Low-cost portable bioluminescence detector based on silicon photomultiplier for on-site colony detection.
A low-cost, portable bioluminescence detector based on a silicon photomultiplier (SiPM) was developed for on-site colony detection, the main components of which are a low-noise photoelectric signal detection and processing circuit, power management module, and high-performance embedded microcontroller subsystem with peripheral circuits. Balanced chopper modulation and lock-in amplification techniques were adopted to improve the signal-to-noise ratio, and a zero-adjustment technique was used to eliminate the dark current of the SiPM to expand the dynamic range. Using this bioluminescence detector, adenosine triphosphate could be determined in the range of 3.6 × 10-6 to 3.6 × 10-11 mol/L, and bacterial colonies could be determined in the range of 1.0 × 103 to 1.0 × 109 CFU/mL, with a limit of quantitation of 1.0 × 103 CFU/mL. Satisfactory recoveries and precision were obtained. Actual samples were accurately tested and the data were verified by comparison with those from the national standard method. The manufacturing cost of the bioluminescence detector was only $30, which is only approximately 1% of the price of current commercial instruments. This study provides a tool for rapid on-site detection of bacterial colonies, as well as a new concept for the development of low-cost portable detection equipment.


Defective oocytes are not a common cause of unexplained infertility as determined by evaluation of sharing oocytes between infertile donors and recipients.
To determine if defective oocytes or sperm may be a common etiologic factor in unexplained infertility. A retrospective comparison of fertilization rates and pregnancy rates from infertile donors with unexplained infertility trying to conceive with in vitro fertilization-embryo transfer (IVF-ET) and their respective recipients, who shared the other half of the oocytes with the recipient's male partner for financial compensation was performed. Pregnancy rates from donors and recipients were also compared to other donor recipient pairs sharing oocytes from infertile donors with tubal or male factor or financially-compensated donors providing oocytes to two recipients. Pregnancy rates from infertile donors with unexplained infertility were comparable not only to their respective recipients but to other donor/recipient pairs that received oocytes from donors with tubal or male factor or financially-compensated donors. Fertilization rates were somewhat reduced in the infertile donors. Abnormal embryos resulting from an oocyte or sperm defect do not appear to be a common cause of unexplained infertility. The possibility does exist that sperm may be an etiologic factor in reduced fertilization potential, which not only could be obviated by conventional oocyte insemination, but could be further improved by intracytoplasmic sperm injection (ICSI).


Remark on models for amplification of asymmetry.
There exists a number of evolutionary models in which a tiny asymmetry in the size of several subpopulations is amplified. In the present paper a counterexample is given based on equally justifiable starting conditions. The existence of similar models leading to contradictory results clearly demonstrates the highly hypothetic nature and questionable value of conclusions drawn from 'by chance' selection models.


Biomimetic mineralization of novel silane crosslinked collagen.
Studies on the mechanisms of mineralization of connective tissues, have gained momentum in the recent past. In the present study, Biomimetic mineralization of modified fish scale collagen in vitro is reported. The fish scale collagen was crosslinked with 3-Aminopropyl triethoxysilane and the crosslinked collagen (FCSi) was characterized using conventional methods. The biomimetic mineralization capacity of FCSi was evaluated in SBF solution for 7 days. Formation of hydroxyapatite crystals on the matrix in vitro has been confirmed by FTIR, XRD and SEM-EDAX techniques. The FCSi may be used as a scaffold in bone tissue engineering and as an osteoinductive material in experimental animal models before applying clinically.


Striatal indirect pathway mediates exploration via collicular competition.
The ability to suppress actions that lead to a negative outcome and explore alternative actions is necessary for optimal decision making. Although the basal ganglia have been implicated in these processes1-5, the circuit mechanisms underlying action selection and exploration remain unclear. Here, using a simple lateralized licking task, we show that indirect striatal projection neurons (iSPN) in the basal ganglia contribute to these processes through modulation of the superior colliculus (SC). Optogenetic activation of iSPNs suppresses contraversive licking and promotes ipsiversive licking. Activity in lateral superior colliculus (lSC), a region downstream of the basal ganglia, is necessary for task performance and predicts lick direction. Furthermore, iSPN activation suppresses ipsilateral lSC, but surprisingly excites contralateral lSC, explaining the emergence of ipsiversive licking. Optogenetic inactivation reveals inter-collicular competition whereby each hemisphere of the superior colliculus inhibits the other, thus allowing the indirect pathway to disinhibit the contralateral lSC and trigger licking. Finally, inactivating iSPNs impairs suppression of devalued but previously rewarded licking and reduces exploratory licking. Our results reveal that iSPNs engage the competitive interaction between lSC hemispheres to trigger a motor action and suggest a general circuit mechanism for exploration during action selection.


Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases.
Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results.


Report from the GHPP-BloodTrain inspection workshop in Harare the 20th to the 24th of May 2019.
During the training workshop on Inspection of Blood Establishments, which was hosted by the PEI GHPP BloodTrain in Harare from the 20th to the 24th of May 2019, participants from the National Regulatory Authorities from seven Sub-Sahara African countries presented their current experiences related to regulation and inspection of blood establishments in their respective countries. While in all seven countries regulation and inspection of conventional medicinal products manufacturer is performed, the regulatory situation of blood and blood components as well as inspection of blood establishments is still heterogeneous.


Magnetic resonance tomography of the knee joint.
To compare the diagnostic performance of magnetic resonance imaging (MRI) in terms of sensitivity and specificity using a field strength of <1.0 T (T) versus ≥1.5 T for diagnosing or ruling out knee injuries or knee pathologies. The systematic literature research revealed more than 10,000 references, of which 1598 abstracts were reviewed and 87 full-text articles were retrieved. The further selection process resulted in the inclusion of four systematic reviews and six primary studies. No differences could be identified in the diagnostic performance of low- versus high-field MRI for the detection or exclusion of meniscal or cruciate ligament tears. Regarding the detection or grading of cartilage defects and osteoarthritis of the knee, the existing evidence suggests that high-field MRI is tolerably specific but not very sensitive, while there is literally no evidence for low-field MRI because only a few studies with small sample sizes and equivocal findings have been performed. We can recommend the use of low-field strength MRI systems in suspected meniscal or cruciate ligament injuries. This does, however, not apply to the diagnosis and grading of knee cartilage defects and osteoarthritis because of insufficient evidence.


Population dynamics of mites in slow-release sachets used in biological control: a new study methodology.
Predatory mite species (Acari: Phytoseiidae) are essential tools in the biological control of greenhouses pests. The natural enemies can be released directly into a crop. A better, partly preventive system is to place slow-release sachets on the plants. Inside such sachets is a factitious prey's food substrate-which also acts as refuge-and the predator. The objective of this study was to develop a new methodology to evaluate the population dynamics of this sachet system, based on the factitious prey Carpoglyphus lactis and the predatory mite Amblyseius swirskii. Through two tests carried out under laboratory conditions, the sachets were first compared to the traditional extraction method that uses Berlese-Tullgren funnels and an extraction method using flotation in hexane. The latter method proved more effective at sampling the motile states (larvae, nymphs, and adults), both for the predatory species and for the factitious prey, extracting up to 3.7 × more mites than the Berlese-Tullgren funnel. Second, the population dynamics of both mite species was studied in a laboratory test, both inside and outside the sachets. In this way, a positive correlation was demonstrated between the number of predatory mites and the number of prey mites inside the sachets. Conversely, no correlation was found between the interior population of predatory mites and the number that venture outside. We can conclude that hexane extraction is very useful both in quality control of predatory mites and in studying how the sachets behave when faced with various factors.


Damage control articular surgery: Maintaining chondrocyte health and minimising iatrogenic injury.
Articular cartilage has limited intrinsic regenerative potential. The maintenance of healthy articular cartilage is essential to prevent joint degeneration and the morbidity associated with arthritis. In this review, we outline the structure and function of healthy articular cartilage. We summarise some of the recent literature outlining the influence of surgical factors on chondrocyte health. These factors include mechanical injury from instrumentation and drilling, drying, and the influence of irrigation fluids, antimicrobial solutions and local anaesthetics. We demonstrate that there is scope for improving cartilage viability at the time of surgery if simple chondroprotective measures are routinely adopted.


The radiologic evaluation of chest pain in the athlete.
Chest pain in the athlete may arise from any one of a number of diverse etiologies. Many of these entities are discussed using an organ system approach. The pathophysiology and clinical characteristics of these processes are described and imaging studies that may aid in establishing their diagnosis are discussed.


[Long latency auditory evoked potentials: value of multichannel analysis and of high-resolution graphic mapping].
Auditory Evoked Potentials maps (AEP) were computed from 32 simultaneously recorded channels over both hemispheres using a linear interpolation algorithm. Reference electrode was extracephalic. Stimulus was a 781 Hz tone (intensity 70 dB HL, duration 256 msec). Average AEP were from 128 responses to randomly delivered stimuli. Direct current and frequencies over 50 Hz were removed by means of a digital filter (FFT). Results from 15 subjects showed before 120 msec a symmetrical response of AEP at vertex with left ear, right ear or binaural stimulation. Between 120 and 170 msec, maps of evoked responses were asymmetrical showing greater potentials over temporal areas contralateral to the stimulated ear.


Fracture of the penis with associated laceration of the urethra.
Two patients with rupture of the urethra secondary to sexual trauma are described. Our results with the surgical treatment of such injuries are reported and the potential etiologies are postulated. One patient had an excellent result, while the other had a residual urethral stricture.


Effect of magnesium infusion on calcium handling in the rat kidney.
Anaesthesized rats were infused with 100 microliters min-1 of 0.9% saline or saline containing 2 or 4 mmol l-1 of magnesium chloride and renal function was studied. Magnesium had no effect on urine flow rate, excretion of sodium or potassium, or glomerular filtration rate (GFR). Infusion of either dose of magnesium increased calcium excretion and calcium concentration in the urine. The increased urinary calcium excretion is due to a decrease in tubular reabsorption of calcium.


Electroconvulsive therapy in patients with diagnoses other than major depression and/or difficult characteristics: a combined psychiatric-anesthesiological approach based on a retrospective chart analysis.
Though electroconvulsive therapy (ECT) requires a close cooperation between anesthesiology and psychiatry, literature lacks of approaches that consider both disciplines in parallel. Special problems might be posed by patients with complicated features or ECT-indications other than treatment-refractory depression (TRD). Considering these patients there is a particular paucity of data, especially regarding anesthesiological aspects. Therefore, we sought (1) to discuss special issues of the peri-interventional management of non-TRD-cases from a combined psychiatric-anesthesiological point of view and (2) to assess the efficacy of ECT in the classical indication of TRD as compared to cases undergoing ECT for other indications or under difficult conditions (non-TRD) by means of Clinical Global Impression-Improvement (CGI-I) scale scores. A retrospective chart analysis of patients treated with ECT between the years 2009 and 2011 at the University of Ulm, Department of Psychiatry, was conducted. Special anesthesiological efforts were necessary in cohort non-TRD. There was no difference in the clinical outcome between cohort non-TRD (n=7) and TRD (n=22) with a median CGI-I score of 2 ("much improved") in both groups. Close cooperation between psychiatry and anesthesiology is indispensable in non-TRD patients. Our results provide preliminary evidence that ECT is equally effective in the standard indication of TRD compared to other indications.


Outcome measures for airway clearance techniques in children with chronic obstructive lung diseases: a systematic review.
Airway clearance techniques (ACTs) are an important aspect of the treatment of children with chronic obstructive lung diseases. Unfortunately, a sound evidence base is lacking and airway clearance strategies are largely based on clinical expertise. One of the reasons for the limited evidence is the lack of appropriate outcome measures specifically related to the effectiveness of ACTs. This review discusses all outcome measures applied in previous research in the pediatric population to provide a baseline for future studies. A systematic literature search was performed in PubMed, Web of Science and EMBASE databases. Search terms included chronic obstructive lung diseases and ACTs. Studies were independently selected by the investigators according to the eligibility criteria. After screening, 49 articles remained for further analysis. Data are summarized according to the type of outcome measure. 48 (98%) studies performed pulmonary function tests, 19 (39%) assessed expectorated sputum, 10 (20%) parameters related to disease exacerbation, 8 (16%) oxygenation, 8 (16%) patient-reported outcomes, 5 (10%) exercise capacity and 5 (10%) applied imaging techniques. The synthesis of results showed a high discrepancy between studies due to differences in study design, population and the application of techniques. Since no 'gold standard' method could be identified, a combination of different outcome measures is recommended to gain a better understanding and to identify the potential effects of ACTs. An overview of important considerations has been provided to assist researchers in their choice of outcomes in future studies.


Mycotic common iliac artery aneurysm complicating methicillin-resistant Staphylococcus aureus bacteremia: an unusual cause of ureteric obstruction.
A 60-year-old man presented with ureteric obstruction secondary to a mycotic right common iliac artery aneurysm complicating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The diagnosis of MRSA was not known at the time of surgery, and in situ replacement of the aneurysm using a rifampicin-bonded prosthesis was performed. The patient made a full recovery, and to date there is no evidence of residual or recurrent infection. To our knowledge, this is the first reported case of mycotic iliac aneurysm infected with MRSA in the literature. We discuss the consequences and the considerable diagnostic and therapeutic problems that arise.


The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of type 1 and type 2 diabetes in relation to pregnancy.
Strict control of blood glucose levels should be pursued before conception and maintained throughout the pregnancy (glycohaemoglobin [HbA(1c)] level as close as possible to the reference range). Before conception: high-dose (5 mg daily) folate supplementation should be commenced; oral hypoglycaemic agents should be ceased; and diabetes complications screening should take place. Management should be by a multidisciplinary team experienced in the management of diabetes in pregnancy. Blood glucose monitoring is mandatory during pregnancy, and targets are: fasting 4.0-5.5 mmol/L; postprandial < 8.0 mmol/L at 1 hour; < 7 mmol/L at 2 hours. A first trimester nuchal translucency (possibly with first trimester biochemical screening with pregnancy-associated plasma protein A and beta-human chorionic gonadotropin) should be offered. Ultrasound should be performed for fetal morphology at 18-20 weeks, if required, for cardiac views at 24 weeks and for fetal growth at 28-30 and 34-36 weeks. Induction of labour or operative delivery should be based on obstetric and/or fetal indications. Level 3 neonatal nursing facilities may be required and should be anticipated when birth occurs before 36 weeks, or if there has been poor glycaemic control. Insulin requirements fall rapidly during labour and in the puerperium. At this time, close monitoring and adjustment of insulin therapy is necessary.


Correction to: Simulated microgravity significantly altered metabolism in epidermal stem cells.
The affiliation given for Yan Cui in this article is not correct. The following is the correction affiliation.


Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms.
Expression of macrophage inhibitory cytokine-1 (MIC-1), a divergent transforming growth factor-beta family member, and its murine ortholog, growth/differentiation factor-15 (GDF-15), is induced in hepatocytes by surgical and chemical injury and heat shock. Here, we demonstrate that the regulation of GDF-15/MIC-1 expression may be evolutionarily conserved because MIC-1 was induced in diseased human livers. Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation. Although tumor necrosis factor (TNF) induced GDF-15 expression, injury-elicited Gdf15 expression was not reduced in mice deficient for both TNF receptor subtypes. Furthermore, although the stress sensor p53 is known to induce GDF-15/MIC-1 expression, injury-elicited Gdf15 expression was unchanged in p53 null mice. Our results demonstrate that GDF-15 induction is an immediate early response to liver injury that can occur through TNF and p53 independent pathways.


Changes in the reproductive biology of Biomphalara glabrata infected with different doses of Echinostoma paraensei miracidia.
The egg-laying rate, number of egg masses, number of eggs/mass, number of eggs hatched/snail and egg viability of Biomphalaria glabrata exposed to different doses (5 and 50) of Echinostoma paraensei miracidia were analyzed as indicators of reproductive activity. Polystyrene plates were placed in aquariums containing the snails and every other day for four weeks after infection the plates were removed to count the number of egg masses and eggs laid. After this, the plates were numbered individually and placed in new aquariums free of snails and the egg masses were observed daily to determine the hatching rate. On average there was an increase in the parameters evaluated in the infected snails in relation to the controls (uninfected snails), except for egg viability, which was significantly lower in the groups infected with 50 miracidia. These findings indicate that when infected, this host snail is able to increase its reproductive activity, suggesting an ecological strategy to maintain the species.


Antibacterial and cytotoxic activities of new sphingolipids and other constituents isolated from Cissus incisa leaves.
Cissus incisa is used in traditional Mexican medicine to treat certain ailments, infectious or cancerous diseases. Excepting for our previous research, this species had no scientific reports validating its traditional use. In this study, we evaluated the antibacterial and cytotoxic properties of the sphingolipids and others phytocompounds isolated from C. incisa leaves to increase the scientific knowledge of the Mexican flora. The antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria by the Microdilution method. Meanwhile, the cytotoxic potential was determined on six human cancer cells: PC3, Hep3B, HepG2, MCF7, A549, and HeLa; using an aqueous solution cell proliferation assay kit. A cell line of immortalized human hepatocytes (IHH) was included as a control of non-cancerous cells. Selectivity index (SI) was determined only against the hepatocellular carcinoma cell lines. The phytochemical investigation of C. incisa leaves resulted in the isolation and characterization of five compounds: 2-(2'-hydroxydecanoyl amino)-1,3,4-hexadecanotriol-8-ene (1), 2,3-dihydroxypropyl tetracosanoate (2), β-sitosterol-D-glucopyranoside (3), α-amyrin-3-O-β-D-glucopyranoside (4), and a mixture of cerebrosides (5). Until now, this is the first report of the sphingolipids (1), (5-IV) and (5-V). Only the compound (4) and cerebrosides (5) exhibited antibacterial activity reaching a MIC value of 100 μg/mL against Pseudomonas aeruginosa resistant to carbapenems. While, the acetylated derivate of (3), compound (3Ac) showed the best cytotoxic result against PC3 (IC50 = 43 ± 4 μg/mL) and Hep3B (IC50 = 49.0 ± 4 μg/mL) cancer cell lines. Likewise, (3Ac) achieved better SI values on HepG2 and Hep3B cell lines. This research reveals the importance of study medicinal plants, to identify bioactive molecules as sources of potential drugs. The presence of these compounds allows us to justify the use of this plant in traditional Mexican medicine.


Purification and characterization of mouse hypoxanthine-guanine phosphoribosyltransferase.
Hypoxanthine-guanine phosphoribosyltransferase (HGPR transferase) (EC 22.214.171.124) has been purified approximately 4500-fold to apparent homogeneity from mouse liver. The procedure involves the use of affinity chromatography and was designed to be readily adaptable to small scale isolations. The enzyme appears to be composed of 3 subunits of identical molecular weight (27,000 per subunit). The subunit molecular weight has also been determined by the analysis of radioactively labeled HGPR transferase immunoprecipitated from wild type and mutant (HGPR transferase) mouse tissue culture cell lines.


Association between organizational climate and perceptions and use of an innovation in Swedish primary health care: a prospective study of an implementation.
There is a need for new knowledge regarding determinants of a successful implementation of new methods in health care. The role of a receptive context for change to support effective diffusion has been underlined, and could be studied by assessing the organizational climate. The aim of this study was to assess the association between organizational climate when a computer-based lifestyle intervention tool (CLT) was introduced in primary health care (PHC) and the implementation outcome in terms of how the tool was perceived and used after 2 years. The CLT was offered to 32 PHC units in Sweden, of which 22 units agreed to participate in the study. Before the introduction of the CLT, the creative climate at each participating unit was assessed. After 24 months, a follow-up questionnaire was distributed to the staff to assess how the CLT was perceived and how it was used. A question on the perceived need for the CLT was also included. The units were divided into three groups according to the creative climate: high, medium and low. The main finding was that the units identified as having a positive creative climate demonstrated more frequent use and more positive perceptions regarding the new tool than those with the least positive creative climate. More positive perceptions were seen at both individual and unit levels. According to the results from this study there is an association between organizational climate at baseline and implementation outcome after 2 years when a tool for lifestyle intervention is introduced in PHC in Sweden. Further studies are needed before measurement of organizational climate at baseline can be recommended in order to predict implementation outcome.


Clinicopathologic and molecular characterization of myeloid neoplasms with isolated t(6;9)(p23;q34).
The t(6;9)(p23;q34);DEK-NUP214 [t(6;9)] abnormality is found in 0.7-1.8% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). FLT3-ITD mutations are detected in t(6;9) patients. The t(6;9) abnormality is associated with poor outcomes. We studied the clinicopathologic and molecular profiles of patients with AML/MDS carrying t(6;9). We collected clinical data of nine patients with AML/MDS with isolated t(6;9) (median age = 41 years; male/female = 4/5) and genotyped DNAs using whole exome, Sanger, and targeted sequencing. Our cohort was characterized by frequent multilineage dysplasia (56%), absence of phospho-STAT3/STAT5 expression, presence of myeloid markers (CD13, CD33, CD34, CD117, HLA-DR) with an aberrant expression of CD7, and poor outcome (median survival of 20 months). Although basophilia has been described in association with t(6;9), we observed lack of marrow basophilia in our cohort. Molecularly, 83% (5/6) of patients with AML/MDS with t(6;9) were characterized by at least one somatic mutation. Among them, four patients showed multiple mutations. FLT3-ITD mutations were detected in 33% of patients (2/6); 80% (4/5) of mutant patients died even after hematopoietic stem cell transplantation. Our data demonstrated that AML/MDS patients with t(6;9) have diverse molecular mutations regardless of the presence of FLT3 mutations, which may contribute to their poor survival outcomes.


Multicolor FISH (UroVysion) facilitates follow-up of patients with high-grade urothelial carcinoma of the bladder.
The aim of the present prospective study was to assess the diagnostic benefit of UroVysion (Vysis-Abbott Laboratories, Downers Grove, IL) in the follow-up of patients with a history of high-grade non-muscle-invasive urothelial carcinoma of the bladder (NMIBC). An unselected cohort of 25 patients with a history of high-grade NMIBC was prospectively followed up by office-based cystoscopy, cytology, and UroVysion in 210 events. The sensitivity and specificity for standard combined cystoscopy and cytology were 78% and 83%, respectively. UroVysion yielded a considerably higher detection rate with 94% and 93%, respectively. In 89% of the follow-up events of patients with a history of previous carcinoma in situ (CIS) and negative cystoscopy but a positive UroVysion finding, CIS recurrence was noticed within 5 months. UroVysion is a worthwhile approach in patients with previous CIS, a high risk for the development of CIS, or previous unequivocal cytology suggestive of CIS, especially during or shortly after instillation therapy.


Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies.
The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. The prevalence of proper registration and reporting is still very low in depression trials.


Pleiotropic effects of environment-sensitive genes affecting fitness in relation to postmating reproductive isolation.
With regard to speciation in sexually reproducing organisms, some population geneticists continue to argue about the relative merits of sympatry versus allopatry. However, all workers seem quite comfortable with the conventional scenario depicting how reproductive isolation arises between subpopulations in the state of incipient speciation. This view according to which the evolution of reproductive isolation mainly results from some genetic divergence consecutive to a substantial restriction in gene flow is questioned here. A verbal model is described in which gene flow is no longer seen as being first interrupted by a mere physical barrier. The model is based on limited genetic changes at loci influencing fitness but it places two important constraints on the properties of the genetic elements involved in it. One of them is concerned with the environment-sensitivity of the mutations implicated in the process, and the other with their presumed pleiotropic action on a behavioural trait.


Atraumatic avascular necrosis of the head of the talus: a case report.
Avascular necrosis of the talus has frequently been reported following trauma. The incidence of avascular necrosis has been reported to be as high as 50% for Hawkins Type II talar fractures and to range from 75-100% for Type III fracture-dislocations. The resultant avascular necrosis has been reported to occur primarily in the body and dome of the talus with apparent sparing of the head of the talus. The close association of trauma to avascular necrosis of the talus has been alluded to by Cobey and others. Reports of avascular necrosis of the talus, without an antecedent history of trauma, have been rare. This paper presents a case of atraumatic avascular necrosis of the talar head.


The effect of paraffin and exercise on hand function in persons with scleroderma: a series of single case studies.
The purpose of this study was to investigate whether the use of paraffin and active hand exercises would improve activity and participation in persons with scleroderma. In this series of three single case studies, participants used paraffin and performed active hand exercises daily for eight weeks. To assess hand function, measures of body function/structure and activity/participation were taken at baseline, at one month and at two months after intervention. All participants experienced clinically significant improvements in both body function/structure measurements of hand function and in their ability to participate in activities. Significant improvements were found more frequently on body function/structure measures than activity/participation measures. This preliminary study lends support in favor of using paraffin and hand exercises as a treatment to improve hand function related to participation in daily activities in persons with scleroderma. Further research with a larger sample and increased variable control is needed.


The effect of respiratory mode on human middle ear pressure.
The purpose of this study was to examine the effect of respiratory mode on the human middle ear pressure. The partial pressure of carbon dioxide in the venous blood (PvCO2) and the middle ear pressure were increased by hypoventilation, and decreased by hyperventilation. The partial pressure of oxygen in the venous blood showed little change. It was considered that CO2 diffused into the middle ear cleft according to the partial pressure gradient when the PvCO2 was elevated by hypoventilation, resulting in increase of the middle ear pressure, whereas CO2 diffused into the blood from the middle ear cleft when the PvCO2 was reduced by hyperventilation, resulting in decrease of the middle ear pressure. These findings suggest that bidirectional gas exchange via the middle ear mucosa functions actively in the human middle ear and plays an essential role in the regulation of the middle ear pressure.


PRMT1 inhibition induces differentiation of colon cancer cells.
Differentiation therapy has been recently revisited as a prospective approach in cancer therapy by targeting the aberrant growth, and repairing the differentiation and cell death programs of cancer cells. However, differentiation therapy of solid tumors is a challenging issue and progress in this field is limited. We performed High Throughput Screening (HTS) using a novel dual multiplex assay to discover compounds, which induce differentiation of human colon cancer cells. Here we show that the protein arginine methyl transferase (PRMT) type 1 inhibitor, MS023, is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Differentiation changes in the highly aggressive human colon cancer cell line (HT-29) were proved by proteomic and genomic approaches. Growth of HT-29 xenograft in nude mice was significantly delayed upon MS023 treatment and immunohistochemistry of tumor indicated differentiation changes. These findings may lead to development of clinically effective anti-cancer drugs based on the mechanism of cancer cell differentiation.


Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study).
In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS.


Analysis of acid-base disorders in an ICU cohort using a computer script.
Acid-base status is important for understanding pathophysiology, making a diagnosis, planning effective treatment and monitoring progress of critically ill patients. Manual calculations are cumbersome, easily result in wrong conclusions. We wanted to develop an automated assessment of acid-base status. A simplified adaptive MATLAB script processing all available theory to date was created, evaluated and used on blood gas analyses drawn immediately after admission to ICU. The script was compared to golden standard, calculating manually by two experienced ICU physicians. Results from the script correlated completely with detailed manual calculations of randomly chosen 100 blood gas results and it was able to deliver complex data on cohort level with advanced graphics. The initial blood gas analyses from 8875 admissions constituted the cohort, of which 4111 (46.3%) were normal. Respiratory acidosis was the primary disturbance in 2753 (31.0%) and metabolic acidosis in 464 (5.2%). Respiratory alkalosis was the primary disturbance in 1501 (17.0%) and metabolic alkalosis in 46 (0.5%). Of the disturbances 74.7% were mixed with two and 2.1% with three simultaneous disturbances. Acidoses were less compensated compared to alkaloses. Acid-base theories are developed on ideal models and not on critical care patients, they require inputs that might not be available, and therefore, estimations are needed. In our cohort, it was difficult to develop a working script based on Stewart, whereas Boston/Copenhagen worked better. Acidoses were more common and more deviated compared to alkaloses.


Suppressive performance of food waste composting with polylactic acid: Emphasis on microbial core metabolism pathways and mechanism.
The aim of this study was to assess the effect of polylactic acid (PLA) on microbial community composition and core metabolism pathways in food waste (FW) composting. The presence of PLA negatively influenced microbial community richness and decreased respectively the abundance of Bacillus, Halocella and Cellvibrio at mesophilic, thermophilic and mature phases. Analysis of microbial metabolism at the gene level help to understand the mechanism in co-composting with FW and PLA. The expression of core functional genes related to lactide metabolism was stimulated by PLA degradation at thermophilic and mature phases. The sum of absolute abundance of functional genes that involved in first and second carbon oxidation of tricarboxylic acid cycle was decreased due to the existence of PLA. The transformation between 2-Oxoglutarate and Succinyl-CoA were interfered in thermophilic phase, which might result in the lower germination index in PLA group (115%) than that in control (186%).


Mir-664 promotes osteosarcoma cells proliferation via downregulating of FOXO4.
Uncontrol cell growth and proliferation is acknowledged to responsible for cancer-related deaths by disorganizing the balance of growth promotion and growth limitation. Aberrant expression of microRNA play essential roles in cancer development, leads to cell proliferation, growth and survival, and promotes the development of various human tumors, including osteosarcoma. Elucidating the molecular mechanism of this abnormality in osteosarcoma carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. The expression of miR-664 in osteosarcoma cell lines and osteosarcoma tissues was examined using real-time PCR. The effects of miR-664 on osteosarcoma cell proliferation were evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, colony formation and Anchorage-independent growth ability assay. The effect of miR-664 on FOXO4 was determine by luciferase assays and western blot assay. The expression of miR-664 was markedly upregulated in osteosarcoma cell lines and tissues, and upregulation of miR-664 enhanced, whereas downregulation of miR-664 inhibited the proliferation of osteosarcoma cells in vivo. Furthermore, using bioinformatics and biological approaches, we showed that miR-664 directly targeted and suppressed the expression of tumor suppressors FOXO4. Our findings suggest that miR-664 functions as an oncogene miRNA and has an important role in promoting human osteosarcoma cell proliferation by suppressing FOXO4 expression. These data suggests that miR-664 may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in osteosarcoma.


Incorporation of the nanoencapsulated polyphenolic extract of Ferula persica into soybean oil: Assessment of oil oxidative stability.
In the present study, for the first time, the biological activities of Ferula persica extract (FPE) coated with locust bean gum (LBG) and chitosan in W/O/W emulsions were investigated. Based on the findings, the Z-average size of emulsions coated by chitosan, LBG, and the complex of chitosan and LBG (1:1) (CCL) was 115.47, 128.37, and 68.12 nm, respectively. The encapsulation efficiency of the phenolic extracts in the powder produced by chitosan, LBG, and CCL decreased from 85.3 to 64.1, from 89 to 71.4, and from 93.3% to 77.9% during 24-day storage, respectively. Also, the application of the coating in the encapsulation of FPE increased the antioxidant efficacy in soybean oil while compared with tert-butylhydroquinone (TBHQ) and un-encapsulated FPE. In this regard, The FPE nanoencapsulated by CCL showed the best antioxidative activity in soybean oil, followed by the FPE of nanoencapsulated by LBG and chitosan, respectively, which can be correlated with higher levels of polyphenolic compounds release over time in the sample coated with CCL. In this context, the encapsulation with CCL can be proposed as a promising technique to improve the antioxidant activity of extracts.


F.J.J. Buytendijk's concept of an anthropological physiology.
In his concept of an anthropological physiology, F.J.J. Buytendijk has tried to lay down the theoretical and scientific foundations for an anthropologically-oriented medicine. The aim of anthropological physiology is to demonstrate, empirically, what being specifically human is in the most elementary physiological functions. This article contains a sketch of Buytendijk's life and work, an overview of his philosophical-anthropological presuppositions, an outline of his idea of an anthropological physiology and medicine, and a discussion of some epistemological and methodological problems. It is demonstrated that Buytendijk's design of an anthropological physiology is fragmentary and programmatic and that his methodology offers few points of contact for specific anthropological experimental research. Notwithstanding, it is argued that Buytendijk's description of the subjective, animated body forms a pre-eminent point of reference for all research in physiology and psychology in which the specific human aspect is not ignored beforehand.


A comparison of product yields and inorganic content in process streams following thermal hydrolysis and hydrothermal processing of microalgae, manure and digestate.
Thermal hydrolysis and hydrothermal processing show promise for converting biomass into higher energy density fuels. Both approaches facilitate the extraction of inorganics into the aqueous product. This study compares the behaviour of microalgae, digestate, swine and chicken manure by thermal hydrolysis and hydrothermal processing at increasing process severity. Thermal hydrolysis was performed at 170°C, hydrothermal carbonisation (HTC) was performed at 250°C, hydrothermal liquefaction (HTL) was performed at 350°C and supercritical water gasification (SCWG) was performed at 500°C. The level of nitrogen, phosphorus and potassium in the product streams was measured for each feedstock. Nitrogen is present in the aqueous phase as organic-N and NH3-N. The proportion of organic-N is higher at lower temperatures. Extraction of phosphorus is linked to the presence of inorganics such as Ca, Mg and Fe in the feedstock. Microalgae and chicken manure release phosphorus more easily than other feedstocks.


Investigating NF-κB signaling in lung fibroblasts in 2D and 3D culture systems.
Inflammatory respiratory diseases are amongst major global health challenges. Lung fibroblasts have been shown to play a key role in lung inflammatory responses. However, their exact role in initiation and maintenance of lung diseases has remained elusive partly due to the limited availability of physiologically relevant in vitro models. Therefore, developing new tools that enable investigating the molecular pathways (e.g. nuclear factor-kappa B (NF-κB) activation) that underpin inflammatory responses in fibroblasts could be a valuable resource for scientists working in this area of research. In order to investigate NF-κB activation in response to pro-inflammatory stimuli in real-time, we first developed two detection systems based on nuclear localization of NF-κB by immunostaining and luciferase reporter assay system. Furthermore using electrospun porous scaffolds, with similar geometry to human lung extracellular matrix, we developed 3D cultures of lung fibroblasts allowing comparing NF-κB activation in response to pro-inflammatory stimuli (i.e. TNF-α) in 2D and 3D. Our data clearly show that the magnitude of NF-κB activation in 2D cultures is substantially higher than 3D cultures. However, unlike 2D cultures, cells in the 3D model remained responsive to TNF-α at higher concentrations. The more subdued and wider dynamic range of NF-κB responses in 3D culture system was associated with a different expression pattern for TNF receptor I in 3D versus 2D cultures collectively reflecting a more in vivo like TNF receptor I expression and NF-κB activation pattern in the 3D system. Our data suggest that lung fibroblasts are actively involved in the pathogenesis of lung inflammation by activation of NF-κB signaling pathway. The 3D culture detection system provides a sensitive and biologically relevant tool for investigating different pro-inflammatory events involving lung fibroblasts.


Human buccal assay for evaluation of the mucosal irritation potential of drugs.
We applied drugs in aqueous gels to the buccal mucosae of normal volunteers to develop an assay of gastrointestinal irritation potential. We studied effects of pH, concentrations, and formulations. We evaluated irritation by subjects' reports of their sensations and observers' grading of visible reactions. On an irritation log ranking scaled 0 to 5, placebo gels produced virtually no irritation, except those formulated at pH 1, 2, and 14. Albuterol, furosemide, and methyldopa produced essentially no irritation. Minutes of exposure to sodium indomethacin, sodium naproxen, and propranolol (at, respectively, pH 8.2, 9.6, and 4.8 and concentrations of 12%, 40%, and 8%) caused ulceration that took up to weeks to heal. Acid forms of naproxen and indomethacin caused minimal or no irritation. Although irritation models based on one gastrointestinal area have limitations, our results indicate that the minimally invasive buccal assay allows ranking of contact irritation potential of drugs and formulations that could aid in selecting optimum formulations for clinical use.


Current Nutrition Practice in Cardiac Rehabilitation Programs.
This study sought to determine current practice regarding nutrition care within cardiac rehabilitation (CR) programs, including perceived barriers and facilitators to providing nutrition care in this setting. A cross-sectional survey was conducted in October and November 2019. Potential participants were program coordinators, identified through the Australian Cardiovascular Health and Rehabilitation Association program directory and invited to participate via e-mail. Forty-nine respondents (response rate: 13%) are included in this analysis. Programs provided group (n = 42, 86%) and/or individual (n = 25, 51%) nutrition education, and most were supported by a dietitian (63%). However, the availability of dietitians and nutrition care provided at CR was variable. For example, individual education was consistently provided at 13 programs and usually by health professionals other than dietitians. Eight programs (16%) used a formal behavior change framework for nutrition care. Generally, respondents were positive about the role of nutrition; CR coordinators perceived nutrition as a valuable component of the program, and that they had good nutrition knowledge. An identified barrier was the financial resources available to support the provision of nutrition care. To ensure that patients receive the benefits of evidence-based nutrition care, program staff may require additional support, particularly regarding the use of evidence-based behavior change techniques. Key facilitators that may be leveraged to achieve this include the high value and priority that CR program coordinators place on nutrition care.


Influence of in vivo interferon treatment on mitogen responsiveness of T-and B-cells is dependent on the mouse genotype.
Intravenous inoculation of moderate doses of viral interferon (up to 10(4) I.U./mouse) induced subsequent modification of the mitogen responsiveness of T-and B-lymphocytes from the spleen. The modulation, however, was dependent on the mouse genotype. Whereas BALB/c mice demonstrated enhanced T-cell responses (especially to PHA), C57B1/6 mice were generally suppressed in their T-cell response by the same treatment. B-cell proliferation to LPS showed a moderate enhancement in both strains, probably due to activation of accessory cells.


Comparison of different methods for lung immobilization in an animal model.
Respiratory-induced motion introduces uncertainties in the delivery of dose in radiotherapy treatments. Various methods are used clinically, e.g. breath-holding, while there is limited experience with other methods such as apneic oxygenation and high frequency jet ventilation (HFJV). This study aims to compare the latter approaches for lung immobilization and their clinical impact on gas exchange in an animal model. Two radiopaque tumor surrogate markers (TSM) were placed in the central (cTSM) and peripheral (dTSM) regions of the lungs in 9 anesthetized and muscle relaxed pigs undergoing 3 ventilatory interventions (1) HFJV at rates of 200 (JV200), 300 (JV300) and 400 (JV400) min-1; (2) apnea at continuous positive airway pressure (CPAP) levels of 0, 8 and 16 cmH2O; (3) conventional mechanical ventilation (CMV) as reference mode. cTSM and dTSM were visualized using fluoroscopy and their coordinates were computed. The ventilatory pattern was registered, and oxygen and carbon dioxide (pCO2) partial pressures were measured. The highest range of TSM motion, and ventilation was found during CMV, the lowest during apnea. During HFJV the amount of motion varied inversely with increasing frequency. The reduction of TSM motion at JV300, JV400 and all CPAP levels came at the cost of increased pCO2, however the relatively low frequency of 200 min-1 for HFJV was the only ventilatory setting that enabled adequate CO2 removal. In this model, HFJV at 200 min-1 was the best compromise between immobilization and gas exchange for sessions of 10-min duration.


Protective effect of coadministered superoxide dismutase and catalase against stress-induced gastric mucosal lesions.
1. There are conflicting reports as to the protective effect of coadministered native superoxide dismutase (SOD) and catalase against gastric mucosal lesions in rats with water immersion restraint (WIR) stress. It is unclear how coadministered native SOD and catalase protect against WIR stress-induced gastric mucosal lesions. Therefore, in the present study, we re-examined the protective effect of coadministered native SOD and catalase against gastric mucosal lesions in rats with WIR stress. 2. Gastric mucosal lesions were induced in Wistar rats by 3 h WIR. Rats were injected subcutaneously with a mixture of purified bovine erythrocyte SOD and bovine liver catalase 1 h before the onset of WIR. Ulcer index, serum SOD, catalase and xanthine oxidase (XO), uric acid and gastric mucosal SOD, catalase, XO, myeloperoxidase (MPO; an index of tissue neutrophil infiltration), non-protein sulfhydryl (NP-SH) and thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) were assayed in all rats used. 3. Rats with 3 h WIR showed gastric mucosal lesions. Pre-administration of SOD plus catalase to rats with WIR prevented lesion formation. In the serum of rats with WIR alone, XO activity and uric acid concentration increased, whereas SOD and catalase activities did not change. Pre-administration of SOD plus catalase to rats with WIR did not affect increased serum XO activity and uric acid concentration, but did increase serum SOD and catalase activities. In the gastric mucosa of rats with WIR alone, increases in MPO activity and TBARS concentration and a decrease in NP-SH concentration occurred, whereas XO, SOD and catalase activities did not change. Pre-administration of SOD plus catalase to rats with WIR attenuated the changes in gastric mucosal MPO activity and TBARS and NP-SH concentrations, but did not affect gastric mucosal XO, SOD and catalase activities. Pre-administration of SOD plus catalase (in an inactivated form) to rats with WIR had no effect on gastric mucosal lesion formation and the levels of serum and gastric mucosal parameters studied. 4. These results indicate that coadministered native SOD and catalase protect against gastric mucosal lesions in rats with WIR stress and suggest that this protective effect of coadministered native SOD and catalase could be due to their activity to scavenge XO-derived active oxygen species that are increased in the blood.


Intrinsically semi-disordered state and its role in induced folding and protein aggregation.
Intrinsically disordered proteins (IDPs) refer to those proteins without fixed three-dimensional structures under physiological conditions. Although experiments suggest that the conformations of IDPs can vary from random coils, semi-compact globules, to compact globules with different contents of secondary structures, computational efforts to separate IDPs into different states are not yet successful. Recently, we developed a neural-network-based disorder prediction technique SPINE-D that was ranked as one of the top performing techniques for disorder prediction in the biannual meeting of critical assessment of structure prediction techniques (CASP 9, 2010). Here, we further analyze the results from SPINE-D prediction by defining a semi-disordered state that has about 50% predicted probability to be disordered or ordered. This semi-disordered state is partially collapsed with intermediate levels of predicted solvent accessibility and secondary structure content. The relative difference in compositions between semi-disordered and fully disordered regions is highly correlated with amyloid aggregation propensity (a correlation coefficient of 0.86 if excluding four charged residues and proline, 0.73 if not). In addition, we observed that some semi-disordered regions participate in induced folding, and others play key roles in protein aggregation. More specifically, a semi-disordered region is amyloidogenic in fully unstructured proteins (such as alpha-synuclein and Sup35) but prone to local unfolding that exposes the hydrophobic core to aggregation in structured globular proteins (such as SOD1 and lysozyme). A transition from full disorder to semi-disorder at about 30-40 Qs is observed in the poly-Q (poly-glutamine) tract of huntingtin. The accuracy of using semi-disorder to predict binding-induced folding and aggregation is compared with several methods trained for the purpose. These results indicate the usefulness of three-state classification (order, semi-disorder, and full-disorder) in distinguishing nonfolding from induced-folding and aggregation-resistant from aggregation-prone IDPs and in locating weakly stable, locally unfolding, and potentially aggregation regions in structured proteins. A comparison with five representative disorder-prediction methods showed that SPINE-D is the only method with a clear separation of semi-disorder from ordered and fully disordered states.


A computer-assisted system for diagnostic workstations: automated bone labeling for CT images.
Although accurate information on thoracolumbar bone structure is essential when computed tomography (CT) images are examined, there is no automated method of labeling all the vertebrae and ribs on a CT scan. We are developing a computer-aided diagnosis system that labels ribs and thoracolumbar vertebrae automatically and have evaluated its accuracy. A candidate bone was extracted from the CT image volume data by pixel thresholding and connectivity analysis. All non-bony anatomical structures were removed using a linear discriminate of distribution of CT values and anatomical characteristics. The vertebrae were separated from the ribs on the basis of their distances from the centers of the vertebral bodies. Finally, the thoracic cage and lumbar vertebrae were extracted, and each vertebra was labeled with its own anatomical number by histogram analysis along the craniocaudal midline. The ribs were labeled in a similar manner, based on location data. Twenty-three cases were used for accuracy comparison between our method and the radiologist's. The automated labeling of the thoracolumbar vertebrae was concordant with the judgments of the radiologist in all cases, and all but the first and second ribs were labeled correctly. These two ribs were frequently misidentified, presumably because of pericostal anatomical clutter or high densities of contrast material in the injected veins. We are confident that this system can contribute usefully as part of a picture archiving and communication system workstation, though further technical improvement is required for identification of the upper ribs.


OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter.
Three positive (PR1-3) and one negative (NR1) transcriptional control domain have been tentatively mapped in the promoter of the human F0F1-ATP synthase beta subunit gene (ATPsyn beta) in the context of expression in myogenic cells. Lipofection of promoter-chloramphenicol acetyltransferase fusion constructs into C2C12 myogenic cells revealed that two of the three positive domains (PR1 and PR2) function in both myoblasts and myotubes, whereas the third positive domain (PR3) and the sole negative domain (NR1) seem to function only in myotubes. PR1 contains a cluster of four CCAAT cis-elements, PR2 is a small 44-base pair region containing an SP1-like motif, and PR3 is a region previously shown to be recognized by both OXBOX- and REBOX-binding factors. By site-directed polymerase chain reaction linker mutations, the activity of the OXBOX/REBOX cis-element in myoblasts is shown to be masked by flanking sequences in PR3. The negative domain, NR1, is located between 300 and 1,000 base pairs upstream from the OXBOX/REBOX elements in a region containing multiple Alu repeats. Mobility gel shift analysis of DNA-protein complexes using competitor DNAs verified the involvement of both OXBOX- and REBOX-binding factors in PR3. Similar experiments show SP1-specific binding at PR2. These data with observations of OXBOX and REBOX-specific binding of an OXBOX/REBOX-like region within the conserved sequence block C of the human mitochondrial DNA D-loop sequence are consistent with the idea that OXBOX- and REBOX DNA-binding factors coordinate the expression of mitochondrial energy genes in highly oxidative tissues by working with well characterized general transcription factors such as SP1 and CCAAT DNA-binding proteins, which exist in the nucleus, and MTF, which exists in the mitochondrion.


Detection of meat-borne trimethylamine based on nanoporous colorimetric sensor arrays.
Trimethylamine (TMA) is a key measurement indicator for meat spoilage. In order to develop simple, cheap, and sensitive sensors for TMA detection, a nanoporous colorimetric sensor array (NCSA) was developed. A sol-gel method has been used to obtain TiO2 nanoporous film as substrate material to improve the sensitivity and stability of the CSA. The sensor enabled the visual detection of TMA gas from the permissible exposure limits (PEL) 10 ppm to 60 ppb concentrations with significant response. Principal component analysis (PCA) was used to characterize the functional relationship between the color difference data and TMA concentrations. Furthermore, the NCSA was used to predict the presence of TMA in Yao-meat. A partial least square (PLS) prediction model was obtained with the correlation coefficients of 0.896 and 0.837 in calibration and prediction sets, respectively. This research suggested that the NCSA offers a useful technology for quality evaluation of TMA in meat.


Do students from rural backgrounds engage in rural family practice more than their urban-raised peers?
In a previous prospective study, students from rural backgrounds were found to be significantly more likely to consider rural practice than their urban-raised peers. The purpose of this study was to determine whether the students with rural backgrounds who participated in the original investigation were more likely than their urban-raised peers to be currently engaged in rural family practice. In Canada, family doctors have the greatest opportunity to practise in rural communities. Consequently, rural and urban background students from the original study who entered the discipline of family medicine as a career were identified for practice location follow-up. Participants were categorised as either rural (population less than 10 000) or urban practitioners according to the population of the community in which they practised. The proportion of rural and urban background students engaged in rural or urban practice was analysed using chi-square and relative risk probability. A total of 78 students from the original cohort were found to be practising family medicine; 22 of them had been rurally raised. Seven (32%) of the rural background students were practising in a rural community, compared to 7 (13%) of the 56 urban background students (RR = 2.55; P < 0.05). Rural background students who went on to complete family medicine residency training were approximately 2.5 times more likely to be engaged in rural practice than their urban-raised peers. Altering medical school admission policy to recruit more rural background applicants should be part of a multi-dimensional approach to increasing the number of rural practitioners.


Addition of ethanol to supercritical carbon dioxide enhances the inactivation of bacterial spores in the biofilm of Bacillus cereus.
Supercritical carbon dioxide (SC-CO2) was used to inactivate Bacillus cereus spores inside biofilms, which were grown on stainless steel. SC-CO2 treatment was tested using various conditions, such as pressure treatment (10-30 MPa), temperature (35-60°C), and time (10-120 min). B. cereus vegetative cells in the biofilm were completely inactivated by treatment with SC-CO2 at 10 MPa and at 35°C for 5 min. However, SC-CO2 alone did not inactivate spores in biofilm even after the treatment time was extended to 120 min. When ethanol was used as a cosolvent with SC-CO2 in the SC-CO2 treatment using only 2-10 ml of ethanol in 100ml of SC-CO2 vessel for 60-90 min of treatment time at 10 MPa and 60°C, B. cereus spores in the biofilm were found to be completely inactivated in the colony-forming test. We also assessed the viability of SC-CO2-treated bacterial spores and vegetative cells in the biofilm by staining with SYTO 9 and propidium iodide. The membrane integrity of the vegetative cells was completely lost, while the integrity of the membrane was still maintained in most spores. However, when SC-CO2 along with ethanol was used, both vegetative cells and spores lost their membrane integrity, indicating that the use of ethanol as a cosolvent with SC-CO2 is efficient in inactivating the bacterial spores in the biofilm.


Recycled, Contaminated, Crumpled Aluminum Foil-Driven Triboelectric Nanogenerator.
With rapid urbanization and global population growth, the amount of wasted aluminum foil is significantly increasing. Most deformed and contaminated foil is difficult to recycle; hence, it is landfilled or incinerated, causing environmental pollution. Therefore, using aluminum foil waste for electricity may be conducive to addressing environmental problems. In this regard, various literatures have explored the concept of energy generation using foil, while a crumple ball design for this purpose has not been studied. Thus, a recycled foil-based crumpled ball triboelectric nanogenerator (RFCB-TENG) is proposed. The crumpled ball design can minimize the effects of contamination on foil, ensuring efficient power output. Moreover, owing to novel crumpled design, the RFCB-TENG has some outstanding characteristics to become a sustainable power source, such as ultralight weight, low noise, and high durability. By introducing the air-breakdown model, the RFCB-TENG achieved an output peak voltage of 648 V, a current of 8.1 mA cm3 , and an optimum power of 162.7 mW cm3 . The structure of the RFCB-TENG is systemically optimized depending on the design parameters to realize the optimum output performance. Finally, the RFCB-TENG operated 500 LEDs and 30-W commercial lamps. This work paves the guideline for effectively fabricating the TENG using waste-materials while exhibiting outstanding characteristics.


The monitoring of nucleotide diphosphate kinase activity by blue native polyacrylamide gel electrophoresis.
Nucleoside diphosphate kinase (NDPK) has been shown to play a pivotal role in modulating a plethora of cellular processes. In this study, we report on a blue native (BN) PAGE technique which allows the facile assessment of NDPK activity and expression. The in-gel detection of NDPK relies on the precipitation of formazan at the site of immobilized enzyme activity. This is achieved by coupling the formation of ATP, as a consequence of gamma-phosphate transfer from NTP to ADP, to hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PDH), oxidized nicotinamide adenine dinucleotide phosphate (NADP), phenazine methosulfate (PMS), and iodonitrotetrazolium chloride (INT). 2-D denaturing gel analysis confirmed that the activity bands corresponded to NDPK as indicated by subunit composition. Furthermore, the sensitivity and specificity of this readily accessible procedure was assessed by monitoring the in-gel activity of NDPK using different concentrations of GTP and CTP as well as deoxynucleoside triphosphates. This electrophoretic technique allows the quick and easy detection of NDPK, a housekeeping enzyme crucial to cell survival.


Comparison of NucliSens and Roche Monitor assays for quantitation of levels of human immunodeficiency virus type 1 RNA in plasma.
We compared the performance of Organon Teknika's NucliSens and Roche Diagnostic Systems' Monitor quantitative human immunodeficiency type 1 RNA assays. Both had similar linearity and sensitivity over most of the dynamic range of the assays, although the Monitor assay was superior at the low range of RNA values while the NucliSens assay was more consistent at higher RNA values. NucliSens generally showed less interassay variability.


Effect of Neck Size on the Inflow Magnitude Evaluated on 4D Flow MRI in Unruptured Internal Carotid Artery Aneurysms.
A neck size >4.0 mm is a risk factor for recanalization after coil embolization. The high inflow magnitude of pretreatment wide-neck aneurysms may be correlated to recanalization. We aimed to elucidate the effect of the neck size on the inflow magnitude evaluated on four-dimensional (4D) flow magnetic resonance imaging (MRI) in pretreatment unruptured internal carotid artery (ICA) aneurysms. Thirty-three untreated ICA aneurysms were subjected to 4D flow MRI to evaluate the inflow magnitude parameters including the maximum spatially-averaged inflow velocity (MSAIV), maximum inflow velocity, maximum inflow rate (MIR), and their ratios to each corresponding flow parameter in the parent artery. The neck size was linearly correlated to all inflow parameters investigated in this study. A strong correlation was observed between the neck size and the following: MSAIV (r = .755, p < .0001), MIR (r = .715, p < .0001), MSAIV ratio (r = .724, p < .0001), and MIR ratio (r = .741, p < .0001). The predicted value of MIR ratio of an aneurysm with the neck size of 4.0 mm was 23.0% and 20.6%, based on the linear regression equation of all aneurysms and on that of aneurysms with the neck size >4.0 mm, respectively. The neck size was linearly correlated with the inflow magnitude of unruptured ICA aneurysms. Inflow magnitude evaluation using 4D flow MRI may help to hemodynamically identify aneurysms with a high risk of recanalization after endovascular coil embolization.


Role of serum digoxin assay in patient management.
Serum digoxin assay is a useful clinical tool in monitoring the administration of digoxin. Its value, however, is generally overrated; judicious use of it applies only to specific clinical problems. Its primary use involves assay values at the two ends of the scale: low ranges may help detect noncompliant patients or those with serious absorption difficulties. Higher ranges are helpful in the clinical recognition of digitalis toxicity.


Surgical correction of astigmatism by microwedge resection of the limbus.
This paper presents a preliminary report on an approach to the surgical correction of corneal astigmatism, ie, the microwedge resection of the cornea, analyzes the quantitative aspects of the surgical treatment, and describes the Jensen double-bladed microsurgical knife designed for making calibrated-uniform microsurgical wedge resections of the cornea. This technique makes correction of even small increments of corneal astigmatism possible.


Synthesis of aminophosphonate haptens for an aminoacylation reaction between methyl glucoside and a beta-alanyl ester.
Two 2-aminophosphonate haptens derived from methyl alpha-D-glucopyranoside were synthesized to mimic the transition-state of a transesterification reaction between methyl alpha-D-glucopyranoside and 4-nitrophenylester of tert-BOC-beta-alanine. Two sets of monoclonal antibodies were generated against these haptens.


miR-148a inhibits colitis and colitis-associated tumorigenesis in mice.
miR-148a has been shown to regulate inflammation, immunity and the growth of certain tumors, but its roles in colitis and colorectal tumorigenesis remain largely undetermined. Here we found miR-148a-deficient mice to be more susceptible to colitis and colitis-associated tumorigenesis. Both were associated with increased nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling. Bone marrow- and non-bone marrow-derived miR-148a contributed to colitis and colitis-associated tumorigenesis. miR-148a loss of heterozygosity exacerbated Apcmin/+ colon and small intestinal spontaneous tumor development. Restoring miR-148a expression prevented both spontaneous and carcinogen-induced colon tumor development. miR-148a was downregulated in human inflammatory bowel disease (IBD) and colorectal cancer patient tissues. This correlated with a high degree of miR-148a promoter methylation mediated by a complex comprised of P65 and DNA methyltransferase 3 alpha (DNMT3A). miR-148a directly targets several well-accepted upstream regulators of NF-κB and STAT3 signaling, including GP130, IKKα, IKKβ, IL1R1 and TNFR2, which leads to decreased NF-κB and STAT3 activation in macrophages and colon tissues. Our findings reveal that miR-148a is an indirect tumor suppressor that modulates colitis and colitis-associated tumorigenesis by suppressing the expression of signaling by NF-κB and STAT3 and their pro-inflammatory consequences.


Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients?
The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.


Semaphorin 3F forms an anti-angiogenic barrier in outer retina.
Semaphorins are known modulators of axonal sprouting and angiogenesis. In the retina, we identified a distinct and almost exclusive expression of Semaphorin 3F in the outer layers. Interestingly, these outer retinal layers are physiologically avascular. Using functional in vitro models, we report potent anti-angiogenic effects of Semaphorin 3F on both retinal and choroidal vessels. In addition, human retinal pigment epithelium isolates from patients with pathologic neovascularization of the outer retina displayed reduced Semaphorin 3F expression in 10 out of 15 patients. Combined, these results elucidate a functional role for Semaphorin 3F in the outer retina where it acts as a vasorepulsive cue to maintain physiologic avascularity.


Fast methods for screening of trichothecenes in fungal cultures using GC-MS/MS.
Fast methods for screening for production of simple and macrocyclic trichothecenes, produced on solid substrates were developed. Crude extracts fromFusarium cultures grown on yeast extract sucrose agar (approx. 0.3 cm(2) culture) were derivatised using pentafluoropropionic anhydride and analysed by GC - tandem mass spectrometry using a Finnigan GCQ(+) ion trap. The MS was operated in the EI(+) multiscan mode allowing simultaneous full scan and MS/MS of 3-4 parent ions. Production of acetyl T-2 toxin (AT-2), T-2 toxin, HT-2 toxin (HT-2), T-2 triol (T-2TR), T-2 tetraol (T-2TE), neosolaniol (NEO), iso-neosolaniol (I-NEO), scripentriol (SCR), 4,15-diacetoxyscirpenol (DAS), 15-acetoxyscripentriol (15MAS), 4-acetoxyscripentriol (4MAS), nivalenol (NIV), fusarenon-X (F-X), deoxynivalenol (DON), 15-acetoxy-DON (15DON) and 3-acetoxy-DON (3DON) was studied for severalFusarium species. In hydrolysed crude extracts ofStachybotrys albipes, Trichoderma harzianum, andMemnoniella echinata trichodermol was detected, in cultures ofS. chartarum both verrucarol and trichodermol were detected as the heptafluorobuturyl esters after derivatisation with a imidazole based reagent.


Resistance to Bt maize in Mythimna unipuncta (Lepidoptera: Noctuidae) is mediated by alteration in Cry1Ab protein activation.
Bt maize cultivars based on the event MON810 (expressing Cry1Ab) have shown high efficacy for controlling corn borers. However, their efficiency for controlling some secondary lepidopteran pests such as Mythimna unipuncta has been questioned, raising concerns about potential outbreaks and its economic consequences. We have selected a resistant strain (MR) of M. unipuncta, which is capable of completing its life cycle on Bt maize and displays a similar performance when feeding on both Bt and non-Bt maize. The proteolytic activation of the protoxin and the binding of active toxin to brush border membrane vesicles were investigated in the resistant and a control strain. A reduction in the activity of proteolytic enzymes, which correlates with impaired capacity of midgut extracts to activate the Cry1Ab protoxin has been observed in the resistant strain. Moreover, resistance in larvae of the MR strain was reverted when treated with Cry1Ab toxin activated with midgut juice from the control strain. All these data indicate that resistance in the MR strain is mediated by alteration of toxin activation rather than to an increase in the proteolytic degradation of the protein. By contrast, binding assays performed with biotin labelled Cry1Ab suggest that binding to midgut receptors does not play a major role in the resistance to Bt maize. Our results emphasize the risk of development of resistance in field populations of M. unipuncta and the need to consider this secondary pest in ongoing resistance management programs to avoid the likely negative agronomic and environmental consequences.


Biosynthesis of phytosphingosine by the rat.
Labeled C18-phytosphingosine was detected in a glyco-lipid-rich fraction from rat intestine 4 and 24 h after injection of D-erythro[4,5-3H]C18-dihydrosphingosine. The criteria for identification were: (a) co-migration on gas-liquid chromatography of the trimethylsilyl ethers of the free and N-acetylated base with authentic standard, (b) co-migration on thin layer chromatography of the dinitrophenyl derivative with authentic standard, (c) labeled pentadecanol detection by gas-liquid radiochromatography after subjecting intact sphingolipids or a mixture of free long chain bases to periodate oxidation followed by sodium borohydride reduction, and (d) obtainment of the same fragmentation pattern as with authentic standard when the trimethylsilyl ethers of the N-acetylated base were subjected to gas-liquid chromatography-mass spectrometry. Smaller amounts of labeled C18-phytosphingosine were also detected in ceramide- and sphingomyelin-rich fractions of intestine and in liver and kidney. Experiments with germ-free rats strongly suggest that the intestinal flora is not the (sole) site for the biosynthesis of C18-phytosphingosine.


CDDO-me induces apoptosis and inhibits Akt, mTOR and NF-kappaB signaling proteins in prostate cancer cells.
Synthetic oleanolic acid triterpenoid 2-cyano-3,12-dioxooleana-, 9(11)-dien-28-oic acid (CDDO) and its methyl ester (CDDO-Me) and imidazole (CDDO-Im) derivatives exhibit potent antitumor activity against diverse types of tumor cell lines. However, the anticancer activity of these triterpenoids against prostate cancer cells has not been reported. The apoptosis-inducing activity of CDDO-Me in human prostate cancer cell lines was investigated using flow cytometry and immunoblotting. Prostate cancer cells are highly sensitive to CDDO-Me at concentrations of 1.25 to 10 microM. The primary mode of tumor cell destruction was apoptosis as demonstrated by increase in annexin V-FITC binding, activation of procaspases, release of cytochrome c from mitochondria, and inhibition of anti-apoptotic proteins. Furthermore, CDDO-Me inhibited the levels of anti-apoptotic Akt, mTOR and NF-kappaB (p65) signaling molecules. These studies provide a rationale for clinical evaluation of CDDO-Me as adjuvant therapy for treatment of advanced and fatal form of prostate cancer.


Scanning electron microscopy of the development of the mesoderm layer in chick embryos.
The distribution of mesoderm, the structure of mesoderm cells and relationship between mesoderm and ectoderm were examined by SEM in embryos at stages 3 to 5. The mesoderm was displayed by removal of the endoderm and by fracturing the embryos through mesoderm containing regions. Within the mesoderm layer four zones could be distinguished by their cell shape and arrangement--the primitive streak, a multilayered compact area around the margins of the area pellucida, multilayered and loosely arranged cells near the primitive streak and a flattened monolayer of cells around the advancing lateral and anterior edges of the mesoderm sheet. Secretion of basement membrane by the ectoderm was seen to precede the arrival of mesoderm cells. This suggests that ectoderm alone can synthesize basement membrane without mesodermal contribution.


Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line.
To observe the chitooligosaccharides (COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line. CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells, MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells. The clonogenic assay was used to detect the cell viability of 0, 1, 2, 4, 6 and 8 Gy (6 dose grades) in RAY group and RAY + COS group after X-ray, and the cell survival curve was used to analyze the sensitization enhancement ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY + COS group after 48 h treatment. COS inhibited the proliferation of three types of cells. The inhibition rate was positively correlated with the concentration of COS, and the susceptibility of MKN45 cells, SGC7901 cells and BGC823 cells to COS decreased in turn. The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY + COS group (P < 0.01). The cell viabilities of RAY + COS group were lower than those of RAY group at all the dose grades under X-ray exposure (P < 0.01), and the sensitization enhancement ratios of COS on BGC823 cells, MKN45 cells and SGC7901 cells were 1.06, 1.28 and 1.15, respectively. In controlled trials, apoptosis rate and percentage in the G2/M phase of three types of cells in RAY + COS group were higher than those in control group and RAY group, and percentage in the S phase and the G0/G1 phase in RAY + COS group were lower than those in the other two groups (P < 0.01). COS can inhibit the proliferation of three types of human gastric cancer cells and enhance the radiosensitivity by inducing apoptosis and G2/M phase arrest.


YiaC and CobB regulate lysine lactylation in Escherichia coli.
Lysine lactylation (Kla) has recently been reported to participate in regulating transcription in human cells. However, the characterization, regulatory mechanism and functional consequence of Kla in prokaryotes remain unclear. Here, we report that YiaC functions as a lysine lactylase and that CobB serves as a lysine delactylase in the regulation of metabolism. We demonstrate that YiaC catalyzes the addition of Kla, while CobB erases this PTM both in vitro and intracellularly. Moreover, we show that YdiF can catalyze the formation of a lactyl-coenzyme A, which donates lactyl group for Kla. Quantitative proteomic analysis further reveals 446 endogenous Kla sites targeted by CobB and 79 candidates targeted by YiaC in Escherichia coli (E. coli). Furthermore, we present that Kla can influence the functions of metabolic enzymes. Interestingly, we demonstrate that CobB can specifically modulate the activity of PykF by regulating K382la, promoting glycolysis and bacterial growth. Our study identifies the regulatory enzymes and functional network of Kla and reveals a Kla-mediated molecular mechanism catalyzed by CobB for glycolysis regulation in E. coli.


New shallow water species of Caribbean Ircinia Nardo, 1833 (Porifera: Irciniidae).
Seven Ircinia morphospecies were collected from three sites in the Caribbean (Bocas del Toro, Panama; the Mesoamerican Barrier Reef, Belize; and the Florida Keys, United States of America). Previous research used an integrative taxonomic framework (genome-wide SNP sampling and microbiome profiling) to delimit species boundaries among these Ircinia. Here, we present morphological descriptions for these species, six of which are new to science (Ircinia lowi sp. nov., Ircinia bocatorensis sp. nov., Ircinia radix sp. nov., Ircinia laeviconulosa sp. nov., Ircinia vansoesti sp. nov., Ircinia ruetzleri sp. nov.) in addition to one species conferre (Ircinia cf. reteplana Topsent, 1923).


Substance p reversal of electroconvulsive shock and cycloheximide-induced retrograde amnesia.
Subcutaneous post-trial administration of the neuropeptide substance P was found to reverse the amnestic effects of both electroconvulsive shock and cycloheximide. Substance P was observed to reverse the amnestic effects of cycloheximide in both C57B1/6J and heterogeneous strain (HS) mice. Substance P was found to reverse the amnestic effects of electroconvulsive seizures in C57B1/6J animals. Peripheral injections of substance P were also found to facilitate the retention of a single-trial passive avoidance habit in animals of both genotypes, provided a weak footshock was used during training.


Health care costs associated with changing clinics and "walk-in" deliveries: evidence supporting a regionalized health information network.
The objective of the study was to describe the prevalence of changing clinics and "walk-in" deliveries and estimate associated health care costs. This was a retrospective review at an urban teaching hospital over a 6 month period. Principal outcome measures were availability of laboratory data at delivery and the number, type, and costs of duplicated tests for patients receiving various amounts of prenatal care (PNC) at our site. The prevalence of changing clinics, walk-in deliveries, and availability of records in our hospital was applied to the Los Angeles County Medicaid population to calculate the estimated cost of repeated prenatal laboratory studies. Of the 1120 patients delivered by our service, 50% received all PNC at our site, 27% transferred PNC to our site, and 23% of patients were walk-ins for delivery only. Medical records were unavailable in 26% of cases, requiring prenatal laboratory studies repeated. Costs varied by amount of PNC on site (range, $107.00-201.00). Changing clinics and walk-in deliveries are associated with significant health care costs because of redundant laboratory services and personnel costs associated with reviewing and exchanging medical records.


Cervical chordoma: report of a case and the technique of transoral removal.
A case of cervical chordoma in a man of 27 years is described. The clinical features were of progressive spinal cord compression. Treatment was by transoral decompression of the second cervical vertebra and postoperative radiotherapy. The result was favourable and remained so at follow-up after 27 months. The relative merits and scope of the various approaches to the upper cervical vertebrae and the role of radiotherapy and chemotherapy are discussed.


A normative study on visual reaction times and two Stroop colour-word tests.
Two-hundred and nine normal subjects underwent a study aimed at providing norms for some attention tests currently used in neuropsychological examination. Norms were calculated taking into account the demographic variables. Our battery included single visuo-manual and go/no-go reaction times, and two versions of the Stroop Colour-Word Test. For the latter test, we employed a traditional version based on card presentation and a new version based on computer-assisted presentation. We evaluated the intercorrelation of the different tests, and studied the statistical regression models in order to adjust the original scores according to age, education and gender. Normative values were calculated following the Equivalent Scores method. The pattern of intercorrelation of our battery and the regression models of the scores are discussed with reference to the literature. The newly developed computer-assisted presentation of the Stroop test offers some advantages over the traditional version, especially with patients affected by spatial disorders.


Shifting concepts of the fetal-maternal interface: a historical perspective.
The first microscopic images of the human placenta, obtained in the 1830s, revealed the presence of an epithelial lining separating fetal capillaries from maternal blood, which was in later years successively interpreted as maternal endothelial, decidual and finally as "trophoblastic". With this new term, introduced by Hubrecht in 1889, its embryonic/fetal origin was recognized as well as its role in nutrient uptake from maternal blood. Thomas Huxley considered the presence of a decidua as an important feature for mammalian classification, but still mixed up maternal and trophoblastic tissue. Mathias Duval recognized invasive activities by trophoblast in rodents, but over-interpreted the arterial invasion observed in rats. In the human, unusual endovascular cells were first described by Carl Friedländer, but their trophoblastic nature was only recognized in the early 20th century. Nitabuch's description of a continuous fibrinoid layer underneath the basal plate led to the erroneous concept of a borderline separating the trophoblast-invaded upper decidua from the deeper non-invaded uterine tissue. This concept - based on the study of one pregnant uterus - has been made obsolete by later studies of trophoblast invasion. Many erroneous interpretations of placental histology in the past were logical in the context of then current knowledge. A better understanding depended on improved technology which allowed tracing of histological continuity of structural features in space and time. Although identification of cell types increasingly relies on molecular markers, classical histological principles should still be applied in conjunction with newer techniques in order to arrive at a broad understanding of placental development. Understanding past errors in interpreting placental histology should guard us against overconfidence in so-called breakthrough discoveries.


An efficient palladium-benzimidazolyl phosphine complex for the Suzuki-Miyaura coupling of aryl mesylates: facile ligand synthesis and metal complex characterization.
A new class of easily accessible hemilabile benzimidazolyl phosphine ligands has been developed. The ligand skeleton is prepared from commercially available and inexpensive o-phenylenediamine and 2-bromobenzoic acid. With catalyst loading down to 0.5 mol% palladium, excellent catalytic activity towards the Suzuki-Miyaura coupling of aryl mesylates is still observed. This represents the lowest catalyst loading achieved so far for this reaction in general. X-Ray crystallography shows that new ligand L2 is coordinated with Pd in a κ(2)-P,N fashion.


Chronic inflammation and the hallmarks of aging.
Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as "inflammaging," which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty. How the crosstalk between chronic inflammation and other hallmarks of aging underlies biological mechanisms of aging and age-related disease is thus of particular interest to the current geroscience research. This review integrates the cellular and molecular mechanisms of age-associated chronic inflammation with the other eleven hallmarks of aging. Extra discussion is dedicated to the hallmark of "altered nutrient sensing," given the scope of Molecular Metabolism. The deregulation of hallmark processes during aging disrupts the delicate balance between pro-inflammatory and anti-inflammatory signaling, leading to a persistent inflammatory state. The resultant chronic inflammation, in turn, further aggravates the dysfunction of each hallmark, thereby driving the progression of aging and age-related diseases. The crosstalk between chronic inflammation and other hallmarks of aging results in a vicious cycle that exacerbates the decline in cellular functions and promotes aging. Understanding this complex interplay will provide new insights into the mechanisms of aging and the development of potential anti-aging interventions. Given their interconnectedness and ability to accentuate the primary elements of aging, drivers of chronic inflammation may be an ideal target with high translational potential to address the pathological conditions associated with aging.


Different oxygenators for cardiopulmonary bypass lead to varying degrees of human complement activation in vitro.
Complement activation was studied in vitro with six different membrane and bubble oxygenators for cardiopulmonary bypass. There was a similar increase in terminal (C5 to C9) activation with all oxygenators (p less than 0.001), ranging from 281% (117% to 444%) to 453% (225% to 680%) after 60 minutes (median and 95% confidence intervals). C3 activation was not observed with a hollow fiber membrane and a soft shell bubble oxygenator. On the other hand, a capillary membrane, a sheet membrane, a nonporous membrane, and a hard shell bubble oxygenator all induced a similar increase in C3 activation (p less than 0.01), ranging from 107% (23% to 346%) to 272% (88% to 395%) after 60 minutes. The differences in C3 activation could not be explained by the blood contact materials or any other single factor known to induce activation, which suggests that overall complement activation during cardiopulmonary bypass is a multifactorial effect. The tubing set per se induced only minor C3 activation but contributed to the overall formation of terminal complement complex. The study further indicates that an arterial line blood filter prevents activated neutrophils from being reinfused to the patient and should be used regardless of type of oxygenator.


Riedel's thyroiditis and fibrous variant of Hashimoto's thyroiditis: a clinicopathological and immunohistochemical study.
The aim of this study was to analyze and compare clinico pathological aspects of Riedel's thyroiditis (RT) and the fibrous variant of Hashimoto's thyroiditis (HTFV), and to show their immunohistochemical features. We reviewed 6 cases of HTFV and 4 cases of RT. Compared to RT, HTFV patients had hypothyroidism, no pressure symptoms, and frequently diagnostic fine-needle aspiration biopsy (FNAB) cytology. At histology, invasion of surrounding tissues and presence of occlusive phlebitis distinguished RT from HTFV. At immunohistochemistry, RT--compared to HTVF--was characterized by: 1) a more abundant fibrous reaction, and granulocytic, monocytic and eosinophil infiltration; 2) few plasma-cells, CD8+ T- and B-lymphocytes. The results of our study add further evidence regarding the separation of RT and HTFV in their peculiar clinical, laboratory, cyto-histological and immunohistochemical aspects.


PERK participates in cardiac valve development via fatty acid oxidation and endocardial-mesenchymal transformation.
Protein kinase R-like endoplasmic reticulum kinase (PERK) is one of the endoplasmic reticulum (ER) stress sensors. PERK loss-of-function mutations are known to cause Wolcott-Rallison syndrome. This disease is characterized by early-onset diabetes mellitus, skeletal dysplasia, and cardiac valve malformation. To understand the role of PERK in valve formation in vivo, we used an endothelial-specific PERK conditional knockout mice as well as in vitro PERK inhibition assays. We used ProteoStat dyes to visualize the accumulation of misfolded proteins in the endocardial cushion and valve mesenchymal cells (VMCs). Then, VMCs were isolated from E12.5 fetal mice, by fluorescence assisted cell sorting. Proteomic analysis of PERK-deleted VMCs identified the suppression of proteins related to fatty acid oxidation (FAO), especially carnitine palmitoyltransferase II (CPT2). CPT2 is a critical regulator of endocardial-mesenchymal transformation (EndoMT); however how TGF-β downstream signaling controls CPT2 expression remains unclear. Here, we showed that PERK inhibition suppressed, not only EndoMT but also CPT2 protein expression in human umbilical vein endothelial cells (HUVECs) under TGF-β1 stimulation. As a result, PERK inhibition suppressed mitochondrial metabolic activity. Taken together, these results demonstrate that PERK signaling is required for cardiac valve formation via FAO and EndoMT.