Structure and function of native and refolded peridinin-chlorophyll-proteins from dinoflagellates.
Peridinin-chlorophyll a-proteins are a class of light-harvesting proteins only found in photosynthetic dinoflagellates. Due to their exceptional stability they are an excellent model system to study carotenoid to chlorophyll energy transfer. We were able to solve structures of these complexes at near atomic resolution, allowing the detailed discussion of pigment-pigment and pigment-protein interactions. Using a refolding system, we also determined structures of complexes with mutated apoproteins and modified pigment compositions. Here we summarize the current understanding of PCP structures, with an emphasis on how the basic dimeric structure may be modified in the oligomeric state of these complexes.


Rapid-extraction oxidation process to recover and reuse copper chromium and arsenic from industrial wood preservative sludge.
Chromated copper arsenate (CCA) wood preservative can form insoluble sludges when the hexavalent chromium component is reduced by wood extractives, wood particles and preservative additives in the solution. This sludge accumulates in treating solution work tanks, sumps and in-line filters and must be disposed of as hazardous wastes by waste disposal companies at high costs. A number of commercial sludges were investigated and found to contain 18-94% copper, chromium and arsenic as oxides combined with sand, oil, wood particles, additives and wood extractives. We have developed a multi-stage recycling process whereby approximately 97% of the CCA components are recovered from the sludge. It involves extraction with sodium hypochlorite to remove and oxidize chromium (more than 90%) and extract most of the arsenic (approx. 80%) followed by extraction of the copper and remaining arsenic and chromium with phosphoric acid. The phosphoric acid extract contains some trivalent chromium, which is subsequently oxidized by sodium hypochlorite. The combined oxidized extract containing CrVI, CuII and AsV was compatible with CCA treating solutions and could be re-used commercially for treating wood without having a significant effect on the preservative fixation rate or the leach resistance of the treated wood. A cost analysis showed that the economic savings from recovery of CCA chemicals and reduced landfill costs exceeded the variable costs for materials and energy for the process by as much as Can $966 per tonne of sludge if sodium sulfite can be acquired in bulk quantities for the process.


Histochemical localization of calcium ATPase in the cochlea of the guinea pig.
The activity of Ca(2+)-ATPase in the inner ear of the guinea pig was studied ultracytochemically by the lead citrate reaction. The electron-dense reaction products as an expression of Ca(2+)-ATPase activity were localized in endolymphatic cells of Reissner's membrane, in outer and inner hair cells and in some supporting cells. The main finding was the difference in the localization of Ca(2+)-ATPase in outer and inner hair cells. In the latter cells the activity sites were mainly intracellular and in apical membrane specializations, whereas in the outer hair cells the enzyme was localized in the apical membrane specializations and the basolateral plasma membrane.


Transcription-mediated tissue-specific lignification of vascular bundle causes trade-offs between growth and defence capacity during invasion of Solidago canadensis.
Allocation of more resources to growth but less to defense causing growth vigor of invasive alien plant populations contributes to successful invasion. However, few studies has addressed to relationship between vascular development variation and this mechanism. In this study, a common garden experimentwas established to compare the growth and vascular bundle development between native and introduced populations of Solidago canadensis, which is a wide-distributed invasive species in China. Our results suggested that the rapid growth of introduced populations could be explained by the well-developed and highly lignified xylem; while native populations present more developed and highly lignified phloem, which contributed more resistance to the infection of Sclerotiun rofsii compared with introduced populations. This difference was resulted from tissue-specific tradeoff distribution of lignification related gene expression between xylem and phloem, which is regulated by upstream MYB transcription factors. Our study gives a novel insight of mechanism that explain invasion success: lignin-related gene transcription-mediated tissue-specific lignification of vascular bundle contributes tradeoffs in resource allocation between growth and defence capacity during successful invasion of S. canadensis.


Multicenter phase 2 study of romidepsin plus lenalidomide for previously untreated peripheral T-cell lymphoma.
Peripheral T-cell lymphomas (PTCLs) are associated with poor prognosis when treated with cytotoxic chemotherapy. We report the findings of a phase 2 study evaluating a chemotherapy-free combination of romidepsin plus lenalidomide as initial treatment for patients with PTCL who were aged >60 years or noncandidates for chemotherapy. Treatment was initiated with romidepsin 10 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg taken orally from days 1 to 21 of 28-day cycle for up to 1 year. The primary objective was overall response rate (ORR). Secondary objectives included safety and survival. The study enrolled 29 patients with a median age of 75 years, including 16 (55%) angioimmunoblastic T-cell lymphoma (AITL), 10 (34%) PTCL- not otherwise specified, 2 ATLL, and 1 EATL. Grade 3 to 4 hematologic toxicities included neutropenia (45%), thrombocytopenia (34%), and anemia (28%). Grade 3 to 4 nonhematologic toxicities included hyponatremia (45%), hypertension (38%), hypoalbuminemia (24%), fatigue (17%), hyperglycemia (14%), hypokalemia (14%), dehydration (10%), and infection (10%). At median follow-up of 15.7 months, 23 patients were evaluable and received a median treatment of 6 cycles. The ORR was 65.2% with complete response (CR) at 26.1%, including 78.6% ORR and 35.7% CR for AITL. Median duration of response was 10.7 months, with 27.1 months for patients achieving CR. The estimated 2-year progression-free survival was 31.5%, and 2-year overall survival was 49.5%. This study provides the first demonstration that the biologic combination of romidepsin and lenalidomide is feasible and effective as initial therapy for PTCL and warrants further evaluation. This trial was registered at www.clinicaltrials.gov as #NCT02232516.


Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate.
CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries. Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects. This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection. Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included. Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3-5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter. Follow-up examinations were carried out after 3 (cytology, colposcopy, HPV DNA testing, and if needed re-PDT) and 6 months. Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively. Treatment could be accomplished in all cases and no severe side effects were encountered. Fifteen out of the 24 patients had a complete response (15/24 = 63%) and a HPV remission 6 months after 1-3 treatments. The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3. HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis.


In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis.
Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs. In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto (s.s.) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study. These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 μM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s., which may be the mechanism by which these drugs produce their therapeutic effects. Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.


Heart rate variability during extracorporeal membrane oxygenation and recovery in severe neonatal disease.
Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS) in neonates. During severe illness, heart rate variability is impaired. This study was initiated to measure the changes in HRV in neonates during extracorporeal membrane oxygenation (ECMO) and recovery from severe respiratory and circulatory failure. Moreover, we compared our data with HRV data of healthy newborns and we investigated the differences in HRV parameters between ECMO-survivors and non-survivors. This study is of an observational character. We performed short-term recordings of heart rate variability in 14 neonates during ECMO and recovery. We computed time- and frequency-domain HRV parameters. ECMO significantly affects time-domain HRV parameters. Severe neonatal illness causes a significant reduction of all calculated HRV parameters; clinical recovery is accompanied by an increase of HRV. In comparison with normative data of healthy newborns, however, HRV remains impaired. The ECMO-development ratio separated the non-survivors from the survivors during ECMO therapy. During severe neonatal illness, HRV is impaired. It remains to be clarified whether the impairment of HRV during severe illness can predict the neurological outcome. The ability of the E/D ratio as an HRV parameter to serve as a predictive tool has to be corroborated in larger group of patients.


Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients.
We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n = 32). In multivariate analysis the only two significant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graft-versus-host disease (GvHD, P < 0.0001; OR 4.6) and having received steroid prophylaxis for GvHD (P = 0.04; OR 2.1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0.0001; OR 5.6), non-early disease phase (P = 0.0001; OR 1.9), steroid prophylaxis (P = 0.02; OR 1.4), moderate-to-severe GvHD (P = 0.01; OR 1.6) and cytomegalovirus infection post transplant (P = 0.001; OR 1.8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors.


Epstein-Barr virus integration in human lymphomas and lymphoid cell lines.
Epstein-Barr virus (EBV) is maintained as an episome in most infected cells. The presence of fused terminal restriction enzyme fragments distinguishes the circular DNA form from the linear virion form. EBV genomic structure was analyzed in 8 lymphoid cell lines and 21 human lymphoma specimens by the Southern blot technique. Evidence of viral integration into host chromosomal DNA was identified in four cell lines. In the Namalwa and BL30-B95.8 cell lines, integration occurred through the terminal repeat (TR) sequences. In the BL41-P3HR1 and BL41-B95.8 cell lines, there was loss of left-end viral genomic sequences, including ori-P sequences required for episome maintenance, implying that integration was required for viral genome persistence. Integration was not detected in four other cell lines (Raji, Daudi, B95.8, and BL30-P3HR1). In 21 EBV-containing human lymphomas, including 18 immunodeficiency-related lymphomas, fused TR sequences were identified without evidence of viral genomic integration. These findings suggest that, although viral integration is common in Burkitt lymphoma cell lines infected in vitro, integration is not common in human lymphomas that develop in vivo in normal or immunodeficient people.


Separate requirements for detection and perceptual stability of motion in interocular suppression.
In interocular masking, a stimulus presented to one eye (the mask) is made stronger in order to suppress from awareness the target stimulus presented to the other eye. We investigated whether matching the features of the target and the mask would lead to more effective suppression (feature-selective suppression), or not (i.e., non-selective suppression). To control the temporal characteristics of the stimuli, we used a dynamic interocular mask to suppress a moving target, and found that neither matching speed nor pattern of motion led to more effective suppression. Instead, a faster target was detected faster, regardless of the mask type or speed, while a relatively slow (about 1°/s) mask was more perceptually stable (i.e., maintained suppression longer) in a non-selective fashion. While the requirement for target detectability, i.e., salience, is well characterized, relatively little attention is given to the factors that make a mask percept more perceptually stable. Based on these results, we argue that there are separate requirements for detection and perceptual stability.


Selective deprivation of paradoxical sleep and consolidation of shuttle-box avoidance.
Investigated whether paradoxical sleep is implicated in the storage of information acquired during shuttle-box avoidance. Wistar rats were given 5 brief training sessions distributed over the light period of the diurnal cycle. During the intervals between sessions the animals were selectively deprived of paradoxical sleep by awakening them every time they showed this type of sleep. The onset of paradoxical sleep was identified when hippocampal theta rhythm occurred during behavioural sleep. Yoked control animals got the same treatment irrespective of their sleep-waking behaviour, whereas free sleep rats were allowed to sleep undisturbed. In spite of large differences in the amount of paradoxical sleep during the intersession intervals no differences in learning performances were found among the groups. A tendency toward more intertrial crossings was noted in the paradoxical sleep deprived group at the end of training. It is concluded that storage of information acquired during distributed shuttle-box avoidance is not dependent on the presence of paradoxical sleep immediately following learning. Some possibilities are considered that paradoxical sleep may still be involved in memory storage processes.


Signalling by semaphorin receptors: cell guidance and beyond.
Semaphorins are a large family of secreted or cell-bound signals, known to guide axons in developing nervous tissue. They are expressed in a variety of adult and embryonic tissues and are thought to have a broader spectrum of functions. Recent evidence suggests that semaphorins and their receptors play a key role in the control of cellular interactions, most likely in cell-cell repulsion. A subset of semaphorins interacts with neuropilins - cell-surface molecules lacking a signalling-competent cytoplasmic domain. Another large family of transmembrane molecules, namely plexins, bind specifically to semaphorins. Thus plexins, alone, or in association with neuropilins, behave as fully functional semaphorin receptors. The intracellular responses elicited by plexins are unknown, but their large cytoplasmic moiety, containing the strikingly conserved sex-plexin (SP) domain, is likely to trigger novel signal-transduction pathways.


Hepatopulmonary Syndrome in an Adolescent With Insidious Hypoxia and Small Intrahepatic Portal Venous Shunts: Posttransplant Benefit From Sildenafil.
We report a patient without known preexisting liver disease who presented with hepatopulmonary syndrome (HPS) due to aberrant intrahepatic portal venous development leading to portosystemic shunting. Liver transplantation resulted in resolution of portal hypertension and HPS and sildenafil was safely tolerated in the treatment of persistent fatigue and hypoxemia. Twelve months later, patient has normal allograft function and has returned to normal activity.


Purification of pancreatic phospholipase A2 from human duodenal juice.
Phospholipase A2 (EC 188.8.131.52) was purified from delipidated human duodenal juice by hydrophobic and cation exchange chromatography, followed by molecular sieving on an HPLC column. The resulting enzyme preparation of phospholipase A2 had a molecular weight of 14 kDa, a specific activity of 2000 U/mg protein, and an N-terminal amino acid sequence which was characteristic for human pancreatic phospholipase A2.


The nasal chondroma. 2 case reports and a survey of the literature.
Two cases of nasal chondroma are recorded and the past literature reviewed. The importance is stressed of wide surgical excision for these lesions.


Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome.
To investigate the effect of transcription-modulating drugs, fenofibrate and isotretinoin, on metabolic profile, insulin sensitivity of adipose and muscle tissues and gene expression in a genetic model of insulin resistance syndrome, polydactylous rat strain (PD/Cub). Administration of fenofibrate (100 mg/kg/day), isotretinoin (30 mg/kg/day) or vehicle to adult male PD/Cub rats fed standard laboratory chow for 15 days. Parameters of lipid and carbohydrate metabolism-oral glucose tolerance test, serum concentrations of insulin, triglycerides (TG), free fatty acids (FFA), glycerol, total cholesterol (CH); morphometric variables, in vitro insulin sensitivity of adipose and muscle tissues, catecholamine-stimulated lipolysis and the expression of ApoC-III and Hnf-4 genes in liver. Both experimental groups displayed an increase in adiposity with contrasting effects on TG (lowered by fenofibrate and increased by isotretinoin) and gene expression (no change in fibrate-treated rats and increased expression of ApoC-III and Hnf-4 in isotretinoin-treated group). Fenofibrate-treated rats also showed decreased concentrations of FFA and CH with concomitant decrease of catecholamine-induced lipolysis in adipocytes, but also hyperinsulinemia and the highest insulin/glucose ratio. Isotretinoin increased glycerol concentrations and decreased the insulin sensitivity of peripheral tissues. The PD/Cub rat showed a distinct pharmacogenetic reaction to fenofibrate and isotretinoin administration. Several lines of evidence now implicate specific variant(s) of ApoC-III and/or ApoA-V alleles as responsible for the dyslipidemia observed in this genetic model. The PD/Cub strain may also serve as a pharmacogenetic model for dissection of the retinoid-induced hypertriglyceridemia.


Does cesarean protect against fecal incontinence in primiparous women?
The objective of this study was to identify factors associated with new onset of postpartum fecal incontinence in primiparous women. A population-based study was conducted that surveyed all women delivering between 2002 and 2003 in Oregon. Factors associated with fecal incontinence were identified using logistic regression analysis. A total of 6,152 primiparous women completed the survey 3-6 months postpartum with 2,482 reporting a new onset of fecal incontinence (FI) after childbirth. Vaginal delivery was associated with a greater risk of FI compared to cesarean (odds ratio = 1.45; 95% confidence interval, 1.29 to 1.64). However, vaginal delivery without laceration or instrument assistance did not increase the risk of FI over cesarean. Being overweight (body mass index >/=30 kg/m(2)), pushing for greater than 2 h, and constipation were independently associated with postpartum FI (p < 0.05) regardless of route of delivery. This study provides important data to inform counseling and management of primiparous women.


A dual-view multi-resolution laparoscope for safer and more efficient minimally invasive surgery.
Minimally invasive surgery (MIS) is limited in safety and efficiency by the hand-held nature and narrow fields of view of traditional laparoscopes. A multi-resolution foveated laparoscope (MRFL) was invented to address these concerns. The MRFL is a stationary dual-view imaging device with optical panning and zooming capabilities. It is designed to simultaneously capture and display a zoomed view and supplemental wide view of the surgical field. Optical zooming and panning capabilities facilitate repositioning of the zoomed view without physically moving the system. Additional MRFL features designed to improve safety and efficiency include its snub-nosed endoscope, tool-tip auto tracking, programmable focus profiles, unique selectable display modalities, foot pedal controls, and independently controlled surgeon and assistant displays. An MRFL prototype was constructed to demonstrate and test these features. Testing of the prototype validates its design architecture and confirms the functionality of its features. The current MRFL prototype functions adequately as a proof of concept, but the system features and performance require further improvement to be practical for clinical use.


Intraosseous hemangioma of the talus: a case report.
A 35-year-old female patient presented to us with a lesion in the talus that on AP-roentgenographic view simulated an osteoid osteoma. Final pathology revealed it to be an intraosseous hemangioma. An intraosseous hemangioma at this site is extremely uncommon and has not been previously reported.


Smoked cocaine self-administration in females and voucher incentives for abstinence.
There are three purposes for this study: (1) To extend the laboratory study of heavy smoked cocaine use to women, (2) to assess cocaine withdrawal symptoms and (3) to assess the utility of voucher incentives for achieving and maintaining cocaine and other drug abstinence in female cocaine abusers. Ten non-treatment seeking female cocaine smokers resided inpatient for 4-5 days and could smoke up to 6 doses of cocaine base (50 mg each) twice a day (at 1200 h and again at 1600 h) for 2 consecutive days. During the following 2-week outpatient phase, women were given US $40 in merchandise vouchers if urinalysis indicated lower drug levels from the previous day. Women self-administered 20.4 out of 24 possible doses. Compared to the 1200 session, heart rate and blood pressure, but not subjective effects, were still significantly increased prior to the 1600 session. Nine women completed the outpatient phase, attending 98% of their appointments. Using the One-Half Rule, 56% of urines indicated no new cocaine or other drug use. Although a US $40 voucher incentive for a "clean" urine was not sufficient to eliminate cocaine use, the possibility of earning the voucher was sufficient to maintain nearly perfect attendance.


Structure of the human metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site.
Human metapneumovirus and respiratory syncytial virus cause lower respiratory tract infections. The virus fusion (F) glycoprotein promotes membrane fusion by refolding from a metastable pre-fusion to a stable post-fusion conformation. F is also a major target of the neutralizing antibody response. Here we show that a potently neutralizing anti-human metapneumovirus antibody (DS7) binds a structurally invariant domain of F, revealing a new epitope that could be targeted in vaccine development.


Evaluation of effect of measures taken after a DON outbreak.
In April 1999 an amount of 2600 μg/kg DON was found in a sample breakfast cereals in the Netherlands. This event was the start of a lot of activities, which dealt with the prevention, control, health and consumer aspects of DON in food for human consumption. The Food Inspection Services started a monitoring program to measure DON in cereal products, flour and raw cereals. The National Institute of Public Health and the Environment, another part of the Ministry of Health in the Netherlands, was asked to carry out a risk analysis on DON. This was the basis for the Minister of Health to set an action limit for consumer products. She also informed Brussels and asked for a European limit. The Main Board on Agriculture set out to implement measures to be taken at harvesting, milling and bread baking industry. The Scientific Committee on Food of the EC expressed an opinion on DON in December 1999. Worldwide attention leads to discussion of a DON limit by JECFA in February 2001.In the period may 1999 until march 2002 a number of more than 1700 samples were analysed on DON. These originated from the cereal harvest of the years 1998 until 2001. The results showed a sharp decrease of DON content in samples of harvest 1999 when compared to 1998. This lower level was maintained in the 2000 and 2001 harvests. Apparently the measures taken to control the DON level succeeded to maintain values below the action limits. Despite these activities a smaller outbreak of DON appeared in 2001 in pasta products at a lower extent. This indicated that control should be done systematically, not sporadically, and at a European level, which is made possible since EC has set a limit in July 2000. Analytical results of the measurements are presented, together with the chronological order of the associated activities of national, EU and worldwide bodies on human health control. Special attention is paid to DON in bread, related to the level in flour.


Biotypes and DNA fingerprints of cytotoxigenic Helicobacter pylori from patients with gastritis and peptic ulceration in Italy.
Variations in biotypic and DNA characteristics of 21 strains of Helicobacter pylori from patients in central Italy with histologically defined gastritis and/or peptic ulcers were studied. The strains had the same preformed enzyme biotype but differed in motility and cytotoxigenic activity. The presence or absence of these two characteristics were closely associated in 73% of strains and were used to define three phenotypic subsets. Strains of subset 1 (Mot+ Tox+) were most common (52%) particularly amongst patients with peptic ulceration (64%). H. pylori had unique HaeIII and HindIII ribopatterns but no one ribopattern or single band within a ribopattern was characteristic of any particular phenotypic subset. H. pylori from patients with gastritis were genomically as heterogeneous as those from patients with ulcers. Plasmid DNA was detected in four strains (25%) and although three of these were of the same biotype (phenotypic subset 1), there was no general association apparent between plasmid presence and cytotoxic activity. It was concluded that motility was a useful additional feature for biotyping of H. pylori.


Identification of a region of the H,K-ATPase alpha subunit associated with the beta subunit.
The gastric H,K-ATPase consists of an alpha, beta heterodimer. To determine which part of the alpha subunit is associated with the beta subunit, hog gastric vesicles were trypsinized, which left most of the beta subunit undigested. The vesicles were solubilized with either C12E8 (polyoxyethylene 8 lauryl ester) or Nonidet P-40 and then passed over a wheat germ agglutinin column, which retained the beta subunit. Among the fragments of membrane spanning segments obtained by digestion in the absence of K+, only one peptide fragment of the alpha subunit coeluted with the beta subunit, representing only the M7 and M8 membrane spanning segments of the alpha subunit along with their extracytoplasmic connecting loop. With K+ present during digestion, the fragments at 19-21 kDa and at 9.4 kDa were retained on the column, representing the M7 to C-terminal end and the M5/loop/M6 sector of the enzyme. These results provide biochemical evidence that a region of the alpha subunit containing the M7/loop/M8 sector is bound to the beta subunit under both digestion conditions; but when the C-terminal 180-amino acid sector of the alpha subunit remains intact, as found in the presence of K+, there is an additional retention of the M5/loop/M6 sector of the alpha subunit.


Precise material identification method based on a photon counting technique with correction of the beam hardening effect in X-ray spectra.
The aim of our study is to develop a novel material identification method based on a photon counting technique, in which the incident and penetrating X-ray spectra are analyzed. Dividing a 40 kV X-ray spectra into two energy regions, the corresponding linear attenuation coefficients are derived. We can identify the materials precisely using the relationship between atomic number and linear attenuation coefficient through the correction of the beam hardening effect of the X-ray spectra.


Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study.
Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients. This article describes a method for the quantitative determination of decitabine triphosphate in PBMCs using liquid chromatography coupled to tandem mass spectrometry. The method was applied to ex vivo incubated whole blood samples and samples from three patients receiving prolonged low-dose decitabine treatment. We successfully quantitated decitabine triphosphate in PBMCs. Considerable levels were detected in PBMCs from two patients that responded well to therapy, whereas only low levels were present in a non-responding patient. Moreover, the data show that, in contrast to plasma decitabine, intracellular decitabine triphosphate accumulates during a treatment cycle of nine infusions at a dose of 15 mg/m(2). The results suggest a relationship between decitabine triphosphate levels and response to therapy. Based on the observed accumulation of decitabine triphosphate during a treatment cycle, a less intensive dose scheme could be feasible.


Multilocus sequence identification of Penicillium species in cork bark during plank preparation for the manufacture of stoppers.
Despite several studies reporting Penicillium as one of the most frequent fungal genera in cork planks, the isolates were rarely identified to species level. We conducted a detailed study to identify Penicillium species from the field to the factory environment prior to and after boiling the cork planks. A total of 84 samples were analyzed. Of the 486 Penicillium isolates phenotypically identified, 32 representative or unusual strains were selected for identification by multilocus DNA sequence type. Cork proved to be a rich source of Penicillium biodiversity. A total of 30 taxa were recognized from cork including rarely seen species and 6 phylogenetically unique groups. Spores of some species lodged deep in cork can survive the boiling process. P. glabrum, P. glandicola and P. toxicarium, species with high CFU numbers in the field, are still frequently present in cork after boiling. Other species are killed by the boiling treatment and replaced by Penicillium species originating from the factory environment. Species known to contribute to cork taint were isolated at all stages. Good manufacturing practices are necessary at all stages in the preparation of cork planks to minimize the load of Penicillium species that produce cork taint.


Chromatin dynamics and subnuclear gene positioning for transcriptional regulation.
Plants have been found to exhibit diverse characteristics and functions of chromatin organization, showing both similarities and differences to animals. It is becoming clear how chromatin organization is linked to transcriptional regulation in response to environmental stresses. Regulation of specific chromatin positions in the nuclear space is important for transcription, and the mechanisms that enable such chromatin dynamics are gradually being unveiled. Genes move between subdomains responsible for transcriptional activation or suppression in the subnuclear space in a gene repositioning cycle. We propose a model of localized chromatin interaction in nuclear subdomains, in which the dynamics of local chromatin interactions have a more important impact on the regulation of gene expression than large-scale chromatin organization. In this mini-review, we highlight recent findings on chromatin dynamics, particularly involving transcriptional regulation, and discuss future directions in the study of chromatin organization in plants.


Evaluating Mineral Lattices as Evolutionary Proxies for Metalloprotein Evolution.
Protein coordinated iron-sulfur clusters drive electron flow within metabolic pathways for organisms throughout the tree of life. It is not known how iron-sulfur clusters were first incorporated into proteins. Structural analogies to iron-sulfide minerals present on early Earth, suggest a connection in the evolution of both proteins and minerals. The availability of large protein and mineral crystallographic structure data sets, provides an opportunity to explore co-evolution of proteins and minerals on a large-scale using informatics approaches. However, quantitative comparisons are confounded by the infinite, repeating nature of the mineral lattice, in contrast to metal clusters in proteins, which are finite in size. We address this problem using the Niggli reduction to transform a mineral lattice to a finite, unique structure that when translated reproduces the crystal lattice. Protein and reduced mineral structures were represented as quotient graphs with the edges and nodes corresponding to bonds and atoms, respectively. We developed a graph theory-based method to calculate the maximum common connected edge subgraph (MCCES) between mineral and protein quotient graphs. MCCES can accommodate differences in structural volumes and easily allows additional chemical criteria to be considered when calculating similarity. To account for graph size differences, we use the Tversky similarity index. Using consistent criteria, we found little similarity between putative ancient iron-sulfur protein clusters and iron-sulfur mineral lattices, suggesting these metal sites are not as evolutionarily connected as once thought. We discuss possible evolutionary implications of these findings in addition to suggesting an alternative proxy, mineral surfaces, for better understanding the coevolution of the geosphere and biosphere.


Racial and ethnic disparities in antifibrotic therapy in idiopathic pulmonary fibrosis.
Racial disparities have been documented in care of many respiratory diseases but little is known about the impact of race on the treatment of interstitial lung diseases. The purpose of this study was to determine how race and ethnicity influence treatment of idiopathic pulmonary fibrosis. Adults with idiopathic pulmonary fibrosis (>18 years) were identified using TriNetX database and paired-wised comparisons were performed for antifibrotic treatment among White, Black, Hispanic and Asian patients. Mortality of treated and untreated IPF patients was compared after propensity score matching for age, sex, nicotine dependence, oxygen dependence and predicted FVC. Additional comparisons were performed in subgroups of IPF patients older than 65 years of age and with lower lung function. Of 47,184 IPF patients identified, the majority were White (35,082), followed by Hispanic (6079), Black (5245) and Asian (1221). When subgroups were submitted to matched cohort pair-wise comparisons, anti-fibrotic usage was lower among Black patients compared to White (6.2% vs. 11.4%, p-value <0.0001), Hispanic (10.8% vs. 20.2%, p-value <0.0001) and Asian patients (9.6% vs. 14.7%, p-value = 0.0006). Similar treatment differences were noted in Black individuals older than 65 years and those with lower lung function. Mortality among White patients, but not Hispanic, Black, or Asian patients, was lower in patients on antifibrotic therapy versus not on therapy. This study demonstrated that Black IPF patients had lower antifibrotic use compared to White, Hispanic and Asian patients. Our findings suggest that urgent action is needed to understand the reason why racial disparities exist in the treatment of IPF.


A method for the accurate determination of anti-hapten cytotoxic T lymphocyte precursors: correction for apparent 'anti-self' reactivity.
A method is described for accurately determining the frequency of precursors of hapten specific cytotoxic T cells. The method is based on a standard Poisson analysis of limit dilution cultures, but makes a correction of 'anti-self' reacting clones and for spontaneously arising clones that recognise modified self. These corrections are shown to be especially important when low hapten densities are used, where there may be more than a 10-fold difference between the corrected and uncorrected frequency estimates. Determined levels of antigen specificity and of H-2 restriction are significantly enhanced by application of this method.


Comparison of Ossiculoplasty Using Autograft Ossicle Versus Allograft (Teflon).
Chronic suppurative otitis media in almost any form can disrupt the integrity of ossicular chain. Various materials have been used for ossicular substitution or reconstruction, including both biologic and alloplastic materials. Teflon piston is now the most widely used prosthesis for reconstruction of the ossicular chain in cases of otosclerosis. The oto-surgeons are still confronted with problems of ossicular reconstruction regarding the surgical procedure to be done, type of graft to be selected especially in low and poor socioeconomic population. Thus, there is a need felt to comprehensively and holistically evaluate the outcome of ossiculoplasty using Autograft ossicle versus Allograft ossicle (Teflon). Total 64 patients of chronic suppurative otitis media with no active ear infection and air-bone-gap of more than 15 dB were admitted for surgery and divided into two groups according to material used for ossiculoplasty as group A (Autograft) and group B (Allograft). Patients were evaluated at 3 and 6 months post-operatively using audiogram. In both Group A and B, the average pre-operative AC was 40.62 dB (SD 9.65) and 39.37 (SD 10.53) respectively. In 3 months there was a change of 8.83% from 40.62 dB to 37.03 dB in Group-A (p < 0.109, not statistically significant) and 13.10% change from 39.37 dB to 34.21 dB in Group-B (p < 0.049, statistically significant) whereas at 6 months, air conduction improved by 14.22% in Group-A (p < 0.01, statistically significant) and by 21.81% in Group-B (p < 0.001, highly statistically significant). Post-operatively at 3 months, improved AB gap was 62.5% in Group-A and 68.75% in Group-B patients. Post-operative AB gap at 6 months, improvement was seen in 78.12% in Group-A while it was 81.25% in Group-B patients. Alloplastic Teflon ossicle appears to be a good alternative for ossicular reconstruction where autologous incus is not available or disease precludes its use.


False-negative ultrasound-guided fine-needle aspiration of axillary lymph nodes in breast cancer patients.
The purpose of this study was to clarify the clinicopathological features of patients with false-negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2 mm) group and macrometastasis (>2 mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non-SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. The false-negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false-negative FNAC results.


Mineral density quantitation of the human cortical iliac crest by backscattered electron image analysis: variations with age, sex, and degree of osteoarthritis.
Bone samples from the rim of the iliac crest were obtained at autopsy from 59 patients aged 23 to 75 years, of whom 10 men and 10 women aged 50-75 years had osteoarthritis diagnosed by hand X-rays. An equal number in the same age group and 10 men and 9 women aged less than 50 years were without osteoarthritis. After embedding the bone in PMMA, the blocks were cut, polished, and coated with carbon. The fractions of bone falling within four consecutive bands of signal level were derived from digital backscattered electron imaging. Normal males had more low and medium density bone and normal females more very high density phase tissue proportionately. In both male and female osteoarthritis cases, low and medium fractions were low. The very high density fraction was mainly calcified fibrocartilage; when it was excluded from the calculations, the low, medium, and high phases occurred equally in normal males but increased stepwise in normal females and in osteoarthritis cases of both sexes. The results suggest a lower rate of bone renewal in females than males, and in male osteoarthritis subjects than normal males. An increased proportion of bone of high density would reduce the quality of the bone by increasing its stiffness.


Ca(2+) and Mg(2+) binding to weak sites of TnC C-domain induces exposure of a large hydrophobic surface that leads to loss of TnC from the thin filament.
The C-domain of troponin C, the Ca(2+)-binding subunit of the troponin complex, has two high-affinity sites for Ca(2+) that also bind Mg(2+) (Ca(2+)/Mg(2+) sites), whereas the N-domain has two low-affinity sites for Ca(2+). Two more sites that bind Mg(2+) with very low affinity (K(a)<10(3)M(-1)) have been detected by several laboratories but have not been localized or studied in any detail. Here we investigated the effects of Ca(2+) and Mg(2+) binding to isolated C-domain, focusing primarily on low-affinity sites. Since TnC has no Trp residues, we utilized a mutant with Phe 154 replaced by Trp (F154W/C-domain). As expected from previous reports, the changes in Trp fluorescence revealed different conformations induced by the addition of Ca(2+) or Mg(2+) (Ca(2+)/Mg(2+) sites). Exposure of hydrophobic surfaces of F154W/C-domain was monitored using the fluorescence intensity of bis-anilino naphthalene sulfonic acid. Unlike the changes reported by Trp, the increments in bis-ANS fluorescence were much greater (4.2-fold) when Ca(2+)+Mg(2+) were both present or when Ca(2+) was present at high concentration. Bis-ANS fluorescence increased as a function of [Ca(2+)] in two well-defined steps: one at low [Ca(2+)], consistent with the Ca(2+)/Mg(2+) sites (K(a) approximately 1.5 x 10(6)M(-1)), and one of much lower affinity (K(a) approximately 52.3M(-1)). Controls were performed to rule out artifacts due to aggregation, high ionic strength and formation of the bis-ANS-TnC complex itself. With a low concentration of Ca(2+) (0.6mM) to occupy the Ca(2+)/Mg(2+) sites, a large increase in bis-ANS binding also occurred as Mg(2+) occupied a class of low-affinity sites (K(a) approximately 59 M(-1)). In skinned fibers, a high concentration of Mg(2+) (10-44 mM) caused TnC to dissociate from the thin filament. These data provide new evidence for a class of weak binding sites for divalent cations. They are located in the C-domain, lead to exposure of a large hydrophobic surface, and destabilize the binding of TnC to the regulatory complex even when sites III and IV are occupied.


The errors of our ways: taking account of error in computer-aided drug design to build confidence intervals for our next 25 years.
The future of the advancement as well as the reputation of computer-aided drug design will be guided by a more thorough understanding of the domain of applicability of our methods and the errors and confidence intervals of their results. The implications of error in current force fields applied to drug design are given are given as an example. Even as our science advances and our hardware become increasingly more capable, our software will be perhaps the most important aspect in this realization. Some recommendations for the future are provided. Education of users is essential for proper use and interpretation of computational results in the future.


Constitutive synthesis of polyoma antisense RNA renders cells immune to virus infection.
Mouse fibroblasts were stably transfected with expression plasmids in which sequences of the early region of polyomavirus were inserted both in sense and antisense orientation. The cell lines that synthesize in the antisense orientation, a 1195-bp viral genome fragment covering the Ori, Cap, ATG, and all of the early mRNA splicing sites acquire resistance to viral infection. Smaller fragments covering Ori, Cap, and ATG sites or the splicing sites, as well as fragments cloned in sense orientation, failed to confer cell immunity to polyoma infection. The resistance proved to be directly dependent upon the specific antisense RNA and to be inversely proportional to the multiplicity of infecting polyoma.


Molecular characterization of Thelazia lacrymalis (Nematoda, Spirurida) affecting equids: a tool for vector identification.
Equine thelaziosis caused by the eyeworm Thelazia lacrymalis is a parasitic disease transmitted by muscid flies. Although equine thelaziosis is known to have worldwide distribution, information on the epidemiology and presence of the intermediate hosts of T. lacrymalis is lacking. In the present work, a PCR-RFLP based assay on the first and/or second internal transcribed spacer (ITS1 and ITS2) of ribosomal DNA was developed for the detection of T. lacrymalis DNA in its putative vector(s). The sensitivity of the technique was also assessed. The restriction patterns obtained readily differentiated T. lacrymalis from four species of Musca (Diptera, Muscidae) (i.e. Musca autumnalis, Musca domestica, Musca larvipara and Musca osiris), which are potential vectors of equine eyeworms. The molecular assay presented herein is a useful tool to identify the intermediate host(s) of T. lacrymalis in natural conditions and to study its/their ecology and epidemiology.


Aerobic fitness and the physiological stress response: a critical evaluation.
Aerobically fit persons need less sympathetic activation to perform the same absolute workload than less fit persons. This led to the idea that aerobic fitness might reduce the physiological activation during psychological stress as well. Several experiments showed inconsistent results with regard to this supposed effect of fitness. The comparability of the results is hampered by the differences in operationalization of aerobic fitness and by the confusion of the terms aerobic fitness, training and habitual physical exercise. The expectancy of an effect of fitness on the physiological stress response is based on the assumption that this response resembles the response to exercise. The tenability of this assumption was examined for cardiac, vascular and hormonal responses respectively. It was concluded that the two types of responses only superficially have similarity. So a simple analogy between the stress and the exercise response does not allow a reliable prediction concerning the effect of fitness on the stress response. There are however other reasons to expect an effect. Especially the effect of fitness on adrenoceptor sensitivity suggests that the most important effect of fitness might be found in the vascular part of the stress response. It is argued that the measurement of complete response patterns, instead of isolated parameters, is a prerequisite for progress in this field. Future studies should address the question what the relative contribution of psychological and physiological factors is to the effect of fitness on the physiological stress response.


Population-level use of gynecological health services by female youth with intellectual/developmental disabilities in British Columbia Canada.
There is evidence that female youth with intellectual/developmental disabilities (IDD) experience poorer gynecological care compared to female youth without disabilities. The objective of this study was to obtain baseline data on visits to a health care provider for a gynecological issue for females with IDD and compare that information to the experiences of female youth without IDD. This study is a retrospective cohort study using population-level administrative health data from 2010 to 2019 for females aged 15-24 years, with and without IDD. 6452 female youth with IDD and 637,627 female youth without IDD were identified in the data. Over the ten-year period, 53.77% of youth with IDD and 53.68% of youth without IDD had a visit to a physician for a gynecological issue. However, as females with IDD aged, the number of people seeing a physician for a gynecological issue decreased. In the group aged 20-24 years, 15.25% of females with IDD and 24.47% of females without IDD (p < 0.0001) had a Pap test done at any time; 25.94% of females with IDD had a visit for contraception management and 28.38% of females (p < 0.0001) without IDD had a visit for contraception management. Gynecological care also varied by type of IDD. Females with IDD had a similar number of visits for a gynecological issue as female youth without IDD. However, the reasons for visits and the age at which visits occurred differed between youth with and without IDD. As females with IDD transition into adulthood, gynecological care must be maintained and improved.


Exposure to multiple air pollutant mixtures and the subtypes of hypertensive disorders in pregnancy: A multicenter study.
Hypertensive disorders in pregnancy (HDP) have heterogeneous etiologies. Previous studies have linked individual air pollutants to overall HDP with inconsistent results. Moreover, it has not been explored how exposure to a mixture of multiple air pollutants may affect the risks of the subtypes of the disorders. To investigate the associations of exposure to air pollutant mixture in the 1st and 2nd trimesters of pregnancy with the risks of HDP and its subtypes. Pregnancy data were obtained from the China Labor and Delivery Survey, a nationwide cross-sectional survey in 2015 and 2016. Levels of air pollutants [including fine particulate matter (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2)] in the 1st and 2nd trimesters were estimated based on the model developed by the Institution of Atmospheric Physics, Chinese Academy of Science. Generalized linear mixed models were built to assess the single-exposure effects of air pollutants in early gestation on HDP. The restricted cubic spline function was further applied to assess the potential non-linearity. The weighted quantile sum (WQS) regression was used to investigate the effects of co-exposure to multiple air pollutants. A total of 67,512 pregnancies were included, and 2,834 were HDP cases. The single-effect analysis showed that CO, PM2.5, and SO2 exposure in the 2nd trimester was positively associated with the risks of gestational hypertension (GH), with adjusted odds ratios (aORs) and 95% confidence intervals (CI) of 1.16 (1.04, 1.28), 1.19 (1.04, 1.37), and 1.13 (1.04, 1.22), respectively. The first-trimester O3 exposure was also associated with an increased preeclampsia/eclampsia (PE) risk (aOR = 1.17; 95%CI: 1.02, 1.33). WQS regression confirmed positive associations of air pollutant mixture with HDP subtypes, with PM2.5 as the main contributing pollutant to GH, and CO and O3 as the main pollutants to PE. Exposure to multiple air pollutant mixtures in early pregnancy was associated with increased risks of hypertensive disorders in pregnancy.


Diabetes care program addresses specific needs.
Experienced nurse peer educators are keys to program's success. Hospital-sponsored community program may be a model for others to follow. Program also benefits hospitals by reducing length of stay for diabetic patients.


Unscheduled and out-of-hours care for people in their last year of life: a retrospective cohort analysis of national datasets.
To analyse patterns of use and costs of unscheduled National Health Service (NHS) services for people in the last year of life. Retrospective cohort analysis of national datasets with application of standard UK costings. All people who died in Scotland in 2016 aged 18 or older (N=56 407). Frequency of use of the five unscheduled NHS services in the last 12 months of life by underlying cause of death, patient demographics, Continuous Unscheduled Pathways (CUPs) followed by patients during each care episode, total NHS and per-patient costs. 53 509 patients (94.9%) had at least one contact with an unscheduled care service during their last year of life (472 360 contacts), with 34.2% in the last month of life. By linking patient contacts during each episode of care, we identified 206 841 CUPs, with 133 980 (64.8%) starting out-of-hours. People with cancer were more likely to contact the NHS telephone advice line (63%) (χ2 (4)=1004, p<0.001) or primary care out-of-hours (62%) (χ2 (4)=1924,p<0.001) and have hospital admissions (88%) (χ2 (4)=2644, p<0.001). People with organ failure (79%) contacted the ambulance service most frequently (χ2 (4)=584, p<0.001). Demographic factors associated with more unscheduled care were older age, social deprivation, living in own home and dying of cancer. People dying with organ failure formed the largest group in the cohort and had the highest NHS costs as a group. The cost of providing services in the community was estimated at 3.9% of total unscheduled care costs despite handling most out-of-hours calls. Over 90% of people used NHS unscheduled care in their last year of life. Different underlying causes of death and demographic factors impacted on initial access and subsequent pathways of care. Managing more unscheduled care episodes in the community has the potential to reduce hospital admissions and overall costs.


Virtue rewarded: reinforcement and punishment in an acute psychiatric admission ward.
This study evaluated the naturally occurring behaviour of psychiatric patients in an acute psychiatric setting. Direct behavioural observations were carried out to determine the amount of time patients spent in interaction, with whom they interacted, and the nature of the interaction. Also examined were each respondent group's type and rate of interactive behavior. For much of the time no interactive behaviour was observed to occur, but much of the behaviour exhibited by patients was socially appropriate. When social interactions did occur, both fellow patients and staff tended to reinforce appropriate behaviour. However, nurses reinforced inappropriate crazy behaviour much less than did fellow-patients or non-nursing staff. Treatment implications are discussed.


[The problems with the use of benzodiazepines in elderly patients].
Benzodiazepines (BZD) are widely used to treat anxiety and insomnia in elderly patients. The interest of this prescription is discussed in this article. The discussion is based on the pharmacological properties and adverse effects of BZDs in the elderly. The conclusions are that BZDs should be rarely prescribed in this population; many patients treated by BZDs should be withdrawn and therapeutic strategies, other than BZDs, should be considered to treat anxiety and insomnia in these patients. Problems posed by BZD in the aged patient are both of a pharmacodynamic and pharmacokinetic order. In comparison to young adult users, BZD users among the aged are essentially women; the latter take these medications during important periods in their lives and often have a strong comorbidity, such as cardiovascular or rhumatological problems or even psychiatric problems, such as depression or panic disorders. Aged patients who take BZD at high doses can also consume other drugs, such as alcohol, and often have a psychiatric history. Some important side effects are associated with the use of BZD; essentially concerning falls, and it has been noticed for some years that problems posed by aged car drivers can be enhanced by BZD. It is difficult to know if continual users of BZD really have an advantage over other users. However, instruments, such as an indicator in the form of an algorithm, have been developed to identify the appropriateness of prescribing BZD to elderly patients. It is obvious that it is essential, whenever possible, to have a recourse strategy for cessation, and as much as possible to use BZD with a short half-life that are not oxidised, i.e. essentially BZD that are not metabolised in the strictest sense of the term, such as lorazepam or temazepam. Daily doses must be extremely limited and duration of use should not exceed two or three months in young patients.


Biocatalysis mechanism for p-fluoronitrobenzene degradation in the thermophilic bioelectrocatalysis system: Sequential combination of reduction and oxidation.
To verify the potentially synthetic anodic and cathodic biocatalysis mechanism in bioelectrocatalysis systems (BECSs), a single-chamber thermophilic bioelectrocatalysis system (R3) was operated under strictly anaerobic conditions using the biocathode donated dual-chamber (R1) and bioanode donated dual-chamber (R2) BECSs as controls. Direct bioelectrocatalytic oxidation was found to be infeasible while bioelectrocatalytic reduction was the dominant process for p-Fluoronitrobenzene (p-FNB) removal, with p-FNB removal of 0.188 mM d(-1) in R1 and 0.182 mM d(-1) in R3. Cyclic voltammetry experiments confirmed that defluorination in the BECSs was an oxidative metabolic process catalyzed by bioanodes following the reductive reaction, which explained the 0.034 mM d(-1) defluorination in R3, but negligible defluorination in controls. Taken together, these results revealed a sequentially combined reduction and oxidation mechanism in the thermophilic BECS for p-FNB removal. Moreover, the enrichment of Betaproteobacteria and uniquely selected Bacilli in R3 were probably functional populations for p-FNB degradation.


Dynamic surface tension of micellar solutions in the millisecond and submillisecond time range.
The analysis of the available bubble life times and dead times for the bubble pressure tensiometer BPA-1S shows that dynamic surface tensions can be measured also for surfactant solutions at concentrations many times higher than the corresponding CMC. For the three nonionic surfactants Triton X-100, Triton X-45, and C14EO8 experiments are performed for solutions with a concentration of up to 200 times the CMC (C14EO8). Comparison of the experimental data with micelle kinetics models yields rate constants for the fast micelle dissolution process, which are in a good agreement with values obtained by other experimental methodologies.


On-site sample preparation of trace aromatic amines in environmental waters with monolith-based multichannel in-tip microextraction apparatus followed by HPLC determination.
A novel on-site preparation strategy for the determination of trace aromatic amines (AAs) in environmental waters was developed in the present study. To extract AAs effectively, 4-vinylbenzoic acid was copolymerized with ethylene dimethacrylate (ED)/divinylbenzene (DVB) in a pipette tip to obtain a new monolith-based adsorbent (MBA). The MBAs were employed as the extraction phases of home-made multichannel in-tip microextraction apparatus (ITMA) which was used to perform field sample preparation of AAs in different water samples followed by HPLC/DAD analysis. Due to the abundant functional groups, the prepared MBA displayed satisfying extraction performance for studied AAs. Under the optimized conditions, limits of detection varied from 2.1 to 26 ng/L with good coefficients of determination and precision. The recoveries for real water samples with different fortified concentrations were in the range of 78.1-119%, and the RSD values varied from 0.85 to 11%. In addition, the results achieved with the introduced method were well comparable to that obtained with conventional laboratory sample pretreatment process. Compared with existing approaches, the proposed method exhibits some merits such as s high throughput, good sensitivity and eco-friendliness. Most of important, the MBA/ITMA for on-site preparation avoids the storage and transportation of large volumes of waters, and guarantees the analytical accuracy of studied AAs.


In vitro evolution of an atrazine-degrading population under cyanuric acid selection pressure: evidence for the selective loss of a 47 kb region on the plasmid ADP1 containing the atzA, B and C genes.
The adaptation of microorganisms to pesticide biodegradation relies on the recruitment of catabolic genes by horizontal gene transfer and homologous recombination mediated by insertion sequences (IS). This environment-friendly function is maintained in the degrading population but it has a cost which could diminish its fitness. The loss of genes in the course of evolution being a major mechanism of ecological specialization, we mimicked evolution in vitro by sub-culturing the atrazine-degrading Pseudomonas sp. ADP in a liquid medium containing cyanuric acid as the sole source of nitrogen. After 120 generations, a new population evolved, which replaced the original one. This new population grew faster on cyanuric acid but showed a similar cyanuric acid degrading ability. Plasmid profiles and Southern blot analyses revealed the deletion of a 47 kb region from pADP1 containing the atzABC genes coding for the enzymes that turn atrazine into cyanuric acid. Long PCR and sequencing analyses revealed that this deletion resulted from a homologous recombination between two direct repeats of a 110-bp, identical to ISPps1 of Pseudomonas huttiensis, flanking the deleted 47 kb region. The loss of a region containing three functional genes constitutively expressed thereby constituting a genetic burden under cyanuric acid selection pressure was responsible for the gain in fitness of the new population. It highlights the IS-mediated plasticity of the pesticide-degrading potential and shows that IS not only favours the expansion of the degrading genetic potential thanks to dispersion and duplication events but also contribute to its reduction thanks to deletion events.


Nickel-catalysed chemoselective C-3 alkylation of indoles with alcohols through a borrowing hydrogen method.
An inexpensive, air-stable, isolable nickel catalyst is reported that can perform chemoselective C3-alkylation of indoles with a variety of alcohols following "borrowing hydrogen". A one-pot, cascade C3-alkylation starting from 2-aminophenyl ethyl alcohols, and thus obviating the need for pre-synthesized indoles, further adds to the broad scope of this method. The reaction is radical-mediated, and is significantly different from other examples, often dictated by metal-ligand bifunctionality.


Health-related quality-of-life impact of pembrolizumab versus best supportive care in previously systemically treated patients with advanced hepatocellular carcinoma: KEYNOTE-240.
Health-related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE-240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient-reported outcomes. Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and its HCC supplement (EORTC QLQ-HCC18) electronically at baseline; at weeks 2, 3, 4, 6, 9, 12, and 18; and then every 9 weeks until 1 year or end of treatment, and at the 30-day safety follow-up visit. The HRQoL population included 271 and 127 patients randomly assigned to pembrolizumab and placebo, respectively. From baseline to week 12, changes in both scores were similar between pembrolizumab and placebo; global health status/QoL scores were stable. The proportions of patients who improved, remained stable, or deteriorated across all functional domain and symptom scores were generally similar between pembrolizumab and placebo. Time to deterioration was similar between the 2 arms based on the prespecified analysis of EORTC QLQ-HCC18 domains of abdominal swelling, fatigue, and pain. Pembrolizumab preserved HRQoL during treatment for advanced HCC. Combined with efficacy and safety results from KEYNOTE-240, these findings support a positive benefit/risk profile for pembrolizumab in a second-line treatment setting for patients with HCC who previously received sorafenib.


Electrophysiological and immunogenetic findings in recurrent monosymptomatic-type hypersomnia: a study of two unrelated Italian cases.
MSLT and immunogenetic findings in two unrelated Italian subjects with recurrent monosymptomatic hypersomnia are reported. In both patients MSLT documented a markedly increased daytime sleep propensity during the attacks without augmented REM sleep pressure. Both patients share the same HLA haplotype (HLA-DR1, DQ1) which has been found in Kleine-Levin syndrome. This makes these subtypes of recurrent hypersomnia indistinguishable one from the other, under the immunogenetic profile, but permits differentiation from narcolepsy which is HLA-DR2, DQ1 closely linked.


Contraception with two levonorgestrel rod implants. A 5-year study in the United States and Dominican Republic.
A 5-year trial of a two-rod contraceptive implant, which releases the progestin levonorgestrel (LNG rod), was conducted at four clinics with 594 women. Mean age and weight at admission were 25.5 years and 62.4 kg, respectively. Consent to continue through 5 years was sought and obtained when the 3-year cumulative pregnancy rate proved to be 0.8 per 100. No pregnancies occurred in the fourth or fifth years. The 5-year cumulative pregnancy rate was, therefore, 0.8 per 100 with an annual average pregnancy rate below 2 per 1000 women. Prolonged bleeding/spotting (8.2% of subjects) and irregular bleeding (5.6%) were the most frequently cited medical reasons for removal. Removals for headache (4.7%) and weight change (4.0%) were the next most frequent medical reasons. Between 1% and 2% of subjects during the 5-year trial sought removals for each of the following conditions: mood changes, lower abdominal pain, depression, or pain at the implant site. The mean annual continuation rate during the study was 77 per 100. Use per woman averaged 2.96 years. Mean removal time was 5.9 +/- 0.6 min. These data indicate that, for a 5-year period, the two LNG rod implants are equivalent to the six Norplant capsule implants with respect to safety and efficacy parameters, but permit easier and more rapid implant removal.


Examining the feasibility and utility of an SBAR protocol in long-term care.
Ineffective nurse-physician communication in the nursing home setting adversely affects resident care as well as the work environment for both nurses and physicians. Using a repeated measures design, this quality improvement project evaluated the influence of SBAR (Situation; Background of the change; Assessment or appearance; and Request for action) protocol and training on nurse communication with medical providers, as perceived by nurses and physicians, using a pre-post questionnaire. The majority (87.5%) of nurses respondents found the tool useful to organize information and provide cues on what to communicate to medical providers. Limitations expressed by some nurses included the time to complete the tool, and communication barriers not corrected by the SBAR tool. Project findings, including reported physician satisfaction, support the use of SBAR to address both issues of complete documentation and time constraints.


COVID-19 vaccine decision-making among Black women: A qualitative study.
To understand COVID-19 vaccine decision-making among Black women in the United States. We conducted qualitative interviews with 60 Black women (both African American and first- and second-generation immigrants originating from Africa and the Caribbean) living in the Minneapolis/St. Paul Metropolitan Area. Participants who were highly motivated to get vaccinated described their trust in science and a desire to protect themselves and those around them; while those who delayed vaccination reported doubts about vaccine safety. Many reported being influenced by targeted misinformation including the pervasive vaccine myths related to reproductive health. Historical trauma from unethical biomedical research and experiences of racism were also motivating factors. There were several concerns raised that were specific to ethnic groups. Current public health strategies that are intended to promote COVID vaccination are failing Black communities. Participants highlighted the need for clear and culturally appropriate communication about COVID-19 and the vaccines that is aligned with their communities' values and addresses misinformation. The critical insights we have gained by listening to these communities should be used to develop novel vaccination policy approaches.


Effect of corticosteroid and irradiation on caecal amoebic infection in rats.
Albino rats (Wistar strain) were pretreated with corticosteroid, irradiation or both to study the effect on the outcome of amoebic infection given intracaecally. The number of animals with lesions amongst "treated" groups was not significantly different from that amongst untreated control animals (P greater than 0.05) but amoebic pathology was markedly exacerbated amongst the treated animals. It is thus thought that once the amoebic infection is established, amoebae become better established for penetration in the immuno-depressed host. The study further suggests that corticosteroid therapy could aggravate an otherwise sub-clinical amoebic infection in man.


Enterostomy catheter exchange using new polymer-coated guide wire: technical note.
The exchange of enterostomy feeding catheters may be facilitated by the use of a recently developed hydrophilic polymer guide wire. This has been found especially useful in the insertion of catheters constructed of polyurethane or silastic-type materials.


3D stereophotogrammetric analysis of operative effects after broad median craniectomy in premature sagittal craniosynostosis.
There is ongoing discussion on the diagnostic methods, the need of surgical treatment, and the surgical strategies for premature craniosynostosis. This study examined the operative procedure of a standardized broad median craniectomy, active tilting of the forehead, and bitemporal greenstick fracturing in children with premature sagittal craniosynostosis. To objectively analyze the direct surgical results, we used a 3D stereophotogrammetry scanner, as previously described. A 3D analysis showed a significant increase in the width, cranial index (CI), head and coronal circumferences, intracranial volume, and cranial base width after surgery. Head length was the only parameter that demonstrated a significant decrease postoperatively. Asymmetry and the 30° diagonal difference showed no significant changes. 3D stereophotogrammetry is a reliable and valuable tool with no side effects. It demonstrated that the extended surgical procedure achieves good postoperative results with a reduced length and increased width and, therefore, an improved CI. Additionally, the total intracranial volume was significantly increased after surgery.


Possible significance of anti-heat shock protein (HSP-65) antibodies in autoimmune myasthenia gravis.
Myasthenia gravis (MG) is an autoimmune disorder caused by antibody-mediated attack against skeletal muscle nicotinic acetylcholine receptor (AchR) at neuromuscular junction. A close relationship exists between heat shock proteins (HSPs) and numerous autoimmune diseases. HSPs are over expressed to protect the host against various insults. Antibodies to HSP-65 (IgG, IgA, IgM) are evaluated in 40 MG sera by ELISA. About 80% of MG cases showed anti-HSP antibodies (62.5% IgG, 55% IgA, 40% IgM). The result suggests that, expression of HSP-65 increases in MG and most individuals produce antibodies to it. These antibodies might play a significant role in the pathogenesis of MG.


Does the diagnosis of detrusor overactivity affect the long-term prognosis of patients treated with a retropubic midurethral sling?
There are few long-term studies on the midurethral sling (MUS) procedure in patients with preoperative detrusor overactivity (DO) and there is debate regarding the usefulness of preoperative cystometry. This study was designed to provide long-term efficacy and safety data for the Advantage MUS and to compare the outcomes in patients with pure urodynamic stress incontinence (USI) with the outcomes in patients with mixed USI and DO. This was a retrospective consecutive case series study of 100 patients with USI (USI-only group) matched to a consecutive group of a further 100 patients with preoperative USI and DO (mixed group) treated with a retropubic MUS. Outcomes were assessed using the King's Health Questionnaire and Patient Global Impression of Improvement questionnaire. After a mean follow up of 6 years more patients in the USI-only group described themselves as "very much better" or "much better" (86 % USI-only group vs. 57 % mixed group; p = 0.007). Quality of life was improved at 6 years from baseline in both groups. Patients in the mixed group were more likely to complain of urgency (69 % vs. 42 %; p = 0.0007) which was more likely to be severe (34 % vs. 10 %; p = 0.004). A repeat MUS procedure was needed in 1 % of patients and 0.6 % needed surgical removal of the MUS for persistent troublesome pain. This study suggests that the preoperative diagnosis of DO affects the long-term patient-perceived outcome of the MUS procedure. However, most patients have significant long-term improvement in quality of life.


An outbreak of SARS-CoV-2 infections among people living with HIV and its successful containment-Taiwan, May to August 2021.
In Taiwan, 14,308 locally acquired COVID-19 cases among customers and employees in Sexy Tea shops were the first cases from May 9-August 28, 2021 (weeks 19-34). Nine weeks after the community spread of COVID-19 began, the proportion of people living with HIV (PLHIV) among the COVID-19 patients peaked at 35.7%, affecting 192 HIV patients, while the prevalence of HIV infection was 0.15%. In addition to a nationwide Level 3 epidemic alert, the Taiwan Centers for Disease Control (Taiwan CDC) launched four strategies to contain this outbreak among PLHIV in this prevaccine era, including improving the quality of contact tracing, delivering health information via peer navigators, expanding SARS-CoV-2 screening and encouraging vaccination, and addressing hesitancy. The outbreak of COVID-19 related to Alpha strain among PLHIV in 2021 ceased four weeks after peaking and lasted eight weeks.


Mixing behavior of the rhombic micromixers over a wide Reynolds number range using Taguchi method and 3D numerical simulations.
A planar micromixer with rhombic microchannels and a converging-diverging element has been systematically investigated by the Taguchi method, CFD-ACE simulations and experiments. To reduce the footprint and extend the operation range of Reynolds number, Taguchi method was used to numerically study the performance of the micromixer in a L(9) orthogonal array. Mixing efficiency is prominently influenced by geometrical parameters and Reynolds number (Re). The four factors in a L(9) orthogonal array are number of rhombi, turning angle, width of the rhombic channel and width of the throat. The degree of sensitivity by Taguchi method can be ranked as: Number of rhombi > Width of the rhombic channel > Width of the throat > Turning angle of the rhombic channel. Increasing the number of rhombi, reducing the width of the rhombic channel and throat and lowering the turning angle resulted in better fluid mixing efficiency. The optimal design of the micromixer in simulations indicates over 90% mixing efficiency at both Re > or = 80 and Re < or = 0.1. Experimental results in the optimal simulations are consistent with the simulated one. This planar rhombic micromixer has simplified the complex fabrication process of the multi-layer or three-dimensional micromixers and improved the performance of a previous rhombic micromixer at a reduced footprint and lower Re.


A portable smartphone-based colorimetric sensor that utilizes dual amplification for the on-site detection of airborne bacteria.
Over the past few years, infections caused by airborne pathogens have spread worldwide, infecting several people and becoming an increasingly severe threat to public health. Therefore, there is an urgent need for developing airborne pathogen monitoring technology for use in confined environments to enable epidemic prevention. In this study, we designed a colorimetry-based bacterial detection platform that uses a clustered regularly interspaced short palindromic repeat-associated protein 12a system to amplify signals and a urease enzyme to induce color changes. Furthermore, we have developed a smartphone application that can distinguish colors under different illumination conditions based on the HSV model and detect three types of disease-causing bacteria. Even synthetic oligomers of a few picomoles of concentration and genomic DNA of airborne bacteria smaller than several nanograms can be detected with the naked eye and using color analysis systems. Furthermore, in the air capture model system, the bacterial sample generated approximately a 2-fold signal difference compared with that in the control group. This colorimetric detection method can be widely applied for public safety because it is easy to use and does not require complex equipment.


The structure of the lung of the newborn marsupial bandicoot, Isoodon macrourus.
In bandicoots, implantation takes place 9.5 days after mating and birth occurs 3 days later. It is therefore of interest to examine the lungs of newborn marsupials to ascertain the stage of lung development with respect to other organs and other mammals in view of the short period of time allowed for maturation of lung tissue. The newborn bandicoot lung is composed of a primitive system of branching airways which terminate in large blind sacs; alveolar ducts or alveoli are not present. The terminating sacs, which are delineated by thick connective-tissue septae, have a highly vascularised internal lining. Thin squamous cells and numerous type-II "surfactant"-secreting cells constitute the air interface of the sac. Corticosteroids influence the development of the eutherian fetal lung by accelerating pulmonary maturation and increasing the synthesis of surfactant. Since recent evidence indicates that the adrenal of the bandicoot is active at, or before birth, it is possible that this organ also plays an important role in preparing the lungs of the marsupial for extra-uterine life in the pouch.


Septic arthritis of the hip with Propionibacterium avidum bacteremia after intraarticular treatment for hip osteoarthritis.
Propionibacterium avidum is a Gram-positive, nonsporulating, facultative anaerobe that has a low level of virulence and is rarely pathogenic. This ubiquitous inhabitant of the sebaceous glands and hair follicles can cause acne vulgaris. Very rarely, P. avidum causes systemic infections after invasive procedures, most notably in immunocompromised patients. Two cases of sacroiliitis due to P. avidum have been reported. We report a case of P. avidum arthritis of the hip with severe sepsis that developed in a 78-year-old woman after intraarticular glucocorticoid treatment for hip osteoarthritis. We are unaware of previous reports of P. avidum hip arthritis.


Three-dimensional power Doppler study of endometrial and subendometrial microvascularization in women with intrauterine device-induced menorrhagia.
To evaluate endometrial and subendometrial microvascularization, using three-dimensional (3D) power Doppler ultrasound, in women with intrauterine device (IUD)-induced menorrhagia; and whether those potential findings could predict the risk of bleeding before IUD insertion. Prospective clinical trial. University teaching hospital. One hundred twenty women, who requested the insertion of a copper IUD for contraception. Endometrial thickness and volume, uterine artery pulsatility index and resistance index, and endometrial and subendometrial 3D power Doppler vascularization index, flow index, and vascularization flow index were measured twice: immediately before and 3 months after IUD insertion. Doppler indices before and after IUD insertion. Before IUD insertion, no significant difference was detected in the clinical characteristics, endometrial thickness and volume, and Doppler indices between women who had IUD-induced menorrhagia (n = 47) and those without menorrhagia (n = 73). However, after IUD insertion, there was a significant increase in the endometrial and subendometrial vascularization index, flow index, and vascularization flow index in women with menorrhagia, whereas other parameters remained not significantly different between the two groups. Endometrial and subendometrial microvascularization increases in women with IUD-induced menorrhagia; however, this finding has no predictive value before IUD insertion.


Application of core-shell technology for determination of retinol and alpha-tocopherol in breast milk.
Breast milk is a main source of fat-soluble vitamins for newborns and it is needful to monitor the nutritional status prior to its application. In this work a novel, high-throughput and low-cost method for monitoring of retinol and alpha-tocopherol in breast milk was developed, validated and compared with reference method using monolithic column. For this purpose five various porous shell and monolithic columns were tested on the basis of relationship between HETP and linear mobile phase velocity, analysis time and consumption of solvents. Finally the core-shell analytical column Kinetex C18 (2.6 μm, 100 Å, 100×4.6 mm) was chosen as the best and optimal values of flow rate, injection volume and temperature of analysis were established. The detection of retinol and alpha-tocopherol was carried out at 325 and 295 nm, respectively by diode array detector. The LOD 0.004 μmol/L and 0.078 μmol/L, the LOQ 0.012 μmol/L and 0.182 μmol/L for retinol and alpha-tocopherol, respectively were calculated. The validation data showed good linearity, repeatability of retention time with RSD 0.22% and 0.12%, repeatability of peak area with RSD 6.94% and 1.75%, recovery 114.1-116.3% and 99.0-108.6% for retinol and alpha-tocopherol, respectively. Moreover, the newly developed method substantially decreased the solvent consumption by about 263 mL per 100 samples with the total time of analysis 1.75 min in comparison with analysis time 1.80 of the reference method.


The impact of time length to Boolean remission for tight disease activity control after acquisition in rheumatoid arthritis patients.
Clinical importance of time length from initiation under treat-to-target (T2T) strategy to acquisition of clinical remission (TL) in treating patients with rheumatoid arthritis (RA) on disease activity control, daily activities, and quality of life maintenance was investigated. In patients who achieved Boolean remission once or more, relationship between TL and patients' background data at initiation, and relationship between TL and mean simplified disease activity score (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) score, pain score with visual analog scale (PS-VAS), Sharp/van der Heijde Score (SHS) and quality of life score (QOLS) at the first remission and thereafter were evaluated statistically. Patients were divided into two groups whether TL was within 6 months or longer (G ≤ 6 and G > 6). Change of the parameters and Boolean remission rate (BRR) after the first remission between the two groups were compared statistically. In 465 patients, TL correlated significantly with the SDAI score, the HAQ score, PS-VAS, SHS, and the QOLS after the remission. The SDAI score and the BRR after the remission were significantly better in the G ≤ 6 than in the G > 6. TL is an important key to guarantee good and stable clinical course in treating under T2T.


The Pediatric Personal Care Allocation Model for Home Care (PCAM): A Personal Care Case-Mix Model for Children Facing Special Health Care Challenges.
State Medicaid programs in the United States provide services to children with special health care challenges through the Early Prevention, Screening, Diagnostic, and Treatment program. One element of the services provided is Medicaid Personal Care Services (PCS), which are intended to correct or ameliorate any functional impairments faced by a child or youth (C/Y) in the community. Previous research indicates that considerable variation in the allocation of PCS depends on the assessor. A case-mix model is developed that might make the distribution of such services more uniform and equitable. The sample in this research includes 2708 C/Y aged 4 to 20 who were receiving PCS in Texas in 2008. A case-mix model was developed that groups sample members into 33 categories based on the number of hours of PCS authorized by an assessor. The Pediatric Personal Care Allocation Model (PCAM) explains 27% of the variance in the allocation of PCS hours. The implementation of the PCAM should provide guidance to assist in ensuring that C/Y facing similar functional challenges receive similar levels of PCS. However, implementation of any case-mix model is only a first step in moving to a prospective payment system for PCS.


Quantitative comparative mutagenesis in bacteria, mammalian cells, and animal-mediated assays. A convenient way of estimating genotoxic activity in vivo?
The accumulation of environmental compounds which exhibit genotoxic properties in short-term assays and the increasing lag of time for obtaining confirmation or not in long-term animal mutagenicity and carcinogenicity tests, makes it necessary to develop alternative, rapid methodologies for estimating genotoxic activity in vivo. In the experimental approach used here, it was assumed that the genotoxic activity of foreign compounds in animals, and ultimately humans, is determined among others by exposure level, organ distribution of (DNA) dose, and genotoxic potency per unit of dose, and that knowledge about these 3 parameters may allow to rapidly determine the expected degree of genotoxicity in various organs of exposed animals. In view of the high degree of qualitative correlation between mutagenic activity of chemicals in bacteria and in cultured mammalian cells, and their mutagenic and carcinogenic properties in animals, and in order to be able to distinguish whether mutagenic potency differences were due to differences in (DNA) dose rather than other physiological factors, the results of mutagenicity tests obtained in the present experiments using bacteria and mammalian cells were compared on the basis of DNA dose rather than exposure concentrations, with the following questions in mind: Is there an absolute or a relative correlation between the mutagenic potencies of various ethylating agents in bacteria (E. coli K12) and in mammalian cells (V79 Chinese hamster) after treatment in standardized experiments, and can specific DNA adducts be made responsible for mutagenicity? Is the order of mutagenic potency of various ethylating agents observed in bacteria in vitro representative of the ranking of mutagenic potency found in vivo? Since the answer to this last question was negative, a further question addressed to was whether short-term in vivo assays could be developed for a rapid determination of the presence (and persistence) of genotoxic factors in various organs of mice treated with chemicals. In quantitative comparative mutagenesis experiments using E. coli K12 and Chinese hamster cells treated under standardized conditions in vitro with 5 ethylating agents, there was no indication of an absolute correlation between the number of induced mutants per unit of dose in the bacteria and the mammalian cells. The ranking of mutagenic potency was, however, identical in bacteria and mammalian cells, namely, ENNG greater than ENU greater than or equal to DES greater than DEN congruent to EMS, the mutagenic activity of DEN being dependent on the presence of mammalian liver preparations.(ABSTRACT TRUNCATED AT 400 WORDS)


Spina cortica and Tapetum spinosus, two new microstructures of flight feathers: description, function and distribution in modern birds.
The importance of feathers for the avian group has made them one of the most studied epidermal structures both from the morphological and evolutionary point of view. Surprisingly, our observations by Scanning Electron Microscopy detected the presence of two structures widely distributed within different avian groups and not yet described. In this paper we describe these two new structures (Spina cortica and Tapetum spinosus) and map their distribution within modern birds. The S. cortica is a thorn-like microstructure that grows on the barb cortex and the T. spinosus is the assemblage of these thorns. The distribution of these new structures among birds and their morphological diversity could be of great interest to taxonomists and evolutionary biologists interested in the origin of bird flight.


Cytotoxic tirucallane C26 triterpenoids from the stem barks of Aphanamixis grandifolia.
Five tirucallane type C(26) triterpenoids, accompanied by two known compounds, 3α-hydroxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone and 3-oxo-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, were isolated from the stem barks of Aphanamixis grandifolia. Their structures were established mainly by means of a combination of 1D and 2D NMR spectroscopic and mass spectrometry techniques as 3α-hydroxyl-21α-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, 3α-hydroxy-21β-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, 3-oxo-21α-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, 3-oxo-21β-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, and 3-oxo-21α-ethoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone. All isolates were in vitro evaluated for their cytotoxic activities against five tumor cell lines (MCF-7, HeLa, HepG2, SGC-7901 and BGC-823).


Self-medication practices among undergraduate nursing and midwifery students in Australia: a cross-sectional study.
Self-medication is a global phenomenon and a major form of self-care. To explore the self-medication practices of Australian nursing and midwifery students. An online questionnaire that examined the prevalence of self-medication, reasons for self-medication, medications consumed and medication knowledge was distributed to student nurses and midwives at one university in Victoria, Australia. Data were collected between February and May 2014. Self-medication practices were reported in 91.7% (n = 110) of students. Students reported the main reason for self-medication was to play an active role in their health. The incidence of stress was high (n = 82, 74.5%), along with back pain (n = 84, 76.4%) and nearly half the students (n = 46, 42.2%) reported using antibiotics that were prescribed for a previous health problem. Self-medication practices were common in this student cohort and some results give rise to concern for the general wellbeing of our future nursing and midwifery workforce.


Effects of idebenone and related compounds on respiratory activities of brain mitochondria, and on lipid peroxidation of their membranes.
The oxidation of succinate and NADH in a ubiquinone-depleted canine brain mitochondrial preparation was restored by a low molecular weight benzoquinone, idebenone. Idebenone inhibited NADH(NADPH)/ADP-Fe3+-dependent lipid peroxidation in canine brain mitochondria and protected against the resulting inactivation of NADH-cytochrome c reductase activity. Idebenone did not affect the activities of succinate oxidase in canine and rat brain mitochondria but suppressed the oxygen consumption in NADH oxidation. This suppression might be related to the inhibition of lipid peroxidation. These results suggest that idebenone functions as an electron carrier in the respiratory chains of brain mitochondria and as an antioxidant against membrane damage caused by lipid peroxidation in brain mitochondria.


Comparison of Goldmann applanation and dynamic contour tonometry before and after cataract surgery.
To validate changes in intraocular pressure (IOP) after phacoemulsification with intraocular lens (IOL) implantation without pressure-lowering surgery in previously unoperated eyes of normal and glaucoma patients. University Eye Clinic, Otto-von-Guericke-University, Magdeburg, Germany. Cohort study. The IOP in both eyes of patients was determined by Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) 1 to 2 days before and after uneventful unilateral surgery. Central corneal thickness was used to correct raw GAT readings. Of the 50 patients having unilateral phacoemulsification, 29 had had cataract extraction in the contralateral eye. The mean baseline IOP was 17.4 ± 4.4 mm Hg (GAT) and 16.6 ± 2.9 mm Hg (DCT). Postoperatively, the GAT IOP decreased to 16.4 ± 6.5 mm Hg and the DCT IOP increased slightly to 17.1 ± 4.1 mm Hg. The mean tonometer difference (ΔIOP = GAT - DCT) amounted to ΔIOP(pre) = +0.75 ± 2.69 mm Hg in phakic eyes and ΔIOP(post) = -0.70 ± 3.76 mm Hg in pseudophakic eyes (P=.0011). Consistent results were found in pairs of phakic eyes and pseudophakic eyes (mean IOP 18.0 ± 4.8 mm Hg [GAT] and 17.0 ± 3.3 mm Hg [DCT]). In fellow eyes, the mean GAT reading was 13.4 ± 4.4 mm Hg and the mean DCT value, 14.8 ± 2.4 mm Hg. ΔIOP(phakic) was +1.04 ± 2.75 mm Hg and ΔIOP(pseudophakic) was -1.48 ± 2.78 mm Hg (P=.00000021). The GAT IOP readings in pseudophakic eyes seemed to be falsely low. Hence, special attention in the screening, diagnosis, and management of glaucoma is necessary.


Postural costs of performing cognitive tasks in non-coincident reference frames.
Dual-task interactions in posture and cognitive tasks have been explained as a competition for spatial processing structures or as interference in the online sensorimotor adjustments required for sensory integration. Going beyond these general terms accounts, we propose that interference between spatial and temporal operations in posture-cognition arises at least partly from the need to share a common behavioral context, such as a spatial frame of reference. Using immersive visualization and motion-tracking techniques, we manipulated the spatial reference frames for a standing task and a conjunction visual search task into or out of coincidence. Aside from performance trade-offs due to task-load manipulations, performing visual search in a non-coincident reference frame led to cognitive task and postural task performance decrements (Experiment 1). Postural dual-task decrements were also observed when visual search was split between coincident and non-coincident frames and both frame conditions rendered identical in visual information relevant to posture control (Experiment 2). We concluded that the postural control costs observed for posture-cognition dual-tasking may in part reflect costs of keeping tasks' reference frames in register.


Osteoporosis: underrated, underdiagnosed and undertreated.
Osteoporosis is: (1) Underrated. Currently costs about 7 billion dollars annually in Australia. Has high morbidity and 2-3-fold increase in risk of death after any major osteoporotic fracture. Genetic factors contribute highly to risk, modified by lifestyle and hormonal factors. (2) Underdiagnosed. Bone density is a good predictor of subsequent risk. Anyone with a low-trauma fracture has osteoporosis unless proven otherwise. Every individual with a low trauma fracture should be investigated for exclusion of underlying osteoporosis and considered for effective treatment to reduce future fracture risk. More than 75% of women and about 90% of men with a high likelihood of osteoporosis are not investigated. (3) Undertreated. More than 75% of those affected are not treated. Effective treatments (eg, hormone replacement therapy, selective oestrogen receptor modifiers and bisphosphonates) reduce fracture risk by 30%-60%. Simple measures like vitamin D and calcium supplementation and use of hip protectors can reduce hip fractures, particularly in institutionalised and housebound elderly people