Ultrasonic assisted headspace single drop micro-extraction and gas chromatography with nitrogen-phosphorus detector for determination of organophosphorus pesticides in soil.
This work describes optimization of headspace single drop micro-extraction for extraction of five organophosphorus pesticides; thionazin, sulfotep, dimethoate, disulfoton and parathion in soil. Ultrasound has also been used successfully to improve and accelerate the extraction of the analytes from the sample. The optimized extraction performance was obtained when the experimental parameters were set as follows; 3.0 μL of octanol as extraction solvent, high ionic strength (20% sodium chloride), 1:1 (w/v) sample dilution with water, extraction temperature at 60 °C for 30 min; applying ultrasound and without any pH adjustment. The optimized method was linear over the calibration range (5-200 and 10-300 for different analytes) with limits of detection of 0.1-2.0 ng g(-1). The enrichment factor for OPPs was 1.4-12.7 and the method was also reproducible with the relative standard deviations (RSD%) of 2.1-6.9%.


Correlation of plasma 25-hydroxyvitamin D levels with severity of primary hyperparathyroidism and likelihood of parathyroid adenoma localization on sestamibi scan.
To determine the relationship between preoperative plasma 25-hydroxyvitamin D (25[OH]D) levels and severity of primary hyperparathyroidism (PHPT) and to explore whether presurgical 25(OH)D levels could predict the likelihood of positive results on technetium Tc 99m sestamibi scintigraphy. Retrospective analysis. Tertiary university referral center. A total of 421 consecutive patients underwent preoperative sestamibi scintigraphy and parathyroid exploration. Patients with cholecalciferol (vitamin D) deficiency, defined as plasma levels lower than 25 ng/mL, were compared with patients having no vitamin D deficiency. We explored the relationship between 25 (OH)D levels and intact parathyroid hormone (iPTH) levels, alkaline phosphatase (ALKP) levels, adenoma weight, binary sestamibi scan results, and postoperative serum calcium levels (at 1 week and 6 months). We hypothesized that severity of hypovitaminosis D would correlate with severity of PHPT and predict the likelihood of a positive finding on sestamibi scan. Concentrations of iPTH and ALKP and parathyroid adenoma weight were significantly higher in patients with lower 25(OH)D levels (P < .01 for all). Patients with hypovitaminosis D had a greater percentage decrease in serum calcium levels 1 week and 6 months postoperatively (P < .05). Median 25(OH)D levels were lower in patients with positive sestamibi scan results (P < .001). Patients with hypovitaminosis D present with more advanced indices of PHPT. Parathyroid sestamibi scanning is more likely to show positive results for this subset of patients who may then benefit from sestamibi scan-directed surgical intervention.


[Calcitonin: properties and methods of production].
Calcitonin structure, biological activity, formation in organism and methods of production including isolation from natural sources, chemical synthesis and genetic engineering methods are reviewed.


Pertussis toxin attenuates intracranial morphine self-administration.
Mu and delta opioid receptor subtypes are thought to mediate the reinforcing actions of opioids. Since these opioid receptors use pertussis toxin (PTX)-sensitive inhibitory G-proteins for signal transduction, we determined whether PTX would block the opioid reinforcement signals produced by intrahippocampal or intraventral tegmental area (VTA) injections of morphine in rats. Hippocampal PTX pretreatment prevented the acquisition of intrahippocampal morphine self-administration. Similarly, in rats previously trained to self-administer morphine in the VTA, PTX injections in the VTA abolished morphine self-administration behavior, while sparing behavior reinforced by food pellets. This result suggested that the toxin did not interfere generally with motor capacity but rather acted selectively to block morphine reinforcement. Inactivated PTX did not reduce VTA morphine self-administration, thus demonstrating that PTX blockade of opioid reinforcement is primarily due to enzymatic inactivation of inhibitory G-proteins. All these findings are consistent with the hypothesis that inhibitory G-proteins in the hippocampus and VTA mediate the reinforcing effects of opioid drugs.


Monocular deprivation and the signal transmission by X- and Y-neurons of the cat lateral geniculate nucleus.
1. In adult cats deprived monocularly from the second week of life, single neurons were recorded from the optic tract (OT), the lateral geniculate body (pars dorsalis, LGN) and the optic radiation (OR). The neurons were classified according to their visual response properties (Y/X) or their latencies to OT electrical stimulation (class I/II). 2. A close positive correlation (greater than 95%) was found between the visual classification and the latency classification (Y = I, X = II). 3. The relative frequency of class I/Y-neurons was reduced in the group of pattern-deprived LGN neurons, but normal in the pattern-deprived OR neurons. 4. The ratio of the r1 and r2 wave amplitude of the OR-evoked potentials elicited by electrical stimulation of the normal or the deprived eye optic nerve was not affected by pattern deprivation. 5. The activity pattern of neurons recorded from the LGN or the OR did not differ in normal and pattern-deprived neurons belonging to the same class (on-center/off-center; Y/X). The same was true for the neuronal responses to electrical stimulation of the OT at different stimulus frequencies (1-200 stimuli/s). 6. The average maintained activity of pattern-deprived OT or OR neurons recorded while the eyelids of the deprived eye were still closed was either equal to or even somewhat higher than the average activity of the corresponding normal neurons. This was true when the patterned stimuli were presented stationary or were moved at random within the visual field simulating the effect of eye and head movements. The pattern deprivation effects found morphologically and physiologically in the visual cortex are, therefore, not induced by a diminished average activity of the input neurons from the deprived eye.


Methylation state of the human HLA-DRa gene in transgenic mice.
We describe the tissue-specific expression and the reconstitution of the canonical methylation state of the human HLA-DRa gene in transgenic mice.


Simvastatin and oxidative stress in humans: A randomized, double-blinded, placebo-controlled clinical trial.
Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, and thereby reduces the risk of cardiovascular disease. In addition, simvastatin treatment leads to a reduction in fluxes in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species, which have been implicated in the pathogenesis of arteriosclerosis. Therefore, we hypothesized that simvastatin may reduce oxidative stress in humans in vivo. We conducted a randomized, double-blinded, placebo-controlled study in which subjects were treated with either 40mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine and plasma samples. A total of 40 participants were included, of which 39 completed the trial. The observed differences between simvastatin and placebo groups in the primary outcomes, DNA and RNA oxidation, were small and nonsignificant (p=0.68), specifically, 3% in the simvastatin group compared to 7.1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced in parallel with the reduction in plasma cholesterol. In healthy young male volunteers, short-term simvastatin treatment, which considerably reduces cholesterol, does not lead to a clinically relevant reduction in a panel of measures of oxidative stress. Whether simvastatin has effects on oxidative stress in diseased populations, such as diabetes or hemochromatosis, where oxidative stress is prominent, is unknown but seems unlikely.


Searching two or more databases decreased the risk of missing relevant studies: a metaresearch study.
Assessing changes in coverage, recall, review, conclusions and references not found when searching fewer databases. In randomly selected 60 Cochrane reviews, we checked included study publications' coverage (indexation) and recall (findability) using different search approaches with MEDLINE, Embase, and CENTRAL and related them to authors' conclusions and certainty. We assessed characteristics of unfound references. Overall 1989/2080 included references, were indexed in ≥1 database (coverage = 96%). In reviews where using one of our search approaches would not change conclusions and certainty (n = 44-54), median coverage and recall were highest (range 87.9%-100.0% and 78.2%-93.3%, respectively). Here, searching ≥2 databases reached >95% coverage and ≥87.9% recall. In reviews with unchanged conclusions but less certainty (n = 2-8): 63.3%-79.3% coverage and 45.0%-75.0% recall. In reviews with opposite conclusions (n = 1-3): 63.3%-96.6% and 52.1%-78.7%. In reviews where a conclusion was no longer possible (n = 3-7): 60.6%-86.0% and 20.0%-53.8%. The 265 references that were indexed but unfound were more often abstractless (30% vs. 11%) and older (28% vs. 17% published before 1991) than found references. Searching ≥2 databases improves coverage and recall and decreases the risk of missing eligible studies. If researchers suspect that relevant articles are difficult to find, supplementary search methods should be used.


Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.
Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR.


The mechanism of action of a substance P antagonist (D-Pro2, D-Trp7,9)-SP.
1 A newly synthesized substance P (SP) analogue, (D-Pro2, D-Trp7,9)-SP, specifically antagonizes the contractile effects of SP on the guinea-pig isolated taenia coli. In addition, previous studies had indicated that the SP analogue per se is capable of contracting this preparation. The results of the present study on the guinea-pig taenia suggest that the smooth muscle contractions produced by the SP analogue are due to histamine release. No contractions were observed following blockade of histamine H1-receptors by mepyramine or following pretreatment with the histamine liberating agent, compound 48/80. 2 Analysis of the inhibition of SP-induced contraction by the analogue suggests that the inhibition is of the competitive type; pA2 was calculated to be 6.1. 3 We conclude that (D-Pro2, D-Trp7,9)-SP is a competitive SP antagonist with histamine-releasing properties.


Evaluation of the T-scan system in achieving functional masticatory balance.
Uniform occlusal load distribution over the two halves of the dentition is an important factor in achieving a balanced static and functional occlusion. To assess the capacity of the T-scan system in achieving functional masticatory balance using our own method for precise balancing of static and functional occlusal relations in fixed prostheses. The method was designed on the basis of test studies of the T-scan system and a computer program specially developed to measure the occlusal load on films recorded with the T-scan. We used the method to control the static and functional occlusal relationships in 22 patients with a total number of 65 fixed prostheses over a period of 6 years. The control records of occlusal contacts with the T-scan system in all 22 patients as well as the clinical follow-up examinations showed similar values of the occlusal load in the two halves of the dentition. The patients did not have any complaints or feel any discomfort with the prosthetic restorations. The results demonstrated the potential of the T-scan system for achieving functional masticatory balance. The method we designed is proposed as a method of choice if technical resources are available.


A simple and reliable method for purifying glycol methacrylate for histopathological studies.
Pure glycol methacrylate (GMA) is an excellent embedding medium which allows High Performance Optical Microscopic studies. However presence of methacrylic acid (MA) small amounts (usually 1 to 3%) leads to intense background staining of the section. A simple and reliable chemical purification procedure is exposed which leads to an extra-pure GMA free of MA and hydroquinone.


Flight Tunnel Response of Male European Corn Borer Moths to Cross-Specific Mixtures of European and Asian Corn Borer Sex Pheromones: Evidence Supporting a Critical Stage in Evolution of a New Communication System.
Previous flight tunnel studies showed that 3-5 % of male European corn borer (ECB) moths, Ostrinia nubilalis, could fly upwind and make contact with sources releasing the sex pheromone of the closely related Asian corn borer (ACB), Ostrina furnacalis, [2:1 (Z)-12-tetradecenyl acetate (Z12-14:OAc) : (E)-12-teradecenyl acetate (E12-14:OAc)] and that 2-4 % of ACB males could similarly fly upwind to the sex pheromone blends of the ECB Z- [97:3 (Z)-tetradecenyl acetate (Z11-14:OAc) : (E)-tetradecenyl acetate (E11-14:Ac)] and E-strains (1:99 Z/E11-14:OAc) pheromones. The results supported the hypothesis that the evolution of the ACB pheromone system from an ECB-like ancestor included a stage in which males could be attracted to the unusual females emitting Z12- and E12-14:OAc while retaining their responsiveness to the ancestral pheromone blend of Z11- and E11-14:OAc. Here, we showed further that ECB E-strain males exhibited upwind oriented flight and source contacts to sources containing all combinations of ECB and ACB components. Maximal response levels were observed with the E-strain 99:1 E11/Z11-14:OAc blend, and high response levels also were observed with two other blends containing E11-14:OAc as the major component (E11:E12 and E11:Z12). Upwind flight and source contact also occurred at lower levels with the remaining blend combinations in which Z11-, E12-, or Z12-14:OAc was the major component. Our current results support the hypothesis concerning the evolution of ACB from an ECB-like ancester by showing that males were able to respond to females producing either the 12-14:Ac isomers, 11-14:Ac isomers, or even mixtures of all four components.


In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics.
Trace amine-associated receptor-1 (TAAR1) agonists have been proposed as potential antipsychotics, with ulotaront and ralmitaront having reached clinical trials. While ulotaront demonstrated efficacy in a recent Phase II trial, a corresponding study studies of ralmitaront failed to show efficacy as a monotherapy or as an adjunct to atypical antipsychotics. In addition to TAAR1 agonism, ulotaront is a partial agonist at the serotonin 1A receptor (5-HT1AR). However, little is known about ralmitaront. We compared ulotaront and ralmitaront at TAAR1, 5-HT1AR, and dopamine D2 using luciferase complementation-based G protein recruitment, cAMP accumulation, and G protein-coupled inward rectifier potassium channel activation assays. Ralmitaront showed lower efficacy at TAAR1 in G protein recruitment, cAMP accumulation, and GIRK activation assays. Moreover, ralmitaront lacked detectable activity at 5-HT1AR and dopamine D2. Compared with ulotaront, ralmitaront shows lower efficacy and slower kinetics at TAAR1 and lacks efficacy at 5-HT1AR. These data may be relevant to understanding differences in clinical profiles of these 2 compounds.


The heart and hyperthyroidism. Use of beta-adrenergic blocking drugs.
Many of the manifestations of hyperthyroidism are secondary to increased adrenergic activity. In recent years the beta adrenergic blocking drugs, as represented by d,1-propranolol, have become the agents of choice for ameliorating the adrenergic signs and symptoms of hyperthyroidism. Propranolol improves the tachycardia, tremor, restlessness, anxiety, and myopathy.


Breast cancer risk in postmenopausal women using testosterone in combination with hormone replacement therapy.
Testosterone supplementation can be considered as a treatment option for surgically postmenopausal women with a distressful low sexual desire disorder, while on oestrogen therapy with or without progestagens. The purpose of this study is to review the available clinical data on the impact of exogenous testosterone containing postmenopausal hormone therapy on breast cancer risk. A literature search was done in MEDLINE (1969-July 2007) and in addition in EMBASE and Biosis (1990-July 2007) for original reports in English and French. Case reports and studies without a control group were excluded. No prospective randomized clinical trials were found. The five studies found (two case-control studies, two cohort studies and one retrospective observational study) showed inconsistent results. All studies had severe methodological limitations. Formulations and dosages used could be considered suboptimal. At present, there are no valid randomized or observational clinical studies that provide evidence that the addition of testosterone to conventional postmenopausal hormone therapy influences breast cancer risk.


Thymic emigration: conveyor belts or lucky dips?
The thymic medulla has always seemed a rather uncomplicated compartment, simply storing mature thymocytes until they are exported to the peripheral lymphoid organs. However, as discussed here by Roland Scollay and Dale Godfrey, a careful look at recent data suggests that events in the medulla may be more complex and protracted than previously thought.


Effect of C/N ratio and ammonia-N accumulation in a pilot-scale thermophilic dry anaerobic digester.
The effect of ammonia-N accumulation in a dry anaerobic digestion was studied effectively using pilot-scale thermophilic reactor. Two simulations were prepared to attain C/N ratio 27 and C/N ratio 32 using bio-degradable feedstocks such as food waste, fruit and vegetable waste, green waste and paper waste. Organic loading rates and digestate recirculation rates were varied during different time intervals and the performance was evaluated using parameters like pH, VFA, Alkalinity, ammonia-N and biogas yield. Results showed that the simulation with C/N ratio 32 had about 30% less ammonia in digestate as compared to that with C/N ratio 27. The system performed well up to organic loading rate (OLR) 7-10 kgVS/m(3)d and retention time up to 19 days, with surplus energy production of 50-73%. Moreover, a free ammonia accumulation/inhibition effect was documented and methods to overcome the adverse effects were discussed.


Women's expectations and acceptance of cyclic induced HRT bleeds.
To assess women's expectations and acceptance of cyclic induced HRT bleeds before and after their participation in a 1-year study and to compare the impact of these cyclic bleeds with that of previous menstrual bleeds. A structured bleeding questionnaire was used to gather information: at baseline (before screening) on previous menstrual cycle patterns and accompanying discomfort, oral contraceptive use, current smoking habits, parity and the acceptance, preferences and expectations regarding HRT-induced bleeds. Women with amenorrhoea of 6 months or more and FSH levels (35 IU/l then received a daily oral dose of 1 mg 17 beta-oestradiol on days 1-28, combined with either 5 or 10 mg dydrogesterone on days 15-28, for 12 months (13 cycles of 28 days). At the end of their participation, women were again interviewed about their actual experiences with HRT-induced bleeds. One hundred and fifty-four women completed the questionnaire at baseline and 141 (including 131 completers) responded at the end. At baseline, 82% indicated to be pleased that menstruation had ceased, but nevertheless 94% stated that return of periods would be acceptable. At the end, 91% still found the occurrence of cyclic bleeds acceptable; this mostly depended on the perceived benefits outweighing the discomfort. Of the women who actually experienced bleeds (101) 60% regarded discomfort and blood loss less than during their previous menstrual cycles. A regular cycle pattern was considered more important than modest flow and short duration. In contrast to other studies, the acceptance of renewed vaginal bleeds in our study was high.


Determination of haloacetic acids in water by acidic methanol esterification-GC-ECD method.
Acidic methanol esterification followed by gas chromatography (GC) with electron capture detection (ECD) was applied for the determination of the nine haloacetic acids in water. The main advantage of this method is the use of acidic methanol as the derivatization agent instead of the hazardous diazomethane. The recoveries, estimated at concentrations ranging from 0.5 to 30 microg/l, are high for eight of the nine haloacetic acids, with the only exception being monochloroacetic acid. However, problems with this compound have been reported with diazomethane derivatization methods as well. The detection limits of the method range from 0.01 to 0.2 microg/l.


Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep.
The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%, and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2 remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change. Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa; p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.


Residual lymphocele.
Uncomplicated lymphoceles can cause lateral extrinsic compression of the sigmoid colon. Ultrasound is the study of choice to define these cystic collections, which may persist many months as a postoperative complication of pelvic lymph node dissection.


Minimising risk to thoracic surgical teams in an era of COVID-19: exploring possible preventative measures.
The demands of curtailing the impact of the coronavirus disease 2019 (COVID-19) global pandemic have disrupted the world's ability to care for patients with thoracic pathologies. Those who undergo thoracic surgical therapeutic procedures are a high-risk category, likely to have impaired lung function but also high risk for exposing clinical teams to aerosolised viral loads. In light of this global pandemic, thorough pre-procedural planning, adequate personal protective equipment (PPE), experienced personnel and judicious anaesthetic and intra-operative measures will serve to be instrumental in ensuring positive patient outcomes whilst still protecting the safety of healthcare workers.


Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci.
Chromatin accessibility fundamentally governs gene expression and biological response programs that can be manipulated by pathogens. Here we capture dynamic chromatin landscapes of individual B cells during Epstein-Barr virus (EBV) infection. EBV+ cells that exhibit arrest via antiviral sensing and proliferation-linked DNA damage experience global accessibility reduction. Proliferative EBV+ cells develop expression-linked architectures and motif accessibility profiles resembling in vivo germinal center (GC) phenotypes. Remarkably, EBV elicits dark zone (DZ), light zone (LZ), and post-GC B cell chromatin features despite BCL6 downregulation. Integration of single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), single-cell RNA sequencing (scRNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data enables genome-wide cis-regulatory predictions implicating EBV nuclear antigens (EBNAs) in phenotype-specific control of GC B cell activation, survival, and immune evasion. Knockouts validate bioinformatically identified regulators (MEF2C and NFE2L2) of EBV-induced GC phenotypes and EBNA-associated loci that regulate gene expression (CD274/PD-L1). These data and methods can inform high-resolution investigations of EBV-host interactions, B cell fates, and virus-mediated lymphomagenesis.


Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone.
The transition zone (TZ) of primary cilia serves as a diffusion barrier to regulate ciliogenesis and receptor localization for key signaling events such as sonic hedgehog signaling. Its gating mechanism is poorly understood due to the tiny volume accommodating a large number of ciliopathy-associated molecules. Here we performed stimulated emission depletion (STED) imaging of collective samples and recreated superresolved relative localizations of eight representative species of ciliary proteins using position averages and overlapped with representative electron microscopy (EM) images, defining an architectural foundation at the ciliary base. Upon this framework, transmembrane proteins TMEM67 and TCTN2 were accumulated at the same axial level as MKS1 and RPGRIP1L, suggesting that their regulation roles for tissue-specific ciliogenesis occur at a specific level of the TZ. CEP290 is surprisingly localized at a different axial level bridging the basal body (BB) and other TZ proteins. Upon this molecular architecture, two reservoirs of intraflagellar transport (IFT) particles, correlating with phases of ciliary growth, are present: one colocalized with the transition fibers (TFs) while the other situated beyond the distal edge of the TZ. Together, our results reveal an unprecedented structural framework of the TZ, facilitating our understanding in molecular screening and assembly at the ciliary base.


Relationship between soluble transferrin receptor and type 2 diabetes mellitus: A meta-analysis.
Obesity may play a role in the association between sTfR and T2DM. Analysis of the review carried out by Liu et al. titled "Iron metabolism and type 2 diabetes mellitus: A meta-analysis and systematic review".


Optical Coherence Tomography-Guided Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Rationale and Design of the ATLAS-OCT Study.
Even after successful revascularization with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), subsequent adverse events still occur. Previous studies have suggested potential benefits of intravascular imaging, including optical coherence tomography (OCT). However, the feasibility of OCT-guided primary PCI has not been systematically examined in these patients. The ATLAS-OCT (ST-elevation Acute myocardial infarcTion and cLinicAl outcomeS treated by Optical Coherence Tomography-guided percutaneous coronary intervention) trial was designed to investigate the feasibility of OCT guidance during primary PCI for STEMI in experienced centers with expertise on OCT-guided PCI as a prospective, multicenter registry of consecutive patients with STEMI who underwent a primary PCI. The sites' inclusion criteria are as follows: (1) acute care hospitals providing 24/7 emergency care for STEMI, and (2) institutions where OCT-guided PCI is the first choice for primary PCI in STEMI. All patients with STEMI who underwent primary PCI at participating sites will be consecutively enrolled, irrespective of OCT use during PCI. The primary end point will be the rate of successful OCT imaging during the primary PCI. As an ancillary imaging modality to angiography, OCT provides morphologic information during PCI for the assessment of plaque phenotypes, vessel sizing, and PCI optimization. Major adverse cardiac events, defined as a composite of all-cause death, myocardial infarction, and target vessel revascularization at 1 year, will also be recorded. The ATLAS-OCT study will clarify the feasibility of OCT-guided primary PCI for patients with STEMI and further identify a suitable patient group for OCT-guided primary PCI.


The effects of gonadotropin releasing hormone analogue therapy on girls with gonadotropin-dependent precocious puberty.
It has been reported that gonadotropin releasing hormone analogue (GnRHa) therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. The purpose of this study was to evaluate the effect of GnRHa on the adult height of girls with gonadotropin-dependent precocious puberty and the adverse effects of such therapy. Between 1989 and 2006, 11 girls with gonadotropin-dependent precocious puberty who had been treated with GnRHa and reached their adult height were enrolled in the present study. Follow-up studies of bone age, pelvic sonography and GnRH test were done regularly during the period of treatment. All patients had bone mineral density examined at least 2 years after completion of GnRHa therapy. GnRHa therapy was initiated at the age of 8.0 +/- 1.5 years. The predicted adult height immediately before GnRHa therapy was 146.7 +/- 4.8 cm (-2.3 +/- 0.9 standard deviation [SD]). The duration of GnRHa therapy was 4.7 +/- 1.8 years. The adult height of the patients was 156.3 +/- 4.3 cm (-0.6 +/- 0.8 SD), which is similar to their target height of 157.0 +/- 4.5 cm (-0.5 +/- 0.8 SD). The uterine sizes and gonadotropin responses to GnRH stimulation were well suppressed during treatment. Menstruation resumed 9.2 +/- 5.9 months after the discontinuation of treatment in these patients. Forty-five percent of patients had lumbar bone mineral density less than 1 SD below that of normal young Taiwanese adults in the Taipei region. GnRHa therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. However, 45% of patients had decreased bone accretion during therapy.


Interdisciplinary Management of Malignant Ovarian Tumors in the Pediatric and Adolescent Age Group.
Malignant ovarian neoplasms are uncommon in the pediatric and adolescent population. Imaging and tumor markers help to guide the preoperative risk/benefit analysis for planned surgical management, which is the mainstay of therapy. An interdisciplinary approach should be taken in the management of this vulnerable population from diagnosis through post-treatment surveillance. In this review, the initial evaluation, risk stratification, and management of various types of malignant ovarian masses will be addressed, with a special focus on how to optimize an interdisciplinary approach to ovarian masses.


Voltage-Gated Sodium Channel β Subunits and Their Related Diseases.
Voltage-gated sodium channels are protein complexes comprised of one pore forming α subunit and two, non-pore forming, β subunits. The voltage-gated sodium channel β subunits were originally identified to function as auxiliary subunits, which modulate the gating, kinetics, and localization of the ion channel pore. Since that time, the five β subunits have been shown to play crucial roles as multifunctional signaling molecules involved in cell adhesion, cell migration, neuronal pathfinding, fasciculation, and neurite outgrowth. Here, we provide an overview of the evidence implicating the β subunits in their conducting and non-conducting roles. Mutations in the β subunit genes (SCN1B-SCN4B) have been linked to a variety of diseases. These include cancer, epilepsy, cardiac arrhythmias, sudden infant death syndrome/sudden unexpected death in epilepsy, neuropathic pain, and multiple neurodegenerative disorders. β subunits thus provide novel therapeutic targets for future drug discovery.


[Concept and results of the German Research Network on Schizophrenia].
The German Research Network on Schizophrenia (GRNS) was funded by the Federal Ministry of Education and Research (BMBF) from 1999 to 2011. The aim was to obtain a better horizontal and vertical networking of German research and care facilities on schizophrenia, in order to investigate open research questions, to transfer the results into clinical practice and improve care and quality of life in patients with schizophrenia. This paper describes the concept and operations of the GRNS as well as its results on the basis of selected research projects. The GRNS comprised about 25 clinical trials of high practical relevance, which were closely interrelated regarding content, methodology and organization. The trials primarily served the development and evaluation of new and established diagnostic and therapeutic approaches, the assessment of the status quo of clinical care, as well as its improvements, together with the investigation of basic scientific questions. Many substantial results to highly relevant issues were obtained, which led or will lead to an improvement in mental health care. Quantitative and qualitative evaluation parameters, such as scientific publications and obtaining additional grants, as well as promotion of young scientists, public relations activities, congress activities and the foundation of a European Schizophrenia Association, document the successful work of the network. Successful funding requests will allow us to continue cooperative schizophrenia research in Germany as initiated by the GRNS, without necessarily always binding these activities formally to the GRNS.


Metabolomics through the lens of precision cardiovascular medicine.
Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development. Major issues concerning the statistical handling of big data generated by metabolomics, as well as its interpretation, will be briefly addressed. Finally, the need for integration of various omics branches and adopting a multi-omics approach to precision medicine will be discussed.


Associations of miRNA-146a and miRNA-223 with Rheumatoid Arthritis and Their Predictive Values.
To analyze the independent associations of miRNA-146a and miRNA-223 with rheumatoid arthritis (RA) and evaluate their predictive values for RA. A total of 68 RA patients were selected as cases, and meanwhile 68 patients with a traumatic knee condition were selected as controls by matching to the cases according to sex and age at the ratio of 1:1. The independent associations of miRNA-146a and miRNA-223 with RA were identified by binary logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate their predictive values for RA. MiRNA-146a and miRNA-223 expression levels in both synovial tissues and serums were statistically higher in cases than in controls, and their expression levels in serums were not statistically different from those in synovial tissues in both cases and controls. The expression levels of miRNA-146a and miRNA-223 in synovial tissues were independently associated with RA, as well as the expression levels of miRNA-146a and miRNA-223 in serums. The area under curve (AUC) of combination of miRNA-146a and miRNA-223 in synovial tissues for the prediction of RA was 0.910 [95% confidence interval (CI): 0.863-0.962], and the AUC of combination of miRNA-146a and miRNA-223 in serums was 0.904 (95% CI: 0.851-0.957). Their difference was not statistically significant (P=0.873), but the AUC of combination prediction was statistically higher than those of individual predictions (synovial tissues: 0.910 vs 0.773, P=0.005, 0.910 vs 0.788, P=0.009; serums: 0.904 vs 0.766, P=0.005, 0.904 vs 0.784, P=0.011). MiRNA-146a and miRNA-223 in both synovial tissues and serums could be applied in predicting RA, and their combination could elevate the predictive value significantly.


Three components of education in burn care: surgical education, inter-professional education, and mentorship.
Education in burn care can be divided into three main components: surgical education, inter-professional education, e.g. critical care education and mentorship. To date these components have been used in varying degrees in most health institutions and to even lesser extent in burn care. The aim of this paper is to highlight each component and how these have been utilized in other fields to develop teams and foster education, and how they can be translated for burn teams. These ideas are not novel; however, this paper aims to shed light on how these concepts can be implemented in burn care, thus not only improving education, but also enabling recruitment and retention of health care providers in this field.


Depression among regular heroin users: the influence of gender.
The aim of this study was to determine the prevalence of recent (last 12 months) depression in regular young heroin users and to ascertain factors associated with depression in this population, broken down by gender. A sample of 561 participants completed a cross-sectional survey. Eligibility criteria were: age 30 years or younger, and having used heroin for at least 12 days in the last 12 months and at least one day in the last 3 months. Participants were recruited outside of health-care facilities in the cities of Barcelona, Madrid and Seville by targeted sampling and chain referral methods. Depression was assessed using the World Mental Health Composite International Diagnostic Interview. The prevalence of recent depression was 22.3% (35.2% among women and 17.3% among men, p<0.001). In the multivariate analysis, the factors positively associated with recent depression in the whole sample were female gender, age 25 or less, inability to work due to health problems and high risk consumption of alcohol. Among woman, the related variables were age 25 or less, cocaine dependence in the last 12 months, and alcohol consumption in that period. Among men, employment status was the only related variable. Analysis of an overall sample without the gender breakdown may hide important differences in the factors associated with depression in men and women. Both prevention and treatment of depression should rely on specific gender analysis.


The Impact of Clinical Seizure Characteristics on Recognition and Treatment of New-onset Focal Epilepsy in Emergency Departments.
Many people with new-onset focal epilepsy initially seek evaluation in emergency departments (EDs), and treatment decisions in EDs can influence likelihood of seizure recurrence. Using data collected for the Human Epilepsy Project (HEP), we assessed the effect of clinical seizure characteristics on ED clinical management. There were 447 participants with new-onset focal epilepsy seen within 4 months of treatment initiation who were eligible and enrolled in HEP. Seizure calendars and medical records were collected. Based on clinical descriptions, seizures were categorized by semiology according to International League Against Epilepsy (ILAE) classifications as either focal nonmotor or focal motor seizures. Overall, 279 of 447(62%) of participants had presented to an ED prior to or at time of epilepsy diagnosis. A total of 132 of 246 (53%) with initial nonmotor seizures presented to an ED. Of these, eight (6%) presented with a first-lifetime nonmotor seizure. The other 124 (94%) presented after multiple seizures: seven (5%) with multiple nonmotor seizures and 117 (89%) with a first-lifetime motor seizure after having prior nonmotor seizures. A total of 147 of 201 (73%) participants with initial motor seizures presented to an ED. Of these, 134 (92%) presented with a first-lifetime motor seizure and 13 (9%) with multiple motor seizures. There was no difference in the likelihood of antiseizure medication initiation between participants who had multiple prior nonmotor seizures followed by a motor seizure (thereby fulfilling the criterion for an epilepsy diagnosis) versus those presenting with a single lifetime motor seizure (39% vs. 43%). There was no difference in recognition of seizures as the presenting complaint (85% vs. 87%) or whether the participant was admitted or referred to a neurologist (87% vs. 79%). This study contributes to evidence of underrecognition of nonmotor focal seizure semiologies in ED settings, which can support large-scale interventions aimed at improving recognition, specialist consultation, and treatment in ED settings.


Targeting the lncMST-EPRS/HSP90AB1 complex as novel therapeutic strategy for T-2 toxin-induced growth retardation.
Growth retardation is a global public health problem that is highly prevalent especially in low-and middle-income countries, which is closely related to the consumption of grains contaminated with T-2 toxin, a risk for human and animal health. However, the possible targets that can relieve T-2 toxin-induced growth retardation still need to be explored. In the present study, T-2 toxin was used as an environmental exposure factor to induce growth retardation and further explore the regulatory role of lncRNA in growth retardation. The present study systematically characterised the expression profiles of lncRNAs and identified a lncRNA lncMST that is related to growth retardation in T-2 toxin-administered rats. Functionally, lncMST could alleviate cell cycle arrest and apoptosis in T-2 toxin-treated GH3 cells. Mechanistically, lncMST, serve as an inducible chaperone RNA, involved in the paradigm "Chemical-induced stress related growth retardation", through recruiting the EPRS/HSP90AB1 complex to increase HDAC6 expression, thus further alleviating T-2 toxin-induced growth retardation. These findings for the first time demonstrate that the probable therapeutic relationship between lncMST and growth retardation, providing an explanation and therapeutic targets for the pathogenesis of growth retardation.


Proteomic changes in the milk of water buffaloes (Bubalus bubalis) with subclinical mastitis due to intramammary infection by Staphylococcus aureus and by non-aureus staphylococci.
Subclinical mastitis by Staphylococcus aureus (SAU) and by non-aureus staphylococci (NAS) is a major issue in the water buffalo. To understand its impact on milk, 6 quarter samples with >3,000,000 cells/mL (3 SAU-positive and 3 NAS-positive) and 6 culture-negative quarter samples with <50,000 cells/mL were investigated by shotgun proteomics and label-free quantitation. A total of 1530 proteins were identified, of which 152 were significantly changed. SAU was more impacting, with 162 vs 127 differential proteins and higher abundance changes (P < 0.0005). The 119 increased proteins had mostly structural (n = 43, 28.29%) or innate immune defence functions (n = 39, 25.66%) and included vimentin, cathelicidins, histones, S100 and neutrophil granule proteins, haptoglobin, and lysozyme. The 33 decreased proteins were mainly involved in lipid metabolism (n = 13, 59.10%) and included butyrophilin, xanthine dehydrogenase/oxidase, and lipid biosynthetic enzymes. The same biological processes were significantly affected also upon STRING analysis. Cathelicidins were the most increased family, as confirmed by western immunoblotting, with a stronger reactivity in SAU mastitis. S100A8 and haptoglobin were also validated by western immunoblotting. In conclusion, we generated a detailed buffalo milk protein dataset and defined the changes occurring in SAU and NAS mastitis, with potential for improving detection (ProteomeXchange identifier PXD012355).


Multiparametric MR Imaging in the Assessment of Brain Tumors.
Functional MR imaging methods make possible the quantification of dynamic physiologic processes that occur in the brain. Moreover, the use of these advanced imaging techniques in the setting of oncologic treatment of the brain is widely accepted and has found worldwide routine clinical use.


Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells.
miR-124 is a brain-enriched microRNA that plays a crucial role in neural development and has been shown to be down-regulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here, we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and in all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often up-regulated in glioma, as a direct functional target of miR-124. Because SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma cell stem-like traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133(+) cell subpopulation, and stem cell marker (BMI1, Nanog, and Nestin) expression, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal, for the first time, that the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2.


Trehalose administration in C57BL/6N old mice affects healthspan improving motor learning and brain anti-oxidant defences in a sex-dependent fashion: a pilot study.
Aim of this study was to characterize the effects of oral trehalose administration (2%w/v) on healthspan in old mice. Trehalose was administered in drinking water for 1 month to male and female C57BL/6N mice aged 25-months. After behavioral phenotyping (grip strength, beam walking and rotarod tests), autophagy (LC3-II/actin) and oxidative stress were tested in the cerebral cortex and gastrocnemius muscle. The latter parameter was indirectly assessed by evaluating carbonyl groups added to proteins as a result of oxidative reactions, in addition to central levels of NRF2 protein, a transcription factor that regulates the expression of antioxidant enzymes. In comparison with sex-matched controls, trehalose-treated males performed better in motor planning and coordination tasks. This behavioral phenotype was associated with an activation of the ubiquitin-proteasome system, autophagy and antioxidant defences in cerebral cortex. Independently from trehalose administration, females were characterized by better motor performance and showed higher levels of ubiquitinated proteins and NRF2 in cerebral cortex, suggesting an up-regulation of basal antioxidant defences. In conclusion, trehalose was effective in counteracting some aspects of age-related decay, with specific effects in male and female subjects.


Time intervals and patient-level factors in oral cancer diagnostic pathways: An application of the WHO framework in India.
Oral cancer, a leading cancer-site in India, is often detected at advanced stages. We evaluated the time intervals from first symptom to help-seeking and diagnosis among oral cancer patients. In this cross-sectional study, we recruited 226 consecutive oral cancer patients (mean age ( ± SD) 51.9 years ( ± 10.9); 81.9% men; 70.3% advanced stage) registered for diagnosis and treatment, between 2019 and 2021 at a cancer care centre in South India. We used WHO framework and previously standardized tools to record time intervals (appraisal, help-seeking and diagnostic) and baseline characteristics. We utilized multivariable logistic regression models to test the associations between 'prolonged (i.e., over 1 month) time intervals') and patient-level factors to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Over a half of patients presented with prolonged appraisal (60%) and help-seeking intervals (57%), and a third (34%) reported prolonged diagnostic interval. Patients with no formal education, no routine healthcare visits, no self-reported risk factors, and those who did not perceive initial symptoms to be serious were 2-4 times more likely to have prolonged appraisal and help-seeking than the rest. High travel costs and self-decision for visiting healthcare facility prolonged help-seeking. Diagnostic interval was prolonged only among women OR= 2.7 (95% CI: 1.2-6.1)) and in patients whose first doctor's opinion was 'nothing to worry' OR (=7.3 (95% CI: 2.6-20.5)). 'Correct knowledge of cancer' shortened appraisal and help-seeking intervals and 'incorrect knowledge and negative beliefs' prolonged diagnostic interval. Our findings highlight that interventions targeting sociocultural and economic determinants, symptom awareness, sensitizing persons at risk (especially women) and primary care providers might reduce overall time to diagnosis. Further, patients without any known risk factors for oral cancer might be at-risk for prolonged appraisal interval. These might help inform 'pull' strategies for cancer control in India and similar settings.


Development and psychometric evaluation of the Hospital Nurse Interpersonal Empathy Questionnaire.
This study aimed to develop the Hospital Nurse Interpersonal Empathy Questionnaire (HNIEQ) and evaluate its psychometric properties. The primary version of HNIEQ was deductively developed through reviewing the literature, and then, its face and content validity were assessed. For construct validity assessment, 250 hospital nurses were randomly selected from hospitals of Kashan, Iran. Their data were used for exploratory factor analysis. Internal consistency was assessed through Cronbach's α coefficient and questionnaire stability was assessed through test-retest intraclass correlation coefficient. Ceiling and floor effects were also assessed. Data analysis was done via the SPSS program (v. 16.0). The final version of HNIEQ contained 45 items. Exploratory factor analysis revealed a six-factor structure (empathetic and ethical attention, perspective adoption, emotional affectability, altruism, emotion identification and responsivity, and reflection forecasting) for the questionnaire which explained 52.7% of the total variance of its total score. The Cronbach's α coefficient and the intraclass correlation coefficient of HNIEQ were 0.953 and 0.972, respectively. HNIEQ is a valid and reliable instrument for empathy assessment among nurses.


Development of a Victorian Falls and Balance Service Directory.
Falls and fall-related injuries amongst older people continue to be a long-term public health issue. Access to specialist services that target fall prevention has been shown to improve outcomes. This project aimed to develop an online directory of public outpatient and ambulatory falls and balance clinics and programs in Victoria. Environmental scan of existing services and survey of service providers between January and August 2020. Forty-seven community-based and 53 hospital-based falls and balance services across metropolitan (46%) and regional (54%) Victoria registered. The majority of services were programs (70%) targeting exercise and/or education, as opposed to clinics (30%), which focus on diagnosis and developing management plans. Survey responses were collated to develop an online service directory: https://www.nari.net.au/victorian-falls-directory CONCLUSIONS: The Victorian Falls and Balance Service Directory provides a centralised and accessible reference for clinicians and community members regarding available outpatient and ambulatory services that target fall prevention.


Childhood type 1 diabetes may increase the risk of atopic dermatitis.
Epidemiological investigations have examined the association between type 1 diabetes mellitus (T1DM) and atopic disease, but have obtained conflicting results. To analyse the association between T1DM and atopic dermatitis (AD) in a population-based, retrospective cohort study that investigated the hypothesis that childhood T1DM is a risk factor for subsequent AD. From claims data of the National Health Insurance programme of Taiwan, we identified 3386 patients with T1DM newly diagnosed from 1998 to 2011 and 12 725 randomly selected controls without T1DM. These were frequency matched by age, sex and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the AD risk. We used Cox proportional hazards regression models to analyse the risk of AD. The overall incidence rate of AD was 1·40-fold (significantly) higher in the T1DM cohort than in the non-T1DM cohort (3·31 vs. 2·35 per 1000 person years). After adjustment for potential risk factors, the overall risk of AD remained higher in the T1DM cohort [adjusted hazard ratio (HR) 1·76, 95% confidence interval (CI) 1·29-2·39] than in those without T1DM. Compared with the non-T1DM cohort, the patients with T1DM with more emergency room visits (adjusted HR 30·1, 95% CI 18·7-48·5) or hospitalizations (adjusted HR 70·3, 95% CI 45·6-114·5) had a higher risk of subsequent AD. This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.


Bimanual anterior vitrectomy using a 25-gauge high-speed cutter to manage vitreous loss during phacoemulsification.
We examined the usefulness of bimanual anterior vitrectomy with a 25-gauge high-speed cutter and infusion cannula for managing vitreous loss during phacoemulsification. Three eyes underwent phacoemulsification under topical anesthesia, during which, posterior capsule rupture occurred, resulting in vitreous loss and residual nuclear fragments. A 25-gauge high-speed cutter (2,500 cuts/min) and a 25-gauge infusion cannula were inserted into the 3 and 9 o'clock ports. Anterior vitrectomy was performed by employing a bimanual technique. A viscoelastic substance and infusion cannula prevented nuclear fragments from falling into the vitreous. The cutter allowed the easy excision of nuclear fragments and sharp excision of the vitreous. The vitreous incarcerated in the iris at 12 o'clock was removed by manipulating the cutter like a spatula. Bimanual anterior vitrectomy, using a 25-gauge high-speed cutter and infusion cannula, allows effective excision of the lost vitreous, while preserving a closed anterior chamber under topical anesthesia.


Cytoprotective Effect of Echinochrome A in Primary Culture of Pulmonary Fibroblasts from Albino Rats under Conditions of Oxidative Stress.
We studied the effect of echinochrome A on the primary culture of pulmonary fibroblasts under normal conditions and under oxidative stress. Exposure to echinochrome A (100 μM, 6 h) did not affect the production of superoxide radical by fibroblasts, area of their nuclei, and number of nucleoli, but reduced the total area of nucleolar organizer regions against the background of stable proliferative activity of the culture. Two-hour oxidative stress induced by hydrogen peroxide solution (60 μM) increased the generation of superoxide radical, decreased DNA-synthetic activity of fibroblasts, area of fibroblast nuclei, and total area of nucleolar organizer regions. Preliminary administration of echinochrome A significantly attenuated the damaging effect of oxidative stress: the intensity of production of superoxide radicals decreased, DNA-synthetic activity and nucleus area of fibroblasts partially recovered; normalization of the total area of nucleoli was accompanied by an increase in their number.


The network of cytokines, receptors and transcription factors governing the development of dendritic cell subsets.
The pathways leading to the development of different dendritic cell (DC) subsets have long been unclear. In recent years, a number of precursors on the route to DC development, both under steady state and inflammatory conditions, have been described, and the nature of these pathways is becoming clearer. In addition, the development of various knockout mouse models and an in vitro system modelling DC development have revealed the role of numerous cytokines and transcription factors that influence DC development. Here, we review recent findings on the factors important in DC development in the context of the developmental pathways that have been described.


Phosphoproteomic analysis with a solid-phase capture-release-tag approach.
A comprehensive study of global phosphorylation events in biological systems is critical. We report a chemistry-based capture-release-tag method for isolation of complex phospho-Ser/Thr-containing peptides by liquid beta-elimination combined with solid-phase Michael addition. The free thiol groups of 6-(mercapto-acetylamino)-hexanoic acid functionalized resin are used as immobilized Michael donors to capture dehydro-serine/threonine peptides. After an acid-mediated release step, phospho-peptides are labeled with a 6-(2-mercapto-acetylamine)-hexanoic amide tag at phosphorylated sites. We applied this method to analyze the phosphorylation status of microtubule-associated proteins. We find that a CDK5 substrate microtubule-associated protein 2 (MAP2) is phosphorylated on residues that are within a homologous region of Tau. The chemical method corroborates previous results and suggests that Tau and MAP2 may contain a CDK5 phosphorylation motif.


Epidemiological and ultrasonographic investigation of bovine fascioliasis in smallholder production system in Eastern Nile Delta of Egypt.
Regular updating of our knowledge on the epidemiological determinants of bovine fascioliasis is necessary to increase the awareness of the disease's significance and subsequently, improve the control measures. The objectives of this study were (1) to estimate the prevalence of bovine fascioliasis, and identify the association of epidemiological characteristics under traditional householders' production systems, (2) to describe the association between the clinical picture, Fasciola spp. egg count and hepatobiliary ultrasonography findings. In total, 270 faecal samples were examined microscopically for the presence or absence of Fasciola spp. egg, using the sedimentation-flotation method. Copro-positive animals were subjected to ultrasonographic examination. Overall prevalence of copro-positive animals was 27.4% (22.4-33.0%, 95% CI). The final multivariate analysis showed that there was a significant association between fascioliasis and animal species (P < 0.03), and administration of anthelmintic (P < 0.0001). Cattle have a less chance of being positive to Fasciola spp. by 0.55 (95% CI: 0.30 - 0.99) compared to water buffaloes. Administration of anthelmintic to animals on a regular basis decreased the risk of copro-positivity to Fasciola spp by 0.17 (95% CI: 0.07 - 0.36) compared to animals received anthelmintic on an irregular basis. Infected animals having different Fasciola spp. egg burden revealed different clinical symptoms associated with hepatobiliary changes on ultrasonographic examination ranged from normal hepatic parenchyma and bile system in low faecal egg load to hyperechogenic hepatic parenchyma, hyperechogenic with distal shadowing bile duct, and distended gallbladder in high faecal egg load of Fasciola spp. In conclusion, the prevalence of bovine fascioliasis is high under the traditional household's production system. Regular administration of anthelmintic significantly reduces the animal's chance of being copro-positive to Fasciola spp. Ultrasound poses a valuable prognostic technique for assessment of bovine fascioliasis.


Maternal and fetal ultrasonographic characteristics, vulvar temperature, and vaginal mucous impedance as variables associated with the onset of parturition in term and induced pre-term ewes.
The aim of this study was to assess and compare ultrasonographic characteristics of maternal and fetal structures, vulvar temperatures, and vaginal mucous impedance in pregnant ewes in the term parturition group (TPG, n = 15) and induced pre-term parturition group (IPPG; n = 15). All the measurements were taken every 12 h throughout the last gestational week. Maternal and fetal structures and the fetal heart rate (HR) were assessed using ultrasonography. The vulvar temperature and vaginal mucous impedance were determined using a non-contact infrared thermometer, and an electronic estrous detector, respectively. The vulvar temperature was less in the TPG and greater in the IPPG; the end-diastolic velocities (EDVs) of the arteries of the placentome and uterus gradually increased before parturition in the IPPG (P = 0.02, P = 0.02 and P = 0.009, respectively). The placentome shear wave velocity (SWV) was greater in the ewes of the IPPG than TPG 48, 36, and 0 h before parturition (P = 0.001). The following variables were associated with the onset of parturition within the next 12 h in the ewes of the IPPG: resistance index (< 0.54) and EDV (> 0.34 cm/s) of the uterine artery; and vulvar temperature (> 37.3 °C). A fetal kidney SWV of < 1.31 m/s was associated with the onset of parturition in the next 12 h in all the ewes. Results indicate vulvar temperature and certain maternal and fetal factors detected using ultrasonograpy may aid in determining fetal maturity and/or the time of parturition in ewes.


Family-based behavioural intervention programme for obese children: a feasibility study.
To assess a 2-year family-based behavioural intervention programme against child obesity. Single-group pre- and post-intervention feasibility study. Swedish paediatric outpatient care. 26 obese children aged 8.3-12.0 years and their parents who had consented to actively participate in a 2-year intervention. 25 paediatric outpatient group sessions over a 2-year period with parallel groups for children and parents. The basis for the programme was a manual containing instructions for tutor-supervised group sessions with obese children and their parents. The primary outcome measure was change in standardised body mass index between baseline and after 36 months. The secondary outcome measures were change in the waist:height ratio, metabolic parameters and programme adherence. The participants were examined at baseline and after 3, 12 and 24 months of therapy and at follow-up 12 months after completion of the programme. The primary outcome measure, standardised body mass index, declined from a mean of 3.3 (0.7 SD) at baseline to 2.9 (0.7 SD) (p<0.001) at follow-up 12 months after completion of the programme. There was no change in the waist:height ratio. Biomedical markers of blood glucose metabolism and lipid status remained in the normal range. 96% of the families completed the programme. This feasibility study of a 2-year family-based behavioural intervention programme in paediatric outpatient care showed promising results with regard to further weight gain and programme adherence. These findings must be confirmed in a randomised controlled trial with longer follow-up before the intervention programme can be implemented on a larger scale.


Emotional attitudes toward symptoms and inadequate coping strategies are major determinants of patient delay in acute myocardial infarction.
Early reperfusion treatment in acute myocardial infarction (AMI) preserves ventricular function and saves lives. After onset of AMI symptoms, patients often delay for hours until the decision to seek medical help. Of the MI-heart (Myocardial Infarction--HElp seeking And ReacTions) study was to identify factors determining patient decision delay. 739 consecutive patients with confirmed AMI (median age 65.3 years, 30.2% females) were studied after transfer from the intensive care unit. A standardized interview covered AMI symptoms, attitudes toward symptoms, coping strategies, and clinical and sociodemographic variables. Of patients, 93.3% knew an AMI could be deadly. 43.9% of the patients who suspected an AMI, and knew it could be deadly, decided late (> 1 hour) to seek medical help. In univariate analyses, attitudes toward symptoms and coping strategies had the highest impact on a late decision. Stepwise logistic regression identified the following independent contributors to a late decision to seek medical help (relative risk, 95% confidence interval): wanting to wait and see (3.53; 2.32-5.39), not taking symptoms seriously (2.47; 1.64-3.72), not wanting to bother anybody (2.14; 1.29-3.57), symptoms improving at first (2.33; 1.52-3.56), asking others for advice (0.46; 0.30-0.71), taking pain medication (2.01; 1.01-4.03), age > 65 years (1.69; 1.17-2.44), very strong intensity of angina (0.60; 0.42-0.87). Emotional attitudes to AMI symptoms and inadequate coping strategies are the major determinants of patient decision delay. They should be considered as a key factor in patient and public education. Modification of these emotional factors might best be achieved by an individualized approach.


Evolution of magnetic surfboards and spin glass behavior in (Fe1-pGap)2TiO5.
The unusual anisotropy of the spin glass (SG) transition in the pseudobrookite system Fe2TiO5has been interpreted as arising from an induced, van der Waals-like, interaction among magnetic clusters. Here we present susceptibility (χ) and specific heat data (C) for Fe2TiO5diluted with non-magnetic Ga, (Fe1-pGap)2TiO5, for disorder parameterp= 0, 0.11, and 0.42, and elastic neutron scattering data forp= 0.20. A uniform suppression ofTgis observed upon increasingp, along with a value ofχTgthat increases asTgdecreases, i.e.dχ(Tg)/dTg<0We also observeCT∝T2in the low temperature limit. The observed behavior places (Fe1-pGap)2TiO5in the category of a strongly geometrically frustrated SG.


Intersectional Discrimination in HIV Healthcare Settings Among Persons with Diagnosed HIV in the United States, Medical Monitoring Project, 2018-2019.
Experiences with stigma and discrimination in healthcare settings are associated with negative health outcome for persons with HIV (PWH). PWH may experience discrimination due to the intersection of multiple marginalized social identities. Describing these experiences is important for informing interventions and strategies to reduce stigma and discrimination. We report experiences with discrimination in HIV healthcare settings attributed to multiple characteristics, e.g., sexual orientation, race/ethnicity, income, or social class, and/or injection drug use, among a nationally representative sample of persons with diagnosed HIV in the United States using data from the Medical Monitoring Project (MMP). We calculated weighted prevalences and associated 95% confidence intervals for any discrimination and discrimination attributed to multiple characteristics (intersectional discrimination). Among those experiencing discrimination, nearly 1 in 4 persons reported intersectional discrimination, with a higher burden among key populations of focus for HIV prevention and treatment. Discrimination was attributed to HIV status (62.5%), sexual orientation (60.4%), and race/ethnicity (54.3%). Persons who experienced intersectional discrimination were less likely to have a regular HIV care provider, have trust in HIV care or treatment information from healthcare providers, and be antiretroviral treatment or HIV care visit adherent. Future studies should explore methods to operationalize and assess experiences with intersectional stigma and discrimination and use the outcomes to inform qualitative research that provides more context and a deeper understanding of experiences with intersectional discrimination among PWH.


Ecological rules for global species distribution also predict performance variation in Ironman triathletes.
Bergmann's and Allen's rules predict changes in body size and appendage length across temperature gradients for species with broad geographic distributions. Larger bodies and longer limbs facilitate cooling whereas smaller bodies and compact limbs limit heat loss. Although these patterns are highly repeatable (hence "rules" of ecology) the patterns and underlying mechanisms are less-well understood in humans. Here I show that variation in running performance among human male triathletes is consistent with both Bergmann's and Allen's rules. Males (but not females) with relatively larger body size and longer limbs performed better at hot compared to cold race venues and vice-versa. Consistent with results in other taxa, sex-specificity may reflect selection for sexual dimorphism. Results suggest that ecological patterns detected over large-spatial scales may arise from fine-scale variation in locomotor performance.


Face recognition memory deficits and visual object memory performance in patients with schizophrenia and their relatives.
Face recognition memory deficits in schizophrenia are attributed to frontotemporal dysfunction. Biological relatives of patients have similar deficits, suggesting genetic susceptibility. Because the impairment may reflect generalized object memory deficits, the authors evaluated both face and visual object recognition. The Penn Face Memory Test and Visual Object Learning Test were given to 102 patients with schizophrenia, 60 of their biological relatives, and 135 healthy comparison subjects. Significant immediate and delayed face recognition deficits were observed in patients and their relatives. Although patients were more impaired in visual object memory than comparison subjects, relatives were not. Face recognition deficits in patients with schizophrenia and their families are not secondary to generalized object memory deficits and may be an endophenotype reflecting frontotemporal impairment.


Intrapartum ultrasound measurement of the lower uterine segment thickness in parturients with previous scar in labor: a cross-sectional study.
There is a lack of reliable methods to estimate the risk of uterine rupture or dehiscence during a trial of labor in women with previous cesarean sections. This study aimed to assess the lower uterine segment and myometrial thickness by ultrasonography in women with previous cesarean sections during labor and assess their association with the uterine defect. A cross-sectional study was conducted on 161 women in the active phase of labor having one previous cesarean section. The study was conducted et al.-Azhar University Hospital, Assiut City, Egypt, from March 2018 to March 2019. Ultrasound measurements of lower uterine segment thickness and myometrial thickness were conducted by vaginal and abdominal ultrasound by two observers. The correlation of both thicknesses with the uterine defect was analyzed. Uterine defects were reported in 42 women (25.9%), uterine rupture in four women (2.5%), and dehiscence in 38 women (23.5%). The uterine defects were not associated with maternal factors (maternal age, gestational age at labor, body mass index, birth weight, interpregnancy, and inter-delivery interval). Receiver operating curve analysis demonstrated that lower uterine segment thickness was linked with uterine defect, with an area under the curve of 60% (95% CI, 51-70%, P = 0.044). Myometrial thickness was also linked to the uterine defect, with an area under the curve of 61% (95% CI, 52-71%, P = 0.025). Full lower uterine segment thickness of 2.3 mm and myometrial thickness of 1.9 mm were the cutoff value with the best combination of sensitivity and specificity for the uterine defect. Lower uterine segment thickness (OR = 0.49, 95%CI 0.24-0.96) and myometrial thickness (OR = 0.44, 95%CI 0.20-0.94) were significantly associated with the uterine defect. Lower uterine segment thickness (OR = 0.41, 95%CI 0.22-0.76) and myometrial thickness (OR = 0.33, 95%CI 0.16-0.66) were also significantly associated with cesarean section delivery. A lower uterine segment thickness of 2.3 mm and myometrial thickness of 1.9 mm during the first stage of labor are associated with a high risk of uterine defects during a labor trial. These measurements during labor can have a practical application in deciding the mode of delivery in women with previous cesarean sections and might reduce uterine rupture.


The influence of industry sponsorship on the reporting of subgroup analyses within phase III randomised controlled trials in gastrointestinal oncology.
Correct interpretation of subgroup analyses (SGA) is important as it influences selection of therapeutic interventions for patient subsets. The primary aim of our study was to compare reporting of SGA between industry and non-industry sponsored trials. We performed a systematic literature review and extracted data from journal articles (JA) and conference abstracts (CA) published over a decade reporting SGA results of phase III randomised controlled gastrointestinal (GI) oncology trials with patient participants of ≥150. In JA, SGA was reported in 100/145 (69%) trials: 41/54 industry sponsored (76%; 95% confidence interval [CI]: 63-86%) and 59/91 non-industry sponsored (65%; 95% CI: 55-74%) trials (p = 0.16). In CA, SGA was reported in 86/204 (42%) trials: 43/83 industry sponsored (52%; 95% CI: 41-62%) and 43/121 non-industry sponsored (36%; 95% CI: 28-44%) trials (p = 0.02). Number of SGA performed per trial was significantly larger for industry compared to non-industry sponsored trials in both JA (median 6 versus 2, p = 0.003) and CA (median 1 versus 0, p = 0.023). Claims of subgroup effect were made in 52% of trials in JA and 50% in CA, with significant test of interaction evident in only 25% of JA and 16% of CA, with no difference between industry and non-industry trials. Industry sponsored trials with a significant primary end-point reported more SGA (p < 0.001 JA; p = 0.046 CA). Industry sponsored trials reported more SGA. Claimed subgroup effects were often not accompanied by significant interaction test; thus circumspection should be adopted when using SGA to deviate from standard therapeutic decision-making in GI oncology.


Collagen remodelling in rat periodontal tissues: compensation for precursor reutilization confirms rapid turnover of collagen.
Measurement of collagen turnover is complicated by the reutilization of isotopic precursors used to label the collagen. In an earlier study a novel approach was used to circumvent the problems of precursor recycling and unusually short half-lives were determined for collagen in adult rat periodontal tissues (Sodek, 1977). To verify these results we have used an alternate procedure devised by Poole (1971) in which the decay profile for the radiolabelled protein is corrected in accordance with the decay of the radiolabelled precursor. In this manner real half-lives for mature, neutral salt-insoluble collagen were determined as 3 days in the molar periodontal ligament, 6 days in the continuously erupting incisor ligament and approximately 10 days in the lamina propria of the gingiva, compared to apparent half-lives for these tissues of 6, 12 and approximately 20 days, respectively. The values calculated for actual half-lives are, therefore, approximately two-fold faster than values determined without compensating for reutilization, a difference that is in agreement with other protein turnover studies in which the effects of precursor reutilization have been measured. Although the real half-lives determined in this study indicate turnover rates for the periodontal tissues that are slightly slower than reported previously, the relative differences between the tissues in the rates of collagen turnover are similar. Moreover, the study confirms the existence of a remarkably high rate of collagen remodelling in these tissues.


The significance of delayed post-traumatic renal hemorrhage.
An impression is presented pertaining to the significance of delayed recurrent post-traumatic renal hematuria, documented by 3 case reports and an appraisal of relevant data selected from prior reports. Adjunctive features may include prolonged initial hematuria despite acceptable radiographic features, a preponderant relationship to penetrating (knife and low velocity missile) wounds and a tendency to respond temporarily to conservative management.


Use of a human wrist blood pressure monitor for arterial blood pressure measurements in normotensive conscious dogs in comparison to veterinary high-definition oscillometry.
The gold standard in canine blood pressure (BP) measurement is the invasive method; however, non-invasive blood pressure measurement techniques (NIBP) are more commonly used. The lack of small, lightweight, cheap, fast and portable NIBP still remains a point to improve in the emergency setting. A human wrist blood pressure (WBP) device was evaluated in comparison with the veterinary high-definition oscillometry (HDO) in conscious normotensive dogs. Systolic and diastolic BPs were evaluated in two groups of dogs. The bias, the limits of agreement and correlation between variables were calculated. Twenty-five and 36 dogs were, respectively, included in Study No. 1 (dogs weighting ≥10 kg) and 2 (dogs weighting ≥20 kg). In both studies, correlation between the two devices was moderate. A better agreement was displayed for diastolic pressure and poor precision for both systolic and diastolic pressures measurements (as determined by wide limits of agreement). The WBP method underestimated both the systolic and diastolic BP with respect to the HDO method. The inclusion of bigger dogs (Study No. 2) with limb circumference more like to human limb dimension did not improve the agreement between considered methods. The human WBP monitor considered is not suitable to replace the commonly used veterinary HDO for in-clinic BP monitoring in normotensive conscious dogs.


Nicotinamide mononucleotide inhibits oxidative stress-induced damage in a SIRT1/NQO-1-dependent manner.
Oxidative stress causes endothelial dysfunction, which is associated with vascular cellular aging and is causally related to cardiovascular disease pathogenesis. Preclinical studies indicate that a nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide mononucleotide (NMN), alleviates oxidative stress in aged vessels, granting vasoprotective effects. However, the associated cellular mechanism remains largely unclear. In this study, we used human umbilical vein endothelial cells (HUVECs) to demonstrate that NMN inhibits oxidative stress-induced damage by activating the sirtuin 1 (SIRT1)/NAD(P)H: quinone oxidoreductase 1 (NQO-1) axis. We found that NMN inhibited H2O2-induced cytotoxicity and senescence-associated protein expression, such as p16 and p21. Furthermore, NMN prevented H2O2-induced actin cytoskeletal disorganization via inhibiting reactive oxygen species (ROS) production. NMN increased NQO-1 mRNA and protein expression that in turn was abrogated by SIRT1 inhibition, suggesting that NMN-inducible NQO-1 was associated with SIRT1 activity. SIRT1 and NQO-1 inhibition attenuated the inhibitory effect of NMN on H2O2-inducible cytotoxicity, senescence-related protein upregulation, and actin cytoskeletal disorganization. Our findings provide new insights into the mechanism by which NMN exerts protective effects against vascular oxidative stress.


Inhibition of amino acid transport and protein synthesis by HgCl2 and methylmercury in astrocytes: selectivity and reversibility.
The previously reported observation that submicromolar concentrations of HgCl2 inhibit glutamate uptake reversibly in astrocytes, without effect on 2-deoxyglucose uptake, suggested that elemental mercury vapor, which is oxidized to mercuric mercury in the brain, might cause neurodegenerative change through the mediation of glutamate excitotoxicity. Here, selectivity is explored further by measuring the inhibition of other amino acid transporters and protein synthesis as a function of HgCl2 concentration. The properties of MeHgCl were compared under identical conditions, and some morphological correlates of function were examined. Inhibition of amino acid transport by HgCl2 was selective, whereas MeHgCl was nonselective. The 50% inhibitory concentrations of HgCl2 for uptake of alpha-aminoisobutyric acid by system A, uptake of alpha-aminoisobutyric acid or kynurenine by a system L variant, and uptake of gamma-aminobutyric acid were all two- to fourfold greater than that for uptake of glutamate. The submicromolar concentrations of HgCl2 that inhibited glutamate transport also inhibited protein synthesis, but in a rapidly reversible fashion, and elicited only discrete ultrastructural changes (heterochromatin, increased numbers of lysosomal bodies, and increased complexity of cell surface). In contrast, inhibition of protein synthesis by MeHgCl was acutely (1-h) irreversible and became marked only at concentrations higher than those that elicited gross morphologic change in the form of "bleb"-like swellings. The results lend support to the proposed excitotoxic mediation of mercury vapor neurotoxicity and reveal a sharp contrast between the effects of HgCl2 and MeHgCl on astrocytes.


A practical overview of CT and MRI features of developmental, inflammatory, and neoplastic lesions of the sphenoid body and clivus.
The sphenoid bone is an unpaired bone that contributes to the formation of the skull base. Despite the enormous progress in transnasal endoscopic visualisation, imaging techniques remain the cornerstones to characterise any pathological condition arising in this area. In the present review, we offer a bird's-eye view of the developmental, inflammatory, and neoplastic alterations affecting the sphenoid body and clivus, with the aim to propose a practical diagnostic aid for radiologists based on clinico-epidemiological, computed tomography, and magnetic resonance imaging features.


A nonradioactive electrophoretic mobility shift assay for measurement of pregnane X receptor binding activity to CYP3A4 response element.
The electrophoretic mobility shift assay (EMSA) is a method for the study of specific DNA–protein interactions in vitro. The pregnane X receptor (PRX) is a key xenobiotic sensor that regulates the expression of drug-metabolizing enzymes andmany other genes. Radiolabeled ³²P-DNA-probes had been used in studies of PXR-DNA interactions. There is an increasing need for nonradioactive assays, due to the health, safety and environmental issues. In the current study, we present a protocol for the nonradioactive electrophoretic mobility shift assay, allowing studying interactions between human PXR with promoter DNA sequences.


Attenuation of phosphoinositide 3-kinase δ signaling restrains autoimmune disease.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by the production of autoantibodies against nuclear components. Lyn-deficient mice are an excellent animal model of SLE manifesting clinical, pathological and biochemical features seen in the human disease. They develop autoreactive antibodies, glomerulonephritis and show generalized inflammation, and their B cells have a hyperactive phenotype. Since loss of Lyn confers hyper-activation of phosphoinositide 3-kinase (PI3K) signaling, we studied the effect of down-modulating PI3K in Lyn-deficient mice. We found that heterozygous inactivation of the p110δ isoform of PI3K was sufficient to restrain disease in Lyn-deficient mice, leading to significantly decreased autoantibody development and autoimmune-mediated kidney pathology, and improved survival. Intriguingly, haploinsufficiency of p110δ did not dampen signaling in Lyn-deficient B cells. However, plasma cell numbers, serum immunoglobulin titers, inflammation and T cell signaling and activation were significantly moderated in Lyn(-/-)p110δ(+/KD) mice. Importantly, we have shown that haploinsufficiency of p110δ has minor effects on the B cell compartment per se but leads to significant defects in T cell activation and B cell class-switching. These studies suggest that agents targeting p110δ PI3K need not achieve full blockade of the enzyme to be of great benefit in the treatment of SLE.


Does the relative density of periarticular bone influence the failure pattern of intra-articular fractures?
The architecture of joints almost certainly influences the nature of intra-articular fractures, and the concavity is much more likely to fail than the associated convexity. However, local differences in periarticular bone density potentially also plays a critical role. The purpose of this study was to investigate if there was any difference in periarticular bone density in intra-articular fractures between the two opposing joint surfaces, comparing the convexity to the concavity. We retrospectively identified a series of 1003 intra-articular fractures of the hip, knee, and ankle; 129 of these patients had previously undergone CT scanning during their routine clinical assessment. Periarticular bone density was assessed using Hounsfield Units (HU) as a measure of the composite density of the adjacent bone. Bone density was compared between the opposite sides of each joint, to determine if a relationship exists between local bone density and the risk of articular surface fracture. There was a statistically significant difference in density between the two opposing surfaces, with the convexity 19% more dense than the concavity (p=0.0001). The knee exhibited the largest difference (55%), followed by the hip (18%); in the ankle, an inverse relationship was observed, and the concave surface was paradoxically denser (5%). There was no significant difference between those cases where the concavity failed in isolation compared to those where the convexity also failed (p=0.28). When the results were pooled for all three joints, there was a statistically significant higher local bone density demonstrated on the convex side of an intra-articular fracture. However, while this relationship was clearly exhibited in the knee, this was less evident in the other two joints; in the ankle the reverse was true, and the local bone adjacent to the concavity was found to have greater density. This suggests local bone density plays only a minor role in determining the nature of intra-articular fractures.


Antibiotic use in acute cholecystitis: practice patterns in the absence of evidence-based guidelines.
Antibiotics are frequently administered in acute cholecystitis for preoperative prophylaxis or postoperative treatment. The optimal timing, choice, and duration of antibiotics are unclear. We conducted a retrospective review of all cases of acute cholecystitis between 1996 and 2001 at the American University of Beirut Medical Centre. A survey among general surgeons was also performed to describe the pattern of antibiotic prescribing in uncomplicated acute cholecystitis. A MEDLINE search for guidelines for antibiotic use in acute cholecystitis was conducted. The number of cases of acute cholecystitis was 79. The mean duration of postoperative antibiotic therapy was 5 days. There was no correlation between the severity of symptoms, gallbladder description, or positive gallbladder culture and the use of antibiotics postoperatively. Sixty five percent of interviewed surgeons would continue antibiotic therapy postoperatively for 3 or more days. Search of the medical literature failed to provide clear guidelines for antibiotic use in acute cholecystitis. The use of antibiotics in patients with acute cholecystitis is erratic and costly. Prospective studies are needed to better study the effectiveness of a short course of antibiotics in uncomplicated cases. The role of gallbladder culture in guiding antibiotic therapy should be defined as routine cultures add to the cost without evident benefit.


Synthesis of carboxy-polyethylene glycol-amine (CA (PEG)n ) and [1-14 C]-CA (PEG)n via oxa-Michael addition of amino-polyethylene glycols to propiolates vs to acrylates.
Synthesis of carboxy-polyethylene glycol-amine (CA (PEG)n ) via oxa-Michael addition of amino-polyethylene glycols to either acrylates or propiolates was investigated. Compared with the oxa-Michael addition to acrylates, the corresponding addition to propiolates was found to proceed under mild reaction conditions and afford the adducts in high yields from a broad scope of substrates. A two-step efficient and convenient synthesis of benzyl [1-14 C]-propiolate from 14 CO2 was therefore developed and utilized as a common synthon to afford practical and high yielding access to [1-14 C]-CA (PEG)n .


A rapid method for determining the G+C content of bacterial chromosomes by monitoring fluorescence intensity during DNA denaturation in a capillary tube.
A simple and rapid method to determine the G+C content of bacterial chromosomal DNA was developed. It involves determination of Tm by a Light Cycler and calculation of the G+C content by an empirical formula relating Tm to G+C content. Instead of a conventional thermal denaturation method, which monitors the increase of absorbance at 260 nm, thermal denaturation was monitored by the decrease of fluorescence intensity in the presence of SYBR Green 1. In this method, the apparent Tm of DNA was influenced by the concentration of SYBR Green 1, DNA and salt. In addition, when the G+C content was calculated from a linear equation [(mol% G+Cx = mol% G+Cr+1.99(Tmx-Tmr), where x is the unknown organism and y is the reference organism], an error value was introduced among strains with extremely low or high G+C content. Based upon five standards (G+C contents in the range 33-66 mol%), a suitable equation was formulated for the capillary method: mol% G+Cx = mol% G+Cr+1.4652(Tmx-Tmr)+0.0063(Tmx2-Tmr2). To determine the Tm of organisms within this range of G+C contents, Escherichia coli ATCC 11775T was used as a DNA standard and fixed concentrations of SYBR Green 1, sodium citrate and DNA were used. The data from 37 bacterial strains indicated that this equation behaved well. Because it is rapid and simple, it may prove useful for bacterial identification.


Identification and distribution of mycosporine-like amino acids in Brazilian cyanobacteria using ultrahigh-performance liquid chromatography with diode array detection coupled to quadrupole time-of-flight mass spectrometry.
Mycosporine-like amino acids (MAAs) are UV-absorbing compounds produced by fungi, algae, lichens, and cyanobacteria when exposed to UV radiation. These compounds have photoprotective and antioxidant functions and have been widely studied for possible use in sunscreens and anti-aging products. This study aims to identify MAA-producing cyanobacteria with potential application in cosmetics. A method for the identification of MAAs was developed using ultrahigh-performance liquid chromatography with diode array detection coupled to quadrupole time-of-flight mass spectrometry (UHPLC-DAD/QTOFMS). Chromatographic separation was carried out using a Synergi 4 μ Hydro-RP 80A column (150 × 2,0 mm) at 30°C with 0.1% formic acid aqueous solution + 2 mM ammonium formate and acetonitrile/water (8:2) + 0.1% formic acid as a mobile phase. Out of the 69 cyanobacteria studied, 26 strains (37%) synthesized MAAs. Nine different MAAs were identified using UHPLC-DAD/QTOFMS. Iminomycosporines were the major group detected (7 in 9 MAAs). In terms of abundance, the most representative genera for MAA production were heterocyte-forming groups. Oscilatoria sp. CMMA 1600, of homocyte type, produced the greatest diversity of MAAs. The UHPLC-DAD/QTOFMS method is a powerful tool for identification and screening of MAAs in cyanobacterial strains as well as in other organisms such as dinoflagellates, macroalgae, and microalgae. The different cyanobacterial genera isolated from diverse Brazilian biomes and environments are prolific sources of MAAs.


Temporal segregation in North American desert Membracidae.
Three species of Membracidae (Homoptera) have been found to coexist on the creosote bush, Larrea tridentata in the Mojave Desert. The insects are monophagous, univoltine and appear to avoid direct competition by temporal segregation. Multareis cornutus overwinters as slow growing nymphs and the adult population peaks in March. Centrodontus atlas overwinters in the egg stage with rapidly growing nymphs appearing in March while the adult population peaks in June. Multareoides bifurcatus overwinters as adults with the adult population peak in July. Nymphs occur in May-June. The various species have evolved cryptic form and coloration which is associated with phenology of the host plant. It is postulated that this has contributed to the evolution of temporal segregation.


Identification and characterization of VPO1, a new animal heme-containing peroxidase.
Animal heme-containing peroxidases play roles in innate immunity, hormone biosynthesis, and the pathogenesis of inflammatory diseases. Using the peroxidase-like domain of Duox1 as a query, we carried out homology searching of the National Center for Biotechnology Information database. Two novel heme-containing peroxidases were identified in humans and mice. One, termed VPO1 for vascular peroxidase 1, exhibits its highest tissue expression in heart and vascular wall. A second, VPO2, present in humans but not in mice, is 63% identical to VPO1 and is highly expressed in heart. The peroxidase homology region of VPO1 shows 42% identity to myeloperoxidase and 57% identity to the insect peroxidase peroxidasin. A molecular model of the VPO1 peroxidase region reveals a structure very similar to that of known peroxidases, including a conserved heme binding cavity, critical catalytic residues, and a calcium binding site. The absorbance spectra of VPO1 are similar to those of lactoperoxidase, and covalent attachment of the heme to VPO1 protein was demonstrated by chemiluminescent heme staining. VPO1 purified from heart or expressed in HEK cells is catalytically active, with a K(m) for H(2)O(2) of 1.5 mM. When co-expressed in cells, VPO1 can use H(2)O(2) produced by NADPH oxidase enzymes. VPO1 is likely to carry out peroxidative reactions previously attributed exclusively to myeloperoxidase in the vascular system.


Is the sleeve anastomosis a risky technique?
We report 15 free flap transfers using sleeve vascular anastomoses with minor modifications of the original method. There was partial necrosis of one flap and one other required reoperation due to kinking of the feeding artery and not to the method of anastomosis. We believe that the sleeve anastomosis is reliable in clinical microvascular surgery if proper cases are selected. Indications for the method are discussed.


CT in evaluation of the circle of Willis.
The method of visualizing the circle of Willis intentionally on contrast-enhanced CT scan was studied. The incidence of circle of Willis in our series was 86%. Only mild side effects were observed, in 7.5% of cases. CT of 60 proven cerebral aneurysms were reviewed and aneurysm was detected in 57%. This method has the potential to be a noninvasive screening procedure for evaluation of suspected cerebral aneurysm, as well as evaluation of marked arteriosclerosis, occlusion of major arteries, and mass effect of parasellar tumors.


Haemophilia treatment in the United Kingdom from 1969 to 1974.
A study has been made by the Haemophilia Centre Directors of the United Kingdom and Northern Ireland. From 1969 to 1974 2600 patients with haemophilia A and 388 with haemophilia B attended Haemophilia Centres for treatment. Of these patients, 71 are known to have died in the survey period. A record is presented of the amounts and types of therapeutic materials used each year during this time. The incidenceof jaundice and anti-factor VIII and anti-factor IX antibodies was recorded.