-conduction thresholds. Normal hearing is considered up to 20 dB, mild sensorineural hearing loss between 21 and 39 dB, moderate between 40 and 59 dB, severe between 60 and 89 dB and profound more than 90 dB. For conductive hearing loss the air-bone gap is measured. 3052 otoscopies were conducted in 1526 schoolchildren. Males predominated in each group except in the Wayuu group. Otoscopic abnormalities rates varied between 1.5% in Providencia group, up to 9.6% in the Amazon groups. No perforations were found in the Wayuu Indian schoolchildren and the highest frequency of Tympanic perforations (1.2%) and sequelaes (8.2)% in the Amazon groups. Audiometric findings were normal in 94-98% of cases. Conductive hearing loss (CHL) was found in 5.5% of Amazon groups and the lowest (1.4%) in the Wayuu groups. Slight to moderate Neurosensorial Hearing Loss (NHL) were found in 1.3% in the Arhuaca communities and moderate 0.9% in the Amazon groups. The present study is the first conducted in Colombia to evaluate the frequency of ear diseases and sequelae in populations of 5-14 year old children. High prevalences of sequelaes were found in the indigenous groups of the Amazon and the lowest in the Black schoolchildren on the island of Providencia. It is recommended that medical anthropological studies be conducted in these areas, and evaluation done on the probable connection between these types of diseases and processes of intercultural interaction.


Response of rat immature enterocytes to insulin: regulation by receptor binding and endoluminal polyamine uptake.
The mechanism(s) by which insulin stimulates enzyme expression in rat immature enterocytes are unknown. The purpose of this study was to investigate these mechanism(s). The effects of insulin or an antireceptor monoclonal antibody (RPN 538) were assessed on microvillous enzyme activities and the endoluminal uptake of [14C]spermine. Changes in de novo synthesis of polyamines were measured by mucosal ornithine decarboxylase activity. In sucklings (day 14), administration of insulin failed to induce intestinal ornithine decarboxylase activity, whereas in older rats (day 18 and 20), ornithine decarboxylase was enhanced by 2-2.5-fold. Immature enterocytes from sucklings, pretreated with alpha-difluoromethylornithine, remained sensitive to insulin and expressed enzyme activities at levels equal to controls. In response to insulin, the uptake of [14C]spermine and the mucosal concentrations of spermine and spermidine were increased by 30%, 13%, and 39%, respectively. Administration of RPN 538 had no effect on [14C]-spermine uptake, but it prevented the effects of endogenous insulin on enzyme expression. The enzymatic response of immature enterocytes to insulin is mediated by binding of the hormone to its receptor and is transduced into the cell without de novo synthesis of polyamines. The regulation by insulin of the endoluminal uptake of spermine could be critical for intestinal maturation.


Hormetic Effects of Early Juvenile Radiation Exposure on Adult Reproduction and Offspring Performance in the Cricket (Acheta domesticus).
Exposure to low-dose ionizing radiation can have positive impacts on biological performance-a concept known as hormesis. Although radiation hormesis is well-documented, the predominant focus has been medical. In comparison, little research has examined potential effects of early life radiation stress on organismal investment in life history traits that closely influence evolutionary fitness (eg, patterns of growth, survival, and reproduction). Evaluating the fitness consequences of radiation stress is important, given that low-level radiation pollution from anthropogenic sources is considered a major threat to natural ecosystems. Using the cricket (Acheta domesticus), we tested a wide range of doses to assess whether a single juvenile exposure to radiation could induce hormetic benefits on lifetime fitness measures. Consistent with hormesis, we found that low-dose juvenile radiation positively impacted female fecundity, offspring size, and offspring performance. Remarkably, even a single low dose of radiation in early juvenile development can elicit a range of positive fitness effects emerging over the life span and even into the next generation.


Effects of equisetin on rat liver mitochondria: evidence for inhibition of substrate anion carriers of the inner membrane.
The effect of equisetin, an antibiotic produced by Fusarium equiseti, has been studied on mitochondrial functions (respiration, ATPase, ion transport). Equisetin inhibits the DNP-stimulated ATPase activity of rat liver mitochondria and mitoplasts in a concentration-dependent manner; 50% inhibition is caused by about 8 nmol equisetin/mg protein. The antibiotic is without effect either on the ATPase activity of submitochondrial particles or on the purified F1-ATPase. It inhibits both the ADP- or DNP-activated oxygen uptake by mitochondria in the presence of glutamate+malate or succinate as substrates, but only the ADP-stimulated respiration is inhibited if the electron donors are TMPD+ascorbate. It does not affect the NADH or succinate oxidation of submitochondrial particles. Equisetin inhibits in a concentration-dependent manner the active Ca(2+)-uptake of mitochondria energized both by ATP or succinate without affecting the Ca(2+)-uniporter itself. The antibiotic inhibits the ATP-uptake by mitochondria (50% inhibition at about 8 nmol equisetin/mg protein) and the Pi and dicarboxylate carrier. It does not lower the membrane potential at least up to 200 nmol/mg protein concentration. The data presented in this paper indicate that equisetin specifically inhibits the substrate anion carriers of the mitochondrial inner membrane.


Metabiosis of proteolytic moulds and Salmonella in raw, ripe tomatoes.
The aim of this study was to determine the survival and growth characteristics of Salmonella enterica in sound and chill-injured tomatoes as influenced by co-infection with proteolytic moulds. Sound (not chill injured) raw, ripe tomatoes (Lycopersicon esculentum Mill. 'Roma') were inoculated with a five-serotype mixture of S. enterica and/or Alternata alternata (two strains), Cladosporium herbarum and C. cladosporioides. Simultaneous and delayed (3 days) inoculation of tomatoes with Salmonella and each mould was studied. Growth of moulds in sound tomatoes stored at 15 and 25 degrees C for up to 10 days was accompanied by increased pH of radial pericarp tissue (pulp), which enhanced the growth of Salmonella. Growth of moulds and Salmonella at 25 degrees C was enhanced in chill-injured tomatoes compared with sound tomatoes. Growth of proteolytic moulds in tomatoes stored at conditions simulating those commonly used in commercial postharvest storage and handling promotes the growth of Salmonella that may be an incidental contaminant. Discarding tomatoes that are infected by moulds is important in handling and minimal processing practices designed to minimize the risk of human salmonellosis.


Impact of shear stress and pH changes on floc size and removal of dissolved organic matter (DOM).
The impact of shear stress and increases in pH on the release of natural dissolved organic matter (DOM) from Fe-DOM and Al-DOM flocs was investigated for a high organic matter, low turbidity raw water by application of a dynamic extinction probe (DEP) and liquid chromatography organic carbon detection (LC-OCD). It was shown that high shear forces resulted in a breakage of Fe-DOM flocs. Re-growth took place during subsequent low shear phases. However, re-growth was limited. The flocs regained a size of about 50% of the size after initial coagulation. Cyclic shearing resulted in slower re-growth rates. A new insight was that when enough time was given, similar sizes of the re-grown flocs were regained. As shown by bulk DOC, only an insignificant release of DOM took place when flocs were exposed to shear. Increase in shear stress resulted in smaller flocs with higher specific outer surface area. However, DOM removal did not change. Thus, there was no increase in adsorption capacity due to floc breakage. Consequently, DOM must be adsorbed inside the amorphous flocs rather than on the outer surface. Also, as shear results in more compact flocs, compaction does not have an effect on DOM removal. A pH increase of 0.5, as it can happen during water treatment after coagulation, resulted in a release of DOM. Humic substances accounted for the largest proportion of total DOM released. The increase in pH did not affect floc size. Consequently, DOM removal is mainly governed by the dependence of DOM properties on pH with the final pH determining the degree of DOM removal and not the path on which this pH is reached. The physical properties of the flocs have no impact on DOM removal.


Developmental therapeutics program at the NCI: molecular target and drug discovery process.
As the drug discovery and developmental arm of the National Cancer Institute (NCI), the Developmental Therapeutics Program (DTP) plans, conducts and facilitates development of therapeutic agents for cancer and AIDS. DTP's goal is to turn 'molecules into medicine for the public health'. Areas of support by DTP are discovery, development and pathways to development for the intramural and the extramural community. The Developmental Therapeutics Program (DTP) operates a repository of synthetic and pure natural products, which are evaluated as potential anticancer agents. The repository derives from a historical database of greater than 600 000 compounds, which have been supplied to DTP from a variety of sources worldwide. The in vitro anti-cancer drug cell line screen established at DTP is unique in several respects. It has changed the NCI emphasis from a compound-oriented drug discovery effort to a disease-panel oriented exercise, emphasized human tumor cells derived from solid tumors, developed a high volume screening method that can adapt to processing of numerous chemical agents or natural source-derived extracts, that has minimized the use of animals, and saved on the amount of material required for the initial screening. The hollow fiber assay created at the DTP has demonstrated the ability to provide quantitative initial indices of in vivo drug efficacy, with minimum expenditures of time and materials and is currently being utilized as the initial in vivo experience for agents found to have reproducible activity in the in vitroanticancer drug screen. Drugs showing activity with unique mechanisms of actions are being further developed for treatment of hematopoietic neoplasms, prominent examples being flavopiridol, UCN-01 and depsipeptide among others.


Rapid evaluation of malaria parasite density and standardization of thick smear examination for epidemiological investigations.
The results of epidemiological surveys and the follow-up of malaria endemicity are often difficult to compare due to the high frequency of low-density parasitaemia in semi-immune populations. Detecting malaria parasites is dependent on the conditions and methods of parasitological examination. A standardized method of examination in epidemiological surveys is proposed: this includes the systematic rapid determination of parasite density.


Extracellular vesicles as a horizontal gene transfer mechanism in Leishmania.
Douanne et al. recently reported horizontal gene transfer (HGT) mediated by extracellular vesicles (EVs) in Leishmania; this constitutes the first report of this phenomenon in parasites. They showed that EVs facilitate the transmission of drug-resistance genes and increased cell fitness in stressful environments, indicating potential clinical application of these findings.


Correction to "New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance".
[This corrects the article DOI: 10.1021/acscentsci.3c00286.].


Dynamic splinting following flexor tendon repair.
Electromyographic investigation of subjects wearing dynamic flexor tendon repair (Kleinert) splints shows a wide variability in the amount of contraction in the flexor digitorum profundus muscle during extension of the finger. We suggest there is no advantage in giving extra resistance to the extensor muscles, and that the strength of the rubber bands needs to be only just sufficient to flex the finger passively back to its resting position.


[Paraplegia caused by vertebral compression fractures in senile osteoporosis].
Paraplegia followed spontaneous deformed osteoporotic spine is very rare. Our own 3 cases treated conservatively in two and operatively in one with success and 11 cases reported in the literatures were analyzed. All patients were recovered from paraplegia. One patient was died one and a half year after the recovery of her paralytic episode. Thorough autopsy study of this patient showed no organic lesion in the regarded spinal cord due to such kind of spine deformity.


Heating, ventilation, and air-conditioning systems in healthcare: a scoping review.
Guidelines for heating, ventilation, and air-conditioning systems have been developed for different settings. However, there is a lack of up-to-date evidence providing concrete recommendations for the heating, ventilation, and air-conditioning systems of an isolation room, which is essential to appropriately guide infection control policies. To highlight the guidelines for heating, ventilation, and air-conditioning systems in isolation rooms to inform relevant stakeholders and policymakers. A systematic search was performed based on Joanna Briggs Methodology using five databases (CINAHL, Embase, Joanna Briggs Institute, Medline, and Web of Science) and websites. Eight articles published by government departments were included in this review. Most studies recommended controlled airflow without recirculation, 12 air changes per hour, high-efficiency particulate air filtrate to exhaust contaminated air from the airborne isolation room, humidity ≤60%, and temperature in the range of 18-30 °C. This review provides further evidence that there is a need for interdisciplinary collaborative research to quantify the optimum range for heating, ventilation, and air conditioning system parameters, considering door types, anterooms, and bed management, to effectively reduce the transmission of infection in isolation rooms.


Quantification of Secondary Metabolites.
Plants are a rich source of secondary metabolites that have medicinal and aromatic properties. Secondary metabolites such as alkaloids, iridoids and phenolics generally produced by plants for their defence mechanisms have been implicated in the therapeutic properties of most medicinal plants. Hence, quantification of these metabolites will aid to discover new and effective drugs from plant sources and also to scientifically validate the existing traditional practices. Quantification of large group of phytochemicals such as phenolics and flavonoids is quantified in this context.


A critical assessment of sparse PCA (research): why (one should acknowledge that) weights are not loadings.
Principal component analysis (PCA) is an important tool for analyzing large collections of variables. It functions both as a pre-processing tool to summarize many variables into components and as a method to reveal structure in data. Different coefficients play a central role in these two uses. One focuses on the weights when the goal is summarization, while one inspects the loadings if the goal is to reveal structure. It is well known that the solutions to the two approaches can be found by singular value decomposition; weights, loadings, and right singular vectors are mathematically equivalent. What is often overlooked, is that they are no longer equivalent in the setting of sparse PCA methods which induce zeros either in the weights or the loadings. The lack of awareness for this difference has led to questionable research practices in sparse PCA. First, in simulation studies data is generated mostly based only on structures with sparse singular vectors or sparse loadings, neglecting the structure with sparse weights. Second, reported results represent local optima as the iterative routines are often initiated with the right singular vectors. In this paper we critically re-assess sparse PCA methods by also including data generating schemes characterized by sparse weights and different initialization strategies. The results show that relying on commonly used data generating models can lead to over-optimistic conclusions. They also highlight the impact of choice between sparse weights versus sparse loadings methods and the initialization strategies. The practical consequences of this choice are illustrated with empirical datasets.


Wellness for Warriors: Developing and Disseminating a Veteran-centric Wellness Guide.
Evidence-based self-help wellness interventions have several benefits, including low cost, brevity, and lack of need for a health care professional. Veterans, in particular, may benefit from a self-guided resource, given a culture of self-reliance, mental health help-seeking stigma, and a high need for mental health care. Despite the high need, few self-help resources are designed for veterans. The goal of this project was to create the Veteran Wellness Guide, a self-guided resource comprising SMART goal setting and evidence-based interventions for veterans (e.g., self-kindness, gratitude, diaphragmatic breathing, mindfulness). First, a Veteran Engagement Group reviewed the guide and provided feedback on veteran-centric content and design. After the authors revised the guide, a subset of the group approved changes. Additional veterans used it for 2 weeks and provided feedback. Veterans reported the guide as being highly useful, were willing to recommend it to other veterans, and identified a need for it in the veteran community. Veterans and Veterans Health Administration clinicians and leadership helped to craft a dissemination plan to reach veterans whether they receive care through the Veterans Health Administration or the community. Partnering with veterans in the creation of the wellness guide led to a veteran-centric product tailored to meet the unique wellness needs of veterans. The guide has been nationally disseminated and downloaded over 3000 times and can be downloaded for free from our website.


Morphometric similarity network alterations in COVID-19 survivors correlate with behavioral features and transcriptional signatures.
To explore the differences in the cortical morphometric similarity network (MSN) between COVID-19 survivors and healthy controls, and the correlation between these differences and behavioralfeatures and transcriptional signatures. 39 COVID-19 survivors and 39 age-, sex- and education years-matched healthy controls (HCs) were included. All participants underwent MRI and behavioral assessments (PCL-17, GAD-7, PHQ-9). MSN analysis was used to compute COVID-19 survivors vs. HCs differences across brain regions. Correlation analysis was used to determine the associations between regional MSN differences and behavioral assessments, and determine the spatial similarities between regional MSN differences and risk genes transcriptional activity. COVID-19 survivors exhibited decreased regional MSN in insula, precuneus, transverse temporal, entorhinal, para-hippocampal, rostral middle frontal and supramarginal cortices, and increased regional MSN in pars triangularis, lateral orbitofrontal, superior frontal, superior parietal, postcentral, and inferior temporal cortices. Regional MSN value of lateral orbitofrontal cortex was positively associated with GAD-7 and PHQ-9 scores, and rostral middle frontal was negatively related to PHQ-9 scores. The analysis of spatial similarities showed that seven risk genes (MFGE8, MOB2, NUP62, PMPCA, SDSL, TMEM178B, and ZBTB11) were related to regional MSN values. The MSN differences were associated with behavioral and transcriptional signatures, early psychological counseling or intervention may be required to COVID-19 survivors. Our study provided a new insight into understanding the altered coordination of structure in COVID-19 and may offer a new endophenotype to further investigate the brain substrate.


Right posterior brain-damaged patients are poor at assessing the age of a face.
The ability to order unknown faces by age was investigated in right and left brain-damaged patients, divided into posterior and non-posterior groups on the basis of CT scan findings. A face recognition test and a figure ground discrimination test were also given. All three tests were affected by brain damage, but their sensitivity to the locus and side of lesion varied. While no hemispheric difference was found on the figure ground discrimination test, the face age test significantly discriminated patients with right posterior injury from any other brain-damaged group. The face recognition test occupied an intermediate position, with right posterior patients significantly impaired in comparison with right non-posterior patients and marginally impaired with respect to left posterior patients. Aphasia did not affect the performance of left brain-damaged patients on any of the tests. The findings are interpreted as evidence that damage of the right posterior hemisphere areas disrupts the structural encoding of visual information. Four prosopagnosic patients were also tested. Only those showing signs of apperceptive agnosia failed on the face age test.


Prevalence of premature ovarian failure in systemic lupus erythematosus patients treated with immunosuppressive agents in Thailand.
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries. To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy. Women aged 18-40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L. Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95% CI 1.96-147.72, p = 0.01). From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients.


The availability of state-level data on interstate cattle movements in the United States.
Knowledge about the patterns of animal movement--particularly feeder-cattle movement--within the USA is necessary in order to anticipate how diseases might be spread geographically. This study was conducted to explore the availability of interstate-level movement data which might be used to develop a more coherent national picture of interstate feeder-cattle movement. State Statistical Offices of the National Agricultural Statistics Service, 1996 (NASS) and Departments of Agriculture in all 50 states were contacted to determine the type of information collected regarding the import and export of feeder cattle. Eighteen of the 50 states contacted recorded updated import and export information by using certificates of veterinary inspection and (occasionally) entry permits for verification. The 18 states were: Alabama, Colorado, Florida, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Maryland, Massachusetts, Minnesota, New Jersey, Pennsylvania, Texas, West Virginia, Wisconsin, and Wyoming. Profiles of import and export data from Kansas, Texas, Colorado and Iowa (the primary receivers of 51% of total 1995 imports) were developed. These four states received at least 50% of their cattle imports from < 9 different states. As a result, approximately half of the nation's import movement can be explained by a total of 13 states and Mexico (excluding duplicates). Also, > 50% of the exports from Kansas, Texas, Colorado, and Iowa go to < or = 3 states. This import and export information confirms conclusions of others that cattle tend to move toward the center of the USA. However, if more states kept comprehensive, up-to-date records of movement information, knowledge about cattle-movement patterns in the USA would be importantly increased. The lack of specific notations on certificates of veterinary inspection can lead only to perceived trends; the present records have limited value in tracking animal movement.


Impact of drug loading on the compaction properties of itraconazole-PVPVA amorphous solid dispersions.
The impact of drug loading on the compaction properties of itraconazole (ITZ)- poly(vinylpyrrolidone-co-vinyl-acetate) (PVPVA) amorphous solid dispersions (ASDs) was studied. Neat amorphous ITZ, amorphous PVPVA, and their ASDs from 20% to 80% ITZ loadings were prepared by spray drying. Physical characterization showed that all powders have comparable particle size and morphology. All samples were equilibrated under 33% RH prior to compaction studies using a compaction simulator. Tabletability and compactability profiles of the ASD powders differed significantly, while their compressibility was similar. At compaction pressures from 50 to 150 MPa, tensile strength of ASD compacts increased with the increase of ITZ loading, reaching to the maximum at 40-60% ITZ loadings and then decreased as ITZ loading further increased. However, at the compaction pressure of 200 MPa, a monotonic decrease of tensile strength with the increase of ITZ loading was observed. In addition, except for the ASD with 20% ITZ loading, the detrimental effect of compaction pressure on tensile strength was observed at pressures at or above 150 MPa. Overall, this work highlights the importance of evaluating the compaction properties of ASD intermediates prior to downstream tablet development, especially if a high drug loading ASD is desired.


Adaptation of a microbial community to demand-oriented biological methanation.
Biological conversion of the surplus of renewable electricity and carbon dioxide (CO2) from biogas plants to biomethane (CH4) could support energy storage and strengthen the power grid. Biological methanation (BM) is linked closely to the activity of biogas-producing Bacteria and methanogenic Archaea. During reactor operations, the microbiome is often subject to various changes, e.g., substrate limitation or pH-shifts, whereby the microorganisms are challenged to adapt to the new conditions. In this study, various process parameters including pH value, CH4 production rate, conversion yields and final gas composition were monitored for a hydrogenotrophic-adapted microbial community cultivated in a laboratory-scale BM reactor. To investigate the robustness of the BM process regarding power oscillations, the biogas microbiome was exposed to five hydrogen (H2)-feeding regimes lasting several days. Applying various "on-off" H2-feeding regimes, the CH4 production rate recovered quickly, demonstrating a significant resilience of the microbial community. Analyses of the taxonomic composition of the microbiome revealed a high abundance of the bacterial phyla Firmicutes, Bacteroidota and Thermotogota followed by hydrogenotrophic Archaea of the phylum Methanobacteriota. Homo-acetogenic and heterotrophic fermenting Bacteria formed a complex food web with methanogens. The abundance of the methanogenic Archaea roughly doubled during discontinuous H2-feeding, which was related mainly to an increase in acetoclastic Methanothrix species. Results also suggested that Bacteria feeding on methanogens could reduce overall CH4 production. On the other hand, using inactive biomass as a substrate could support the growth of methanogenic Archaea. During the BM process, the additional production of H2 by fermenting Bacteria seemed to support the maintenance of hydrogenotrophic methanogens at non-H2-feeding phases. Besides the elusive role of Methanothrix during the H2-feeding phases, acetate consumption and pH maintenance at the non-feeding phase can be assigned to this species. Taken together, the high adaptive potential of microbial communities contributes to the robustness of BM processes during discontinuous H2-feeding and supports the commercial use of BM processes for energy storage. Discontinuous feeding strategies could be used to enrich methanogenic Archaea during the establishment of a microbial community for BM. Both findings could contribute to design and improve BM processes from lab to pilot scale.


Why is FERONIA pleiotropic?
The plant cell wall has many roles: structure, hydraulics, signalling and immunity. Monitoring its status is therefore essential for plant life. Among many candidate cell wall sensors, FERONIA, a member of the Catharanthus roseus receptor-like kinase-1-like kinase (CrRLK1L) family, has received considerable attention, notably because of its numerous interactors and its implication in many biological pathways. Conversely, such an analytical dissection may blur its core function. Here we revisit the array of feronia phenotypes as an attempt to identify a unifying feature behind the plethora of biological and biochemical functions. We propose that the contribution of FERONIA in monitoring turgor-dependent cell wall tension may explain its pleiotropy.


Rhizoremediation of a dioxin-like PCB polluted soil by alfalfa: Dynamic characterization at temporal and spatial scale.
This study investigates the temporal and spacial dissipation dynamics of a dioxin-like polychlorinated biphenyl (PCB 77) in the rhizosphere of alfalfa. A three-chamber rhizobox was designed to compare the PCB 77 dissipation efficiency in the rhizosphere, near-rhizosphere, and far-rhizosphere zones. Culture-independent techniques, including quantitative PCR (qPCR), Biolog-ECO plate, and denatured gradient gel electrophoresis (DGGE) were employed to investigate the variation of bacterial quantity, metabolic diversity and community structure in the alfalfa-rhizobium symbiosis rhizosphere at different rhizoremediation stages. PCB dissipation rates in different rhizosphere zones were in the order: rhizosphere (90.9%) > near-rhizosphere (80.5%) > far-rhizosphere (31.7%). The number of the bacterial 16S rRNA gene copies in the rhizosphere zone in the polluted treatment reached the highest value of all the treatments. Microbial metabolic diversity, as indicated by average well color development (AWCD) in both rhizosphere and near-rhizosphere zones, had recovered from the PCB 77 pollution. The soil bacterial community diversity improved greatly in the rhizosphere of alfalfa, with some new species appeared in the rhizosphere and near-rhizosphere zones. In conclusion, the dissipation of PCB 77, the quantity of total soil bacteria, soil microbial metabolic diversity, and soil microbial community structure were significantly improved in rhizosphere and near-rhizosphere zones of alfalfa.


Comments on "Mycobiota and Mycotoxins in Traditional Medicinal Seeds from China. Toxins 2015, 7, 3858-3875"- in Attributing Ochratoxin A Biosynthesis Within the Genus Penicillium Occurring on Natural Agricultural Produce.
The unusual attribution of trace amounts of ochratoxin A in some Chinese food commodities to Penicillium polonicum is questioned by European experience in searches for ochratoxinogenic food-spoilage Penicillia, where mistaken attribution is now known to have been due to cryptic Penicillium verrucosum contamination. Consequently, selection of single-spore isolates is recommended as pre-requisite for attributing mycotoxin biosynthetic potential to fungi.


Effects of decreased O2 and elevated CO2 on survival, development, and gene expression in cowpea bruchids.
Use of modified atmospheres with depleted O(2) and/or elevated CO(2) is an environmentally friendly alternative to currently used fumigants for control of stored grain insect pests. In the present study, we examined the impact of hypoxia and hypercapnia on cowpea bruchids (Callosobruchus maculatus), a storage pest of cowpea and other legumes. Two O(2)/CO(2) combinations were used; (i) 10% O(2)+10% CO(2), (ii) 2% O(2)+18% CO(2). In both cases, N(2) was maintained at 80%, equivalent to normal atmospheric concentration. In ambient atmosphere, the rate of O(2) consumption and CO(2) output at different stages (from low to high) was: eggs≈1st instar<2nd instar≈pupae≈adults<3rd instar<4th instar. When exposed to 10% O(2)+10% CO(2), eggs, larvae and pupae were able to complete development and successfully enter the next developmental stage, although developmental time and mortality varied at different stages. In contrast, more severe hypoxic/hypercapnic treatment, i.e. 2% O(2)+18% CO(2), led to cessation of development of all stages. Effects on eggs and adults were most dramatic as they could only withstand 2-3 days exposure. Further, eggs at early (4-6h old) and later stages (102-104 h old, black-headed) were more susceptible compared to those at intermediate stage (52-54 h old). The 3rd and 4th instar larvae were least sensitive and could survive up to 20 days treatment. To gain some insight into molecular mechanisms underpinning the hypoxic/hypercarpnic response, we performed qPCR reactions on selected metabolic genes involved in TCA cycle and in protein digestion, as well as genes encoding stress-responsive heat shock proteins. Patterns of gene expression and proteolysis suggest that cowpea bruchids suppress their metabolic activity and increase stress tolerance when challenged by O(2) deprivation. Transcript abundance as well as proteolytic activity recovered once normoxic conditions resumed. Taken together, cowpea bruchids were found able to cope with hypoxic and hypercapnic stress. This ability was particularly strong in the late larval stage.


Dimensional changes at the posterior border of baseplates made from a visible light-activated composite resin.
Dimensional changes of 50 baseplates made of Triad visible light-cured resin were measured before and after curing, placement in water, and drying on the laboratory bench. Results showed that the resin shrinks but improves on storage in water. For persons sensitized to monomer, no free monomer is present in the material. Therefore, Triad resin offers an alternative to conventional self-curing resins often used to make baseplates.


Plantar stimulation prevents the decrease in fatigue resistance in rat soleus muscle under one week of hindlimb suspension.
Support afferentation in recent years was shown to be a key physiological stimulus controlling postural muscle function, structure and phenotype. Lack of support afferentation under various types of muscle disuse leads to a decline of size and percentage of slow-type fatigue-resistant muscle fibers, which can negatively affect muscle performance and life quality. In this study we simulated support afferentation during rat hindlimb unloading and investigated its effect on postural soleus muscle functional properties and signaling. Plantar mechanical stimulation prevented the unloading-induced muscle fatigue increase, maintained the level of mitochondrial DNA copy number and the percent of slow-type muscle fibers and partially prevented the increase of CpG methylation in pgc 1α promoter region and decline in myonuclear content of several transcriptional activators of slow myosin and PGC1 α expression. So, support afferentation under hindlimb suspension leads to maintaining of a slow-twitch oxidative and fatigue-resistant soleus muscle fibers phenotype.


Elevated Endogenous Testosterone Levels are not Associated With Significant Clinical Morbidity.
To investigate the association between elevated endogenous testosterone levels and deleterious effects associated with testosterone therapy. Elevated serum testosterone levels in men receiving testosterone therapy have been associated with side effects, though precise thresholds above which these occur are unknown. Data on the association between naturally elevated endogenous testosterone levels and their physiologic effects is sparse. We examined National Health and Nutrition Examination Survey data between 2011 and 2016, analyzing men aged 18 and older not on testosterone or androgen ablation therapy, excluding men who had testosterone <300 ng/dL, to compare men with elevated testosterone (>800 ng/dL) to men with normal testosterone (300-800 ng/dL). We used multivariable logistic and linear regressions for comparison. After excluding men with testosterone levels <300 ng/dL, 3673 men met inclusion criterion. Only 146 (4%) of men had a testosterone >800 ng/dL. When compared to men with normal testosterone, men with high testosterone had similar rates of sleep disorders, urinary symptoms, and depression. Men with elevated testosterone had higher hematocrit regression coefficient (βi 1.30, 95% confidence interval [CI] 0.69-1.90 P < .01), AST (βi 8.48, 95% CI 0.31-16.66, P = .04) and ALT (βi 12.23, 95% CI 0.70-23.77, P = .04) compared to men with normal testosterone. No association was found between higher endogenous testosterone levels and adverse events associated with testosterone therapy. Men with higher testosterone had increased hematocrit, but this was not clinically significant. This challenges what is considered a safe target for testosterone therapy and prompts future prospective studies to delineate the safety of elevated endogenous and exogenous modulated levels of testosterone.


Common problems in wound care: wound and ulcer measurement.
Accurate measurement is an important part of wound assessment. Wounds vary considerably in their nature, shape and site. Many measurement techniques exist. It is important to choose the correct technique for a specific wound and to understand the degree of accuracy obtained from the measurements.


[Linkage disequilibrium study of microsatellite markers on chromosome 6 and schizophrenia].
To explore the relationship between the microsatellite markers on chromosome 6 and schizophrenia by linkage disequilibrium analysis. Twenty-eight microsatellite markers on chromosome 6 were evaluated in 115 affected-sib-pair and trios families. Linkage disequilibrium analysis was conducted according to diagnostic categories, Positive and Negative Syndrome Scale (PANSS) and other clinical data by XDT and MAPMAKER/SIBS software system. Significant P value (P<0.005) was found in all the four diagnostic categories. Only the locus of D6S1960 showed positive P value (P<0.05) in all the subgroups divided by PANSS scale and the age of onset. The area around D6S1960 in short arm of chromosome 6 may contain susceptibility gene of schizophrenia.


Bone healing.
Secondary fracture healing with callus fomation involves the immediate reaction of this special kind of connective tissue (as well as others) with rapid increase in the reduplication of periosteal, paraosseal, and, to a lesser extent, endosteal cells. There is increased metabolism of glycosaminoglycan collagen synthesis, and transformation of fibrous and cartilaginous callus, combined with mineralization of the latter and intensified vascular invasion into bone. The glycosaminoglycan content decreases with progressing ossification, while the collagen content increases. In the beginning stages of whole bone fracture healing, vascularization is the first step responsible in part for the several maxima of synthesis and total contents of the specific cell products. Extension of ossification and remodeling in the final phases of bone fracture healing depend on other local and general factors, as well as biophysical and biological factors.


Role of protein kinase C as a cellular mediator of ischemic preconditioning: a critical review.
Protein kinase C (PKC) has been proposed as a primary cellular mediator of ischemic preconditioning. However, the role of PKC in eliciting cardioprotection remains controversial. In this review, we summarize the evidence for and against the 'PKC hypothesis' of preconditioning, discuss the important technical limitations currently hampering PKC research, and suggest new approaches (i.e. PKC isoform-specific biochemical assays combined with immunoblotting techniques) that might aid in the definite resolution of this issue.


Quality of life assessment before and after lumbar disc surgery.
Although operative treatment for lumbar disc herniation is a commonly performed neurosurgical procedure, no reports have described whether health-related quality of life before surgery affects the operative treatment outcome. This prospective study assessed health-related quality of life before and after surgery and evaluated the predictor variables affecting outcomes. Subjects were 45 consecutive candidates for lumbar disc herniation surgery who gave informed consent. The Medical Outcomes Study Short Form 36 (SF-36) and 15-point Japanese Orthopaedic Association (JOA) score were evaluated before and after surgery, and the magnitude of the effect was calculated. The possible predictor variables for outcomes were physical functioning, role physical, bodily pain, general health, vitality, social functioning; role emotional and mental health from the SF-36 subscales; subjective symptoms and clinical signs from the JOA scores; and the patient's age, sex, occupation, and history of low back pain and/or leg pain. Four patients were excluded from the analyses because they were lost to follow-up within 1 year after operation. All subscales of the SF-36 and JOA scores increased significantly at 6 months and 1 year of follow-up with a maximum effect size in bodily pain and a minimal in general health. Operation results were 29 good, 11 fair, and 1 poor. The selected predictor variables affecting the outcomes were patient age and social functioning on SF-36. Surgery for lumbar disc herniation improved health-related quality of life. Patients <50 years old with a <60 score in social functioning on SF-36 were considered good candidates.


Oral and pharyngeal cancer: analysis of patient delay at different tumor stages.
The aim of this study was to examine which factors are related to patient delay in a cohort of consecutive patients with pharyngeal cancer and oral cancer and to determine whether the different stages of patient delay (ie, appraisal, illness, behavioral, and scheduling) were related to different tumor stages. Before treatment, 55 patients with pharyngeal cancer and 134 patients with oral cancer were interviewed about their prediagnostic period. To verify the data, a questionnaire was sent to the general practitioner and/or dentist and a close relative. Patients with a delay of more than 30 days were significantly more often diagnosed with late-stage (T3-T4) disease (pharynx, p = .01, odds ratio [OR] = 4.5; oral, p = .01, OR = 3.2). No sociodemographic characteristics were associated with patient delay. Prolonged patient delay was associated with late-stage disease for both patients with pharyngeal cancer and patients with oral cancer. Although for most patients the symptoms are vague or might look like a common cold or infection, the general public should be better informed about tumor symptoms. This may enhance earlier visits to a health care professional.


Discovering fashion industry trends in the online news by applying text mining and time series regression analysis.
The growth of digital media usage has accelerated the development of big data technology. According to the agenda-setting theory, news media inform the public regarding major agendas and business cycles. This study investigated 168,786 news documents from 2016 to 2020 related the South Korea fashion business using Python. A total of 19 topics were extracted through latent Dirichlet allocation and then transformed into structured data using a time series approach to analyze significant changes in trends. The results indicate that major fashion industry topics include business management strategies to increase sales, diversification of the retail structure, influence of CEOs, and merchandise marketing activities. Thereafter, statistically significant hot and cold topics were derived to identify the shifts in topic themes. This study expands the fashion business contexts with agenda-setting theory through big data time series analyses and can be referenced for the government agencies to support fashion industry policies.


Increase in use of protective earplugs by Rock and Roll concert attendees when provided for free at concert venues.
To determine the prevalence of hearing protection use among attendees of Rock and Roll concerts at baseline and in concerts where earplugs are provided for free at concert venue entrances. Six concerts performed at two music venues in Toronto, Canada were evaluated. Study personnel observed and recorded the use of hearing protection at three concerts where no earplugs were distributed, and three concerts where earplugs were provided for free at the concert venue entrance. A total of 955 individuals over the age of 18 were observed at six concerts. Six hundred and thirty-seven individuals (64% male) were observed at concerts where no earplugs were provided, and 318 individuals (68% male) were observed at concerts where free earplugs were provided. Multivariate logistic regression demonstrated a significant increase in hearing protection usage at concerts where earplugs were provided for free at the concert venue entrance, odds ratio 7.27 (95% CI: 3.24-16.30). The provision of free earplugs at concert venues may be a simple and inexpensive intervention that could be a component of a larger public health campaign to prevent non-occupational noise-induced hearing loss.


An auditory Stroop effect for pitch, loudness, and time.
Increased reaction time to pitch, loudness, or duration of an auditorily presented word whose meaning is in conflict with the response label (i.e., high/low, loud/soft, or fast/slow) demonstrates an auditory Stroop effect. Fifteen normal adults participated in an auditory Stroop test. Analysis of reaction time data supports the existence of an auditory Stroop effect for pitch and loudness, but not duration. The interaction between psychoacoustic and semantic attributes of speech stimuli is discussed.


In vitro activity of lomefloxacin and other antimicrobials against bacterial enteritis pathogens.
Lomefloxacin is a new, difluoroquinolone. In this study, the in vitro activity of lomefloxacin against clinical isolates of a variety of bacterial species associated with acute diarrheal disease was determined and compared with that of ciprofloxacin, ofloxacin, amoxicillin, sulphamethoxazole, trimethoprim, tetracycline, and chloramphenicol. Bacterial isolates were obtained from different geographical areas, including Western Europe and the United Kingdom, Southern Europe, Africa, the Middle East, South and Southeast Asia, and South America, and were included to reflect the range of susceptibility seen throughout the world. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton medium supplemented when necessary with saponin-lysed horse blood at a final concentration of 10% vol/vol. Lomefloxacin was highly active against all the species examined which included Salmonella spp., Shigella spp., Escherichia coli enterotoxigenic [(ETEC), enteroinvasive (EIEC), and enteropathogenic (EPEC) strains], Yersinia enterocolitica, Campylobacter jejuni, Vibrio spp., and Aeromonas hydrophila, with all isolates inhibited by 1 mg/L or less. This activity was similar to ofloxacin and slightly less than that of ciprofloxacin. By contrast, many of the isolates were resistant to one or more of the other, unrelated animicrobials. No cross-resistance between lomefloxacin and any of the nonfluoroquinolone antimicrobials examined in the study was observed.


High regioselective ultrasonic-assisted synthesis of 2,7-diaryl-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids.
New and high regioselective method of the synthesis of 2,7-diaryl-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids by reaction of 3-aryl-5-aminopyrazoles with arylidenpyruvic acid at room temperature under ultrasonication was developed and discussed.


Fragile sites and statistics.
A simple and reliable statistical method is proposed to distinguish real fragile sites from the casual accumulation of aberrations that can occur as a consequence of random distribution. It is based on a study of the expected random distribution, assumed to be equal to a Poisson distribution, with the expected value of events per band as the mean.


The phenomenon of formation of prebiological compounds in volcanic processes.
Organic matter has been found in the juvenile ash of seven volcanoes in Kamchatka, the Kurile Islands and Indonesia. Its amount in one eruption is of the order of 1 00 000 tons. This matter constitutes a multicomponent mixture (more than 150 components) of, mainly, high boiling (b.p. over 250 degrees C) organic compounds of a complex structure. These are represented by hydrocarbons of saturated and aromatic nature, and, among them, polycyclic hydrocarbons, amino acids, amino sugars and other heteroatomic molecules, also containing N, O, S and C1. The formation of the above mentioned organic compounds is associated with volcanic processes--with abiogenous synthesis taking place in ash-gas clouds and, possibly, in the entrails of the Earth (hydrocarbons and their heteroatomic derivatives have also been found in volcanic bombs). On the strength of these facts, volcanic phenomena are regarded as the process which serves as the starting point of the chemical evolution from the inanimate to the animate matter.


Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus.
The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.


Non-invasive detection of coronary artery disease by dobutamine-stress echocardiography in children after heart transplantation.
Coronary vasculopathy is the main cause of cardiac graft failure. Because yearly coronary angiography is invasive in children, a non-invasive method for detecting graft vasculopathy is needed. The aim of this study was to test dobutamine-stress echocardiography in a pediatric population to determine its feasibility, safety and reliability in the detection of graft coronary artery disease. Eighteen patients, aged 2 days to 16.8 years at transplantation (mean 8.4 years), underwent 44 dobutamine-stress echocardiography (DSE) exams, at a follow-up of 1.1 to 11.8 years (mean 5.1 years). Selective coronary angiography was performed for comparison. Echocardiographic recordings were obtained in 4 standard views of the left ventricle and measurements carried out within the frames of a 16-segment model. Segmental scores of contractility were obtained for each segment and a total segmental contractility index was calculated at each stage. All patients reached the maximum dose stage. Maximum heart rate was 57% to 90% of predicted maximum. Maximum systolic blood pressure reached 190 mmHg. Segmental scores were normal in 37 and abnormal in 7 cases. Echographic results were concordant with angiography in 82% and discordant in 18% of the cases (4 negative DSEs with minor angiographic lesions, 2 positive DSEs with normal angiography), but there was no significant angiographic lesion with normal DSE. DSE is a safe and highly feasible non-invasive technique in transplanted children. A normal DSE study successfully predicts the absence of significant coronary artery disease in the post-transplant population.


Comparison among T1-weighted magnetic resonance imaging, modified dixon method, and magnetic resonance spectroscopy in measuring bone marrow fat.
An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods.


Re-evaluation of CO₂ laser myringotomy for managing children with persistent acute otitis media.
This study aimed to re-evaluate the utility of CO(2) laser myringotomy in children with persistent acute otitis media (PAOM). From September 2002 to April 2008, 40 children with PAOM received CO(2) laser myringotomy. PAOM was defined as continuing symptoms and signs after systemic antibiotic treatment. Before laser myringotomy, the eardrums were checked under videotelescopy, pure tone audiometry or behavior audiometry and tympanometry. Middle ear effusions were collected using our own designed bottle culture device after laser myringotomy. The patients were followed up at outpatient clinics for 3 months. Cultured middle ear pathogens, healing time of the eardrums, hospital course (for admitted patients), and the development of middle ear effusions were recorded. Forty children with 53 ears with PAOM were enrolled. Eight patients (20%) had bilateral disease and underwent bilateral laser myringotomy. The overall culture rate was 28.3%, and Streptococcus pneumoniae was the most common pathogen. Eight patients (20%) were admitted for intravenous antibiotics. The average eardrum healing time was 22 days in those with positive cultures, and 16.4 days in those with negative cultures (p=0.125). All eardrums healed in 1 month. The resolution rate was 62.5% at 1 month. Patients with bilateral PAOM were prone to have positive middle ear culture (5/8) compared with those with unilateral PAOM (8/32) (p=0.086). CO(2) laser myringotomy is an applicable means of treating PAOM. S pneumoniae is the most common pathogen in PAOM. CO(2) laser myringotomy allows for the drainage and culture sampling of middle ear effusion, relieving the need of taking prolonged medication.


A maize cryptic Ac-homologous sequence derived from an Activator transposable element does not transpose.
Sequences sharing homology to the transposable element Activator (Ac) are prevalent in the maize genome. A cryptic Ac-like DNA, cAc-11, was isolated from the maize inbred line 4Co63 and sequenced. Cryptic Ac-11 has over 90% homology to known Ac sequences and contains an 11 bp inverted terminal repeat flanked by an 8 bp target site duplication, which are characteristics of Ac and Dissociation (Ds) transposable elements. Unlike the active Ac element, which encodes a transposase, the corresponding sequence in cAc-11 has no significant open reading frame. A 44 bp tandem repeat was found at one end of cAc-11, which might be a result of aberrant transposition. The sequence data suggest that cAc-11 may represent a remnant of an Ac or a Ds element. Sequences homologous to cAc-11 can be detected in many maize inbred lines. In contrast to canonical Ac elements, cAc-11 DNA in the maize genome is hypermethylated and does not transpose even in the presence of an active Ac element.


Adipose mesenchymal stem cells-derived exosomes alleviate osteoarthritis by transporting microRNA -376c-3p and targeting the WNT-beta-catenin signaling axis.
Osteoarthritis (OA), one of the major diseases afflicting the elderly, is a type of degenerative joint disease related to cartilage and synovium. This study aimed to clarify the role and mechanism of adipose mesenchymal stem cell (ADSC)-derived exosomes (Exos) in OA-induced chondrocyte degradation and synovial hyperplasia, thus improving the quality of life of patients. The rat OA model, chondrocytes, synovial fibroblast models and immunofluorescence were applied to observe the in vivo and in vitro functions of human ADSC (hADSC)-derived Exos in OA and its possible regulatory signaling pathways. Bioinformatics software and luciferase reporter assay were carried out to verify the mechanism of microRNA-376c-3p (miR-376c-3p) in hADSC-derived Exos in OA in vitro. Moreover, Safranine O-Fast Green Cartilage staining, Masson staining, immunohistochemistry and immunofluorescence were conducted to verify the role of miR-376c-3p in hADSC-derived Exos in OA in vivo. hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis both in vivo and in vitro models by repressing the WNT-beta-catenin signaling pathway. For the mechanism exploration in vitro, miR-376c-3p was raised in hADSC-derived Exos and mediated the fibrosis of synovial fibroblasts in OA, and miR-376c-3p targeted the 3'-untranslated region of WNT3 or WNT9a. Meanwhile, the in vivo experiments also corroborated that the miR-376c-3p in hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis. MiR-376c-3p in hADSC-derived Exos repressed the WNT-beta-catenin pathway by targeting WNT3 or WNT9a, and then mitigating OA-induced chondrocyte degradation and synovial fibrosis, thereby providing theoretical basis for clinical implementation of treatment.


Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning. I. Pavlovian conditioning.
We have previously obtained evidence that the mesoamygdaloid dopamine projection modulates the acquisition of a conditioned response (CR) elicited by presentation of a conditioned stimulus (CS) predicting the availability of a natural (sucrose) reward. This property was found to be dependent upon D3, but not D1 or D2, dopamine receptor activation. The aim of the present study was to determine whether the mesoamygdaloid dopamine projection is similarly involved in the acquisition of a drug-associated CR. Thus, two groups of rats with guide cannulae aimed at the nucleus accumbens and amygdala were trained using a Pavlovian conditioning procedure in which an initially neutral CS was paired with a computer-controlled, bilateral intraaccumbens infusion of d-amphetamine (the unconditioned stimulus: US). Conditioning sessions were conducted in standard operant chambers, with each session consisting of a single CS-US trial. For one group of rats, CS presentation was positively correlated with the drug US (Paired group), while for the second group CS and US presentations were negatively correlated (Unpaired group). During training, locomotor activity was recorded and was utilised as the measure both of the unconditioned (UR) and conditioned response (CR). A within-subjects design was utilised to investigate the effect of post-session bilateral intraamygdala administration of R(+) 7-OH-DPAT on the development of the drug-associated CR. Hence, both Paired and Unpaired groups were exposed to two different CSs which were presented on alternate sessions. Post-session bilateral intra-amygdala administration of R(+) 7-OH-DPAT (10 nmol) followed sessions in which one CS was presented, while intra-amygdala vehicle followed sessions in which the alternate CS was presented. The development of a CR occurred only in the presence of a CS that had been positively correlated with presentation of the drug US. Post-session, intra-amygdala administration of R(+) 7-OH-DPAT enhanced the acquisition of this CR. However, R(+) 7-OH-DPAT was without effect upon the unconditioned response to intra-accumbens d-amphetamine. Our previous data indicate a comparable effect of R(+) 7-OH-DPAT on conditioning to a CS associated with a non-drug, natural reward. Therefore, taken together, these findings suggest that D3 dopamine receptors within the amygdala modulate specifically the acquisition of Pavlovian conditioned responses, regardless of whether drug or natural rewards constitute the US.


Youth and family members make meaningful contributions to a randomized-controlled trial: YouthCan IMPACT.
There are growing calls to engage service users in research about issues relevant to them. Youth and family members can make meaningful contributions to research projects, improving quality and relevance. However, more information is needed on the contributions that youth and family members can make to various study designs. This paper describes the contributions that youth and family members have made to a multi-site pragmatic randomized-controlled trial, YouthCan IMPACT, and the way project-based engagement learnings accelerated change at the institutional level and beyond. Youth and family members were full members of the project team, including the project's core governance and working groups. They contributed to project leadership, as funding co-applicants and as equal members of the governance team. They were also engaged in study design. Youth defined the primary outcome measure and contributed to decisions on all secondary measures. The service pathway was co-designed with youth and family members; for example, they guided the inclusion of peer support and a family member intervention as core service components. Study implementation contributions included ensuring a youth- and family-friendly research process and training research staff on working with youth and family members. Knowledge translation activities have included youth and family members as co-presenters and manuscript co-authors. The learnings from this trial have been leveraged to expand youth and family engagement at the institution and beyond. Youth and family members make substantial contributions to complex research projects, including randomized-controlled trials, thereby improving project design, study implementation, associated interventions, and knowledge translation.


A negative association of HLA-BW52 with Graves' disease and insulin-dependent diabetes mellitus with juvenile onset among Japanese population.
The present study demonstrated that a decreased frequency of HLA-BW52 was a common characteristic shared by the patients with Graves' disease and insulin-dependent diabetes mellitus with juvenile onset among Japanese.


New technique for open placement of paddle-type spinal cord stimulator electrode in presence of epidural scar tissue.
The objective of this study is to present a novel surgical technique for safe placement of paddle-type spinal cord stimulation (SCS) electrode in the presence of epidural scar tissue. We developed a new surgical technique for placement of paddle-type SCS electrode in presence of epidural scar tissue when conventional placement methods had failed. The technique involves creating a laminotomy trough to provide an adequate window for dissection of scar tissue to ensure safe placement of the electrode. We have applied this technique in eight patients. Safe placement of SCS electrode was achieved in all eight patients without any complications. All electrodes were placed between T8 and T10 levels, and we were able to place the electrodes in the midline and achieve adequate coverage in all cases. SCS is a widely accepted treatment modality for chronic neuropathic pain. Placement of paddle electrode can be challenging, usually because of the presence of epidural scar tissue. There have been reported cases of spinal cord injury related to paddle electrode placement. We present a novel technique that allows for safe placement of a paddle-type SCS electrode in more challenging surgical circumstances, including the presence of epidural scar tissue.


Structural analysis of polysaccharide/antisense DNA complexes during cytoplasmic target mRNA hybridization.
We previously demonstrated antisense oligonucleotides (AS-ODNs) delivery system based on the complex formed with poly (dA) and schizophyllan, a type of β-1,3-glucan. This complex enables efficient intracellular delivery of AS-ODNs. In this communication, we investigated the cytoplasmic translocation of the complex itself and its mechanism of action on mRNA. As a result, we found that the complex moved into the cytoplasm while keeping its structure, and AS-ODN hybridized with the target mRNA. This result encourages pharmaceutical applications of the complex.


Mutagenicity of metal ions in bacteria.
The mutagenicity of 24 metal salts was investigated in plate incorporation and fluctuation assays with Salmonella TA strains or Escherichia coli WP2 uvrA pKm 101. Chromate(VI) and selenate(VI) ions were found to be mutagenic in plate incorporation assays employing conventional media. On the other hand, cadmium(II), beryllium(II), chromate(VI), and metavanadate(V) ions were detected in conventional fluctuation assays, indicating the importance of this technique in detection of metal mutagens. Modified culture media, with trimetaphosphate ions in place of orthophosphate as the sole phosphate source for bacterial growth, were also used in this study. The media modifications prevented precipitation of metals such as nickel and cadmium as their insoluble phosphates, and allowed detection of the mutagenicity of metavanadate ions in plate incorporation assays. However, the fluctuation technique using standard media was shown to detect a wider range of mutagenic metal ions than tests with modified media. It is notable that metaarsenite(III), arsenate(V), and nickel(II) ions were not found to be mutagenic in any of the assays although they are known to be carcinogenic and are mutagenic in other test systems. Their lack of mutagenicity in the modified media indicates that precipitation of these ions as orthophosphates is not the reason for their lack of activity in standard bacterial assays.


An explicit expression for the retention factor and velocity dependency of the mobile zone mass transfer band broadening in packed spheres beds used in liquid chromatography.
The present study proposes a ready-to-use analytical expression to calculate the mobile zone mass transfer contribution (hCm) in packed bed columns. For this purpose, first high-accuracy computations of the band broadening in a perfectly ordered sphere array (fcc-arrangement, external porosity ε=0.40) were made using computational fluid dynamics (CFD), covering a broad range of zone retention factors (2≤k''≤18) and reduced velocities (0≤νi≤48). Subsequently, these data were used to determine the value of the geometrical constants in a number of possible analytical expressions for the hCm-contribution. This fitting exercise showed the traditional literature approach, using the Wilson-Geankoplis correlation to calculate the dimensionless Sherwood (Sh) number for the mass transfer, leads to fitting errors on the hCm-term as large as 150%. Instead, a new correlation for Sh is established. In addition, we also explored the difference in fitting accuracy between hCm-expressions based on either a plug-flow or a laminar flow profile assumption. Surprisingly, no significant difference in fitting accuracy between both assumptions was observed. Finally, a best-fit analytical expression is proposed that can represent the CFD-computed band broadening data with an average absolute fitting error of Δh=0.005, corresponding to a relative error of 2.5% on the hCm-term and of only 0.3% on the total plate height in a perfectly ordered sphere packing. Defining the presently investigated fcc-ordered sphere array with external porosity=40% as the reference geometry for a perfect sphere packing, the established expression can be used as a new yardstick expression against which the degree of eddy-dispersion can be measured.


[Interbody metal implants ("cages") for lumbar fusion].
Over the last 15 years, interbody metal implants have become commonly used worldwide for lumbar interbody fusion. The so called "cages" are made of metal or absorbable materials. By using different surgical techniques, they can be implanted either regularly or via endoscopy. The published results on surgical techniques using cages for the lumbar spine show, in most cases and with or without additional instrumentation, rates of fusion of more than 90%. It seems that the use of osteoinductive substances (especially BMP) leads to even better results. Dorsoventral fusion with internal fixation and bone show the same rate of consolidation, but the advantages of cages are primarily in the maintenance of the distraction and the possibility of a single surgical procedure without additional instrumentation (including endoscopy), and in a lower donor side morbidity.


Phosphatase and tensin homologue deleted on chromosome 10: extending its PTENtacles.
Since its discovery in 1997, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has become one of the most important molecules in tumor biology. Mutations, deletions or dysregulation of PTEN is found in many human tumors. Recent studies have extended the reach of PTEN to include diabetes and neurological diseases such as Parkinson's and autism. In this review, we summarize the traditionally characterized function of PTEN as the lipid phosphatase that dephosphorylates PI-3,4,5-P(3), and several other newly discovered functions. The inhibition of the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway may account for most of PTEN's tumor suppressing function. However, other growth inhibiting functions of PTEN may not involve this pathway. PTEN can also inhibit growth through its protein phosphatase activity and in ways not related to its enzymatic activity at all. We survey the many functions and biochemical interactions of PTEN in cytoplasm, the nucleus and throughout the cell in this paper.


Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis.
The role of forebrain cholinergic projections in place navigation learning was assessed in two experiments. Following surgery, rats were required to learn the spatial location of an underwater platform on the basis of distal room cues. Bilateral injections of ibotenic acid into the nucleus basalis magnocellularis depleted choline acetyltransferase (ChAT) from the anterior and temporoparietal cortex but not the hippocampus. Separate histological studies confirmed the accuracy of the lesions and demonstrated a marked loss of cortical acetylcholinesterase. These rats subsequently showed no deficits in spatial learning or memory. In a second experiment, bilateral lesions of the vertical limb of the diagonal band of Broca and medial septum depleted ChAT from the hippocampus and posterior cortex but not the anterior cortex. Histological studies confirmed the accuracy of the lesion and showed a pronounced loss of acetylcholinesterase from the hippocampus. These rats were deficient in spatial learning and showed reduced spatial bias during transfer tests. The data are discussed in the light of the hypothesis that the cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation.


Reproductive behaviour of the ocean skater Halobates robustus (Hemiptera: Gerridae) in the Galapagos Islands.
Field observations on the ocean skater, Halobates robustus Barber showed that the flotillas of adults, unlike those of juveniles, occurred very close to the shore at specific sites from which they were not easily dislodged.The adult flotillas consisted of small all-male groups or aggregations of males and copulating pairs. The proportion of free males in copulating flotillas decreased with increasing group size. There was no correlation between the sizes of the paired males and females.Single adult females, which were not observed in the copulating flotillas, were usually teneral with undeveloped eggs. In contrast, the copulating females contained numerous well-developed eggs. The pairs remained in prolonged genital contact.The behaviour of free males in copulating flotillas was characterized by frequent, non-random encounters with copulating pairs. Experiments with marked individuals established that male take-overs can occur within flotillas.It is concluded that the copulating flotillas are initiated by the males and not only provide protection from predators, as previously shown, but also act as arenas for mate finding and selection. It is presumed that prolonged copulation reduces sperm competition between contending males.