Phorbol esters cause sequential activation and deactivation of complement receptors on polymorphonuclear leukocytes.
Phorbol myristate acetate (PMA) exerts a biphasic effect on receptors for C3b and C3bi of human polymorphonuclear leukocytes (PMN). The addition of PMA for 10 min enhances the capacity of these receptors to promote binding and phagocytosis of C3b- and C3bi-coated erythrocytes. Upon additional incubation for 60 min, the capacity of these receptors to bind and ingest ligand-coated erythrocytes decreases to levels below those of resting cells. Although PMA does cause increased expression of cell surface C3b and C3bi receptors, the sequential rise and fall of receptor activity cannot be accounted for by alterations in the number of surface receptors. It appears, rather, that PMA causes qualitative changes in these receptors, first an increase in receptor activity (activation) and then a decrease in receptor activity (deactivation). In contrast with its effects on C3 receptors, PMA causes only a reduction in the capacity of Fc receptors to bind and ingest IgG-coated erythrocytes. Deactivation of Fc receptors also appears to involve a qualitative alteration in receptors, because the binding affinity of soluble immune complexes is sharply reduced upon stimulation of PMN with PMA. To explore the role of phosphorylation in the sequential activation and deactivation of phagocytosis-promoting receptors, we loaded PMN with thiophosphate (thioP). This compound is incorporated into cellular nucleotides and proteins, and the resultant (thio)phosphorylated proteins are resistant to phosphatases. thioP-loaded cells show enhanced receptor activity, suggesting that activation of receptors is mediated by a phosphorylation event. Cells loaded with thioP and treated with PMA for 70 min do not deactivate C3 or Fc receptors, suggesting that the deactivation is the result of a dephosphorylation event.


Single-crystal electron paramagnetic resonance studies of photolyzed oxy- and nitric oxide-cobalt myoglobins.
Low-temperature photodissociation of oxygen from oxy-cobalt myoglobin was studied by single-crystal electron paramagnetic resonance (EPR) spectroscopy at 5 K. The photolyzed oxy-cobalt myoglobin exhibited an EPR spectrum consisting of two nonequivalent sets (species I and II) of the principal values and eigenvectors of the g tensors: g1I = 3.55, g2I = 3.47, and g3I = 2.26 for species I, and g1II = 2.04, g2II = 1.93, and g3II = 1.86 for species II, which resembled neither the deoxy nor the oxy form. Possible models of the photodissociated state of oxy-cobalt myoglobin are proposed by comparison with cobalt porphyrin complexes. The photolyzed product of nitric oxide-cobalt myoglobin exhibited new EPR signals at g = 4.3 and a very broad signal at around g = 2. The principal g values have been determined from the single-crystal EPR measurements: g1 = 4.39, g2 = 4.27, and g3 = 4.00. Analysis of another EPR signal around g = 2 was difficult due to its broadness. Magnetic interactions were observed. An isotropic EPR signal at g = 4.3 suggested a weakly spin-coupled system between cobaltous spin (S = 1/2 or 3/2) and nitric oxide spin (S = 1/2).


Unusual accumulation of sulfated glycosphingolipids in colon cancer cells.
The structures of glycosphingolipids from highly purified colorectal cancer cells and normal colorectal epithelial cells of 16 patients have been analyzed in fine detail (Misonou Y, Shida K, Korekane H, Seki Y, Noura S, Ohue M, Miyamoto Y. 2009. Comprehensive Clinico-Glycomic Study of 16 Colorectal Cancer Specimens: Elucidation of aberrant glycosylation and ts mechanistic causes in colorectal cancer cells. J Proteome Res. 8:2990-3005). Further structural analyses demonstrated that colon cancer cells from two patients accumulated unusual glycosphingolipids which were not observed in either colorectal cancer cells or normal colorectal epithelial cells from the other patients. Mass spectrometry analyses revealed that the unusual structures include sulfated oligosaccharides. The structures of the glycosphingolipids of the cancer cells from these two cases were analyzed by methods which include enzymatic release of carbohydrate moieties, fluorescent labeling with aminopyridine and identification using two-dimensional mapping, enzymatic digestion and mass spectrometry together with methanolysis, and the use of newly synthesized sulfo-fucosylated oligosaccharides as standards. The colon cancer cells from one of the patients demonstrate a variety of oligosaccharides as major components which are sulfated at the C6 position of subterminal GlcNAc and at C3 positions of terminal galactose with or without sialylation or fucosylation. These include 6-sulfo Le(x), 6'-sialyl 6-sulfo lactosamine, and 3'-sialyl 6-sulfo Le(x), in addition to sialylated or fucosylated derivatives of type-1 and type-2 hybrid oligosaccharides. The colon cancer cells from the other patient have two kinds of sulfated oligosaccharides, a 6-sulfo Le(x) structure and a 3'-sulfo Le(x) structure, as minor components. Taking into consideration the clinical features of the two patients, the biological significance of sulfated glycosphingolipids on cancer cells is discussed.


The RIPOST-MI study, assessing remote ischemic perconditioning alone or in combination with local ischemic postconditioning in ST-segment elevation myocardial infarction.
Local ischemic postconditioning (IPost) and remote ischemic perconditioning (RIPer) are promising cardioprotective therapies in ST-elevation myocardial infarction (STEMI). We aimed: (1) to investigate whether RIPer initiated at the catheterization laboratory would reduce infarct size, as measured using serum creatine kinase-MB isoenzyme (CK-MB) release as a surrogate marker; (2) to assess if the combination of RIPer and IPost would provide an additional reduction. Patients (n = 151) were randomly allocated to one of the following groups: (1) control group, percutaneous transluminal coronary angioplasty (PTCA) alone; (2) RIPer group, PTCA combined with RIPer, consisting of three cycles of 5-min inflation and 5-min deflation of an upper-arm blood-pressure cuff initiated before reperfusion; (3) RIPer+IPost group, PTCA combined with RIPer and IPost, consisting of four cycles of 1-min inflation and 1-min deflation of the angioplasty balloon. The CK-MB area under the curve (AUC) over 72 h was reduced in RIPer, and RIPer+IPost groups, by 31 and 29 %, respectively, compared to the Control group; however, CK-MB AUC differences between the three groups were not statistically significant (p = 0.06). Peak CK-MB, CK-MB AUC to area at risk (AAR) ratio, and peak CK-MB level to AAR ratio were all significantly reduced in the RIPer and RIPer+IPost groups, compared to the Control group. On the contrary, none of these parameters was significantly different between RIPer+IPost and RIPer groups. To conclude, starting RIPer therapy immediately prior to revascularization was shown to reduce infarct size in STEMI patients, yet combining this therapy with an IPost strategy did not lead to further decrease in infarct size.


Identification of the odour and chemical composition of alumina refinery air emissions.
Alcoa World Alumina Australia has undertaken comprehensive air emissions monitoring aimed at characterising and quantifying the complete range of emissions to the atmosphere from Bayer refining of alumina at its Western Australian refineries. To the best of our knowledge, this project represents the most complete air emissions inventory of a Bayer refinery conducted in the worldwide alumina industry. It adds considerably to knowledge of air emission factors available for use in emissions estimation required under national pollutant release and transfer registers (NPRTs), such as the Toxic Releases Inventory, USA, and the National Pollutant Inventory, Australia. It also allows the preliminary identification of the key chemical components responsible for characteristic alumina refinery odours and the contribution of these components to the quality, or hedonic tone, of the odours. The strength and acceptability of refinery odours to employees and neighbours appears to be dependent upon where and in what proportion the odorous gases have been emitted from the refineries. This paper presents the results of the programme and develops a basis for classifying the odour properties of the key emission sources in the alumina-refining process.


Technology and building design: initiatives to reduce inpatient falls among the elderly.
This paper offers a narrative exploration of interventions for inpatient falls among the elderly with respect to the design of technology (equipment and furniture) and buildings. Most of the contributory risk factors for inpatient falls among the elderly were identified in the 1950s, but incident and injury rates remain relatively unchanged in the 2000s. Interventions have predominantly focused on staff and organizational changes, for example monitoring (observation) and communication, possibly in response to increased patient privacy (isolation) in single rooms. The clinical response has been to modify the patient by means of medication review, continence management, and impact protectors. This paper considers whether technology and building design have helped or hindered the newly admitted frail and/or confused elderly patient at risk of falling, assuming the provision of good nursing and medical practice (e.g., observation, treatment, and care).


Developing slow-release persulfate candles to treat BTEX contaminated groundwater.
The development of slow-release chemical oxidants for sub-surface remediation is a relatively new technology. Our objective was to develop slow-release persulfate-paraffin candles to treat BTEX-contaminated groundwater. Laboratory-scale candles were prepared by heating and mixing Na(2)S(2)O(8) with paraffin in a 2.25 to 1 ratio (w/w), and then pouring the heated mixture into circular molds that were 2.38 cm long and either 0.71 or 1.27 cm in diameter. Activator candles were prepared with FeSO(4) or zerovalent iron (ZVI) and wax. By treating benzoic acid and BTEX compounds with slow-release persulfate and ZVI candles, we observed rapid transformation of all contaminants. By using (14)C-labeled benzoic acid and benzene, we also confirmed mineralization (conversion to CO2) upon exposure to the candles. As the candles aged and were repeatedly exposed to fresh solutions, contaminant transformation rates slowed and removal rates became more linear (zero-order); this change in transformation kinetics mimicked the observed dissolution rates of the candles. By stacking persulfate and ZVI candles on top of each other in a saturated sand tank (14×14×2.5 cm) and spatially sampling around the candles with time, the dissolution patterns of the candles and zone of influence were determined. Results showed that as the candles dissolved and persulfate and iron diffused out into the sand matrix, benzoic acid or benzene concentrations (C(o)=1 mM) decreased by >90% within 7 d. These results support the use of slow-release persulfate and ZVI candles as a means of treating BTEX compounds in contaminated groundwater.


Agroforestry coffee soils increase the insect-suppressive potential offered by entomopathogenic fungi over full-sun soils: A case proposing a "bait survival technique".
Entomopathogenic fungi are important natural enemies of insects. However, there is little information on the insect-suppressive potential of these fungi and possible effects of farming management on this. Meanwhile, changes in natural landscapes due to agricultural intensification have caused considerable biodiversity loss and consequent decay of ecosystem services. However, the adoption of practices such as agroforestry in agroecosystems can foster abiotic and biotic conditions that conserve biodiversity, consequently restoring the provision of ecosystems services. Here, we assessed the effect of management systems (agroforestry or full-sun) on the pest-suppressive potential of entomopathogenic fungi in Brazilian coffee plantations. We used the insect bait method coupled with survival analyses to assess the speed of kill by entomopathogenic fungi and their presence in soil samples from both farming systems. We found that insects exposed to agroforestry soils died more quickly than insects exposed to full-sun soils. Of the fungi isolated from the bait insects, Metarhizium was found most frequently, followed by Beauveria. Meanwhile, Fusarium was frequently isolated as primary or secondary infections. We propose that the differential survival of insects is indicative of a greater suppressive potential by entomopathogenic fungi in agroforestry, and that this could be promoted by the diversified landscape, microclimatic stability, and reduced soil disturbance in agroforestry systems. Furthermore, our results provide a useful demonstration of the potential use of the insect bait method to investigate pest-suppressive potential through bait insect mortality, and we term this the "bait survival technique."


A Multi-Omic Huntington's Disease Transgenic Sheep-Model Database for Investigating Disease Pathogenesis.
The pathological mechanism of cellular dysfunction and death in Huntington's disease (HD) is not well defined. Our transgenic HD sheep model (OVT73) was generated to investigate these mechanisms and for therapeutic testing. One particular cohort of animals has undergone focused investigation resulting in a large interrelated multi-omic dataset, with statistically significant changes observed comparing OVT73 and control 'omic' profiles and reported in literature. Here we make this dataset publicly available for the advancement of HD pathogenic mechanism discovery. To enable investigation in a user-friendly format, we integrated seven multi-omic datasets from a cohort of 5-year-old OVT73 (n = 6) and control (n = 6) sheep into a single database utilising the programming language R. It includes high-throughput transcriptomic, metabolomic and proteomic data from blood, brain, and other tissues. We present the 'multi-omic' HD sheep database as a queryable web-based platform that can be used by the wider HD research community (https://hdsheep.cer.auckland.ac.nz/). The database is supported with a suite of simple automated statistical analysis functions for rapid exploratory analyses. We present examples of its use that validates the integrity relative to results previously reported. The data may also be downloaded for user determined analysis. We propose the use of this online database as a hypothesis generator and method to confirm/refute findings made from patient samples and alternate model systems, to expand our understanding of HD pathogenesis. Importantly, additional tissue samples are available for further investigation of this cohort.


Socially oriented thinking and the biological stress response: Thinking of friends and family predicts trajectories of salivary cortisol decline.
The cortisol stress response has been related to perceived social support, but previous studies rely on self-reported social support variables. The cortisol recovery phase in particular has been theorized to serve a social coping function, but individual differences in recovery slope have not yet been examined in relation to social coping-relevant indices. This study addressed these gaps by examining the relationship of cortisol trajectories after a socioevaluative task to individual differences in covertly assessed cognitions related to close social relationships. We examined trajectories of cortisol change related to socially oriented thinking, the semi-implicit activation of cognitive representations of friends or family. Young adults (N = 64) gave salivary cortisol samples before and for 45 min after a speech task. Participants' thoughts were sampled repeatedly; the frequency of words related to friends or family was assessed to index socially oriented thinking. A free curve slope intercept latent growth curve model showed excellent fit with the cortisol data. Socially oriented thinking was unrelated to overall magnitude of cortisol response to the task (latent intercept) but predicted the latent cortisol trajectory, independently of cortisol intercept and baseline cortisol levels. Socially oriented thinkers showed more gradual cortisol declines, whereas nonsocially oriented thinkers showed a steeper downslope driven primarily by cortisol changes 45 min after the task. Individual differences in socially oriented thinking may manifest in different rates of biological changes following a performance task.


Laser printing of cells into 3D scaffolds.
One of the most promising approaches in tissue engineering is the application of 3D scaffolds, which provide cell support and guidance in the initial tissue formation stage. The porosity of the scaffold and internal pore organization influence cell migration and play a major role in its biodegradation dynamics, nutrient diffusion and mechanical stability. In order to control cell migration and cellular interactions within the scaffold, novel technologies capable of producing 3D structures in accordance with predefined design are required. The two-photon polymerization (2PP) technique, used in this report for the fabrication of scaffolds, allows the realization of arbitrary 3D structures with submicron spatial resolution. Highly porous 3D scaffolds, produced by 2PP of acrylated poly(ethylene glycol), are seeded with cells by means of laser-induced forward transfer (LIFT). In this laser printing approach, a propulsive force, resulting from laser-induced shock wave, is used to propel individual cells or cell groups from a donor substrate towards the receiver substrate. We demonstrate that with this technique printing of multiple cell types into 3D scaffolds is possible. Combination of LIFT and 2PP provides a route for the realization of 3D multicellular tissue constructs and artificial ECM engineered on the microscale.


Problems of thermonuclease detection for identifying Staphylococcus aureus in blood culture broths.
The detection of thermonuclease by the Oxford strain and eight clinical isolates of Staphylococcus aureus in a variety of bacteriological broths with and without added blood was examined using a toluidine blue-DNA-agar plate method. In Isosensitest, brain-heart infusion, tryptic soy, nutrient and gas-liquid chromatography broths (all of which do not contain liquoid) thermonuclease detection was uncomplicated. In Bactec broths (containing liquoid) detectable thermonuclease activity was greatly reduced in the absence of blood. The addition of 10% blood to the Bactec broths restored the activity. Liquoid was shown to be responsible for the inhibition of thermonuclease activity, and its effect could be neutralised by the addition of blood, albumin, or haemoglobin. In specimens containing no blood, or insufficient blood to neutralise the liquoid in culture broths, more has to be added to prevent false negative reporting of S aureus. This can be done after growth at the time of thermonuclease testing. Clinical consequences of delayed identification of S aureus in routine blood cultures may be serious. The application of the thermonuclease test to blood culture broths is both fast and specific.


Analyte variations in consecutive 24-hour urine collections in children.
The metabolic evaluation of children with nephrolithiasis begins with a 24-h urine collection. For adults, the diagnostic yield increases with consecutive collections; however, little is known regarding the variability of multiple 24-h studies in the pediatric population. We sought to evaluate the variability of consecutive 24-h urine collection in children through a multi-institutional study hypothesizing that compared with a single collection, consecutive 24-h urine collections would reveal a greater degree of clinically useful information in the evaluation of children at risk for nephrolithiasis. Including data from six institutions, we identified children less than 18 years of age considered at risk for recurrent nephrolithiasis, undergoing metabolic evaluation. We evaluated a subset of patients performing two collections with urine creatinine varying by 10% or less during a 7-day period. Discordance between repeat collections based on normative urine chemistry values was evaluated. A total of 733 children met inclusion criteria, and in over a third both urine calcium and urine volume differed by 30% or more between samples. Urine oxalate demonstrated greater variation between collections in children <5 years than among older children (p = 0.030) while variation in other parameters did not differ by age. Discordance between repeat samples based on normative values was most common for urine oxalate (22.5%) and the derived relative supersaturation ratios for both calcium phosphate (25.1%) and calcium oxalate (20.5%). The proportion of discordant samples, based on normative thresholds, as well as variability greater ≥30% and 50%, respectively, are shown in the table. Our analysis indicates that stone risk in as many as one in four children may be misclassified if normative values of only a single 24-h urine are used. In light of these findings, repeat 24-h urine collections prior to targeted intervention to modify stone risk are advised to increase diagnostic yield in children at risk for nephrolithiasis.


Impact of Gender, Age at Onset, and Lifetime Tic Disorders on the Clinical Presentation and Comorbidity Pattern of Obsessive-Compulsive Disorder in Children and Adolescents.
Obsessive-compulsive disorder (OCD) is a heterogeneous disorder; therefore, there is a need for identifying more homogeneous subtypes. This study aimed to examine the clinical characteristics and comorbidity pattern of a large sample of pediatric OCD subjects, and to examine the impact of gender, age at onset, and lifetime tic disorders on the clinical presentation and comorbidity pattern. A total of 110 children and adolescents diagnosed with OCD were assessed using the Kiddle Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL) for psychiatric comorbidity, and a clinical data form was filled out. The cutoff for differentiating prepubertal from adolescent onset was 11 years of age. A total of 83.6% of the subjects had at least one comorbid psychiatric disorder. Oppositional defiant disorder and contamination/somatic obsessions were significantly higher in males (p=0.036 and p=0.03, respectively) than in females. Depressive disorders and religious obsessions were significantly higher in the adolescent-onset group (p=0.02, p=0.05, respectively) whereas disruptive behavior disorders were higher in the prepubertal-onset group (p=0.037). Disruptive behavior disorders were significantly more frequent in the tic (+) group than in tic (-) group (p=0.021). There were differences in the comorbidity pattern and clinical expression between genders and between prepubertal and adolescent-onset cases. Findings of this study supported the introduction of tic-related OCD as a specifier in Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), and the necessity of a detailed assessment of other psychiatric disorders in youth with OCD.


Asymptomatic retained surgical gauze towel diagnosed 32 years after nephrectomy.
Retained surgical gauze is a rare but known problem in patients who have medical history of surgery. Suspicion and evaluation of this rare condition is sometimes very difficult for the clinician because retained surgical sponges can be totally asymptomatic or can hide themselves perfectly in the plain abdominal films. For this reason clinican should excersize high rate of suspicion, should not solely depend upon plain films and should consider more sophisticated examinations like ultrasonography (US) or computerized tomography for the appropriate management of these retained sponges. We present here a very unusual and late presentation of surgically retained gauze which gave a false appearance of a kidney with decreased functional activitity in the excretory urography (EU) 32 years after nephrectomy.


Resolution of disseminated granuloma annulare following isotretinoin therapy.
Disseminated granuloma annulare is often a chronic disorder that may prove refractory to treatment and lead to prolonged cosmetic disfigurement. In a patient with disseminated granuloma annulare that was unresponsive to multiple therapeutic regimens, administration of isotretinoin resulted in rapid clearing of nearly all lesions. To our knowledge this is the first reported case in which this agent was used to treat disseminated granuloma annulare.


HIV interventions affect behavior indirectly: results from the AIDS Community Demonstration Projects.
Behavioral theory informs HIV prevention programs by identifying important predictors of the relevant behavior. Changes in those predictors brought about by program messages should theoretically translate into behavior change. Program evaluation, however, may examine only whether message exposure is associated with behavior change, assuming that if people changed their behavior, the intervention must have effectively changed the determinants. This practice obscures how intervention programs work in the field. We use data from the AIDS Community Demonstration Projects (ACDP) to illustrate this important idea. Earlier research found that the ACDP moved at-risk communities to more consistent condom use with both main and non-main partners. This study demonstrates that these behavioral effects are explained by the ACDP's ability to improve intention and self-efficacy for condom use with both main and non-main partners. We conclude that to understand how HIV prevention programs work, program evaluations need to assess how the intervention affected what it was designed to change: one or more critical behavioral determinants.


Association of the consumption of common drinks with early puberty in both sexes.
We examined the effect of sugar-sweetened beverages (SSB) and common drink intake on pubertal development in both sexes. Data were retrieved from Taiwan Children Health Study, which involved detailed pubertal stage assessments of 2,819 schoolchildren aged 11 years in 2011-2012. Drawings of secondary sexual characteristics and self-reported age at menarche or voice breaking were used to assess pubertal stages. Dietary intake was assessed using a detailed semi-quantitative food frequency questionnaire. Generalized estimating equation modeling was applied to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to represent the effects of each drink on early pubertal development outcomes. In boys, an one cup/day increment of a SSB was associated with earlier voice breaking (β = -0.12; 95% CI = -0.20, -0.04), whereas consuming yogurt (≥2 cups/day) was a protective factor against early puberty (OR = 0.78; 95% CI = 0.73, 0.83). In girls, SSB consumption was associated with increased risk of early puberty in a dose-response manner, and a similar protective effect of yogurt consumption and fermented probiotic drink (≥2 cups/day) against early puberty was observed (OR = 0.96; 95% CI = 0.94, 0.99). Furthermore, the intake of both total sugar and added sugar within SSBs increased risk of early puberty in girls but not in boys. Sugar-sweetened beverages were associated with early puberty, and probiotic drinks appeared to mitigate this link. These findings indicate that the gut-brain axis could play a crucial role in sexual maturation.


Modeling human neural functionality in vitro: three-dimensional culture for dopaminergic differentiation.
Advances in mechanistic knowledge of human neurological disorders have been hindered by the lack of adequate human in vitro models. Three-dimensional (3D) cellular models displaying higher biological relevance are gaining momentum; however, their lack of robustness and scarcity of analytical tools adapted to three dimensions hampers their widespread implementation. Herein we show that human midbrain-derived neural progenitor cells, cultured as 3D neurospheres in stirred culture systems, reproducibly differentiate into complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Moreover, an extensive toolbox of analytical methodologies has been adapted to 3D neural cell models, allowing molecular and phenotypic profiling and interrogation. The generated neurons underwent synaptogenesis and elicit spontaneous Ca(2+) transients. Synaptic vesicle trafficking and release of dopamine in response to depolarizing stimuli was also observed. Under whole-cell current-and-voltage clamp, recordings showed polarized neurons (Vm=-70 mV) and voltage-dependent potassium currents, which included A-type-like currents. Glutamate-induced currents sensitive to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate antagonists revealed the existence of functional glutamate receptors. Molecular and phenotypic profiling showed recapitulation of midbrain patterning events, and remodeling toward increased similarity to human brain features, such as extracellular matrix composition and metabolic signature. We have developed a robust and reproducible human 3D neural cell model, which may be extended to patient-derived induced pluripotent stem cells, broadening the applicability of this model.


Isolated Trapezoid Fracture in a Boxer.
BACKGROUND Trapezoid fractures are very uncommon, accounting for less than 1% of all wrist fractures. Isolated fractures of this bone are even more rare, with just a few reports in the literature. The trapezoid bone has a very stable position within the wrist, forming a relatively immobile joint with the second metacarpal base distally. It is also connected by very strong ligaments to the trapezium, capitate and, scaphoid. Trapezoid fractures occur when a strong bending or axial force is applied to the second metacarpal base. CASE REPORT We present a clinical case of an isolated, non-displaced, trapezoid fracture in a young white male, which was treated with cast immobilization for 4 weeks and physical therapy. Complete functional recovery was achieved 3 months after the injury, without any pain or tenderness. CONCLUSIONS Fractures of the trapezoid bone usually have a good clinical outcome. Nonetheless, we need to be very suspicious about this diagnosis since radiography is apparently normal in almost all such cases and clinical examination results may not be entirely clear.


Biologic Augmentation Reduces the Failure Rate of Meniscal Repair: A Systematic Review and Meta-analysis.
Clinical results after isolated meniscal repair are not always satisfactory, with an overall failure rate of around 25%. To improve the success rate of meniscal repair, different biologic augmentation techniques have been introduced in clinical practice, but their real efficacy is still controversial. To evaluate the safety, clinical results, and failure rate of biologic augmentation techniques for meniscal repair. The hypothesis was that biologic augmentation would improve the results of meniscal repair. Systematic review and meta-analysis of comparative studies. A systematic review of the literature was performed in March 2020 of 3 electronic databases (PubMed, Scopus, and the Cochrane Library) regarding meniscal repair combined with biologic augmentation techniques. Articles combining biologic augmentation with other surgical procedures besides meniscal suture were excluded. The quality of the included studies was assessed using a modified Coleman Methodology Score, and the risk of bias was evaluated using the ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) and the RoB 2.0 (Revised Tool for Risk of Bias in Randomized Trials) for nonrandomized and randomized controlled trials, respectively. A total of 11 studies were included in the qualitative analysis: platelet-rich plasma (PRP) augmentation in 6 comparatives studies, fibrin clot augmentation in 2 case series, and mesenchymal stem cells augmentation in 2 case series and 1 case report. One severe adverse event of septic arthritis was reported for PRP 1 month after surgery. The quality of evidence evaluated with the modified Coleman Methodology Score was low overall. Five studies reporting on 286 patients (111 PRP augmentation, 175 control) were included in the quantitative synthesis. A significantly lower risk of failure was documented in the PRP augmentation group as compared with the control group: 9.9% (4.5%-19.1%) versus 25.7% (12.7%-38.7%) (P < .0005). The literature on biologic meniscal augmentation is recent and scarce. Only a few comparative trials are available, all focusing on the potential of PRP. The meta-analysis documented that PRP is safe and useful in improving the survival rate, with a 9.9% rate of failure versus 25.7% for the control group. Further high-level studies are needed to confirm these findings and identify the most effective biologic augmentation strategy to improve the outcome of meniscal repair.


Thyroliberin stimulates rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate by a phosphodiesterase in rat mammotropic pituitary cells. Evidence for an early Ca2+-independent action.
Thyrotropin-releasing hormone (TRH; thyroliberin) stimulated rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] by a phosphodiesterase (phospholipase C) in GH3 cells, a prolactin-secreting rat pituitary tumour cell line. TRH caused a rapid decrease in the level of PtdIns(4,5)P2 to 60% of control and stimulated a marked transient increase in inositol 1,4,5-trisphosphate, the unique product of phosphodiesteratic hydrolysis of PtdIns(4,5)P2, to a peak of 410% of control at 15 s. TRH also caused decreases in phosphatidylinositol 4-monophosphate (PtdIns4P) and phosphatidylinositol (PtdIns) to 65% and 93% of control at 15 s respectively. Inositol 1,4-bisphosphate was increased to a peak of 450% at 30 s; inositol 1-monophosphate and inositol were not elevated until 30 s and 1 min respectively after TRH addition. To study whether PtdIns(4,5)P2 hydrolysis may be caused by an elevation in cytosolic Ca2+ concentration, the changes induced by TRH in the levels of inositol sugars were compared with the effects of membrane depolarization by high extracellular [K+]. The elevation in cytosolic [Ca2+] induced by K+ depolarization did not change the level of inositol 1,4,5-trisphosphate. These data suggest that phosphodiesteratic hydrolysis of PtdIns(4,5)P2 may be the initial event in TRH stimulation of inositol lipid metabolism in GH3 cells and that PtdIns(4,5)P2 hydrolysis is not stimulated by an elevation in cytosolic Ca2+ concentration. The decreases in PtdIns4P and PtdIns may be due to enhanced conversion of PtdIns into PtdIns4P into PtdIns(4,5)P2 or to their direct hydrolysis by phosphomonoesterases and/or phosphodiesterases. These results are consistent with the hypothesis that TRH-stimulated PtdIns(4,5)P2 breakdown causes Ca2+ mobilization leading to prolactin secretion.


Control and selectivity of photosensitized singlet oxygen production: challenges in complex biological systems.
Singlet molecular oxygen is a reactive oxygen species that plays an important role in a number of biological processes, both as a signalling agent and as an intermediate involved in oxidative degradation reactions. Singlet oxygen is commonly generated by the so-called photosensitization process wherein a light-absorbing molecule, the sensitizer, transfers its energy of excitation to ground-state oxygen to make singlet oxygen. This process forms the basis of photodynamic therapy, for example, where light, a sensitizer, and oxygen are used to initiate cell death and ultimately destroy undesired tissue. Although the photosensitized production of singlet oxygen has been studied and used in biologically pertinent systems for years, the photoinitiated behaviour is often indiscriminate and difficult to control. In this Concept, we discuss new ideas and results in which spatial and temporal control of photosensitized singlet oxygen production can be implemented through the incorporation of the sensitizer into a conjugate system that selectively responds to certain triggers or stimuli.


Motor Function and Perception of Health in Women with Provoked Vestibulodynia.
Provoked vestibulodynia (PVD) is a prevalent and disabling condition in women that may be associated with reduced quality of life and impairment of physical functioning. To investigate whether women with PVD have different motor functions, posture and breathing patterns, and whether they perceive their physical health differently, compared with asymptomatic controls. The Standardized Mensendieck Test (SMT) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were used to assess differences between 35 women with PVD and 35 healthy controls. There were no statistically significant differences in any of the 5 motor domains of the SMT between the women with PVD and those without PVD: standing posture, 4.0 (0.6) vs 5.0 (0.6); gait, 4.7 (0.6) vs 4.8 (0.6); movement, 4.8 (0.8) vs 5.1 (0.6); sitting posture, 4.7 (1.0) vs 4.9 (0.8); respiration, 4.7 (1.0) vs 4.7 (0.9). Women with PVD scored significantly lower in all domains on the SF-36 (adjusted Bonferroni P = .002) except physical functioning. Given the lack of difference in the SF-36 physical functioning domain and in all 5 domains of the SMT between women with PVD and those without PVD, the value of interventions focusing on general physical function is unclear. A study strength is the use of an assessor-blinded case-control design, trained physiotherapists to conduct the tests, and valid and reliable outcome measures. A limitation is the homogeneity of the sample of young nulliparous women, which limits the generalizability of our findings to other study populations. Young nulliparous women with PVD did not score differently from a group of healthy controls on assessment of overall physical functioning or on standing posture, gait, movement, sitting posture, and respiration. However, the score for perception of general health was lower in the women with PVD compared with controls. I. Næss, H.C. Frawley, K. Bø. Motor Function and Perception of Health in Women with Provoked Vestibulodynia. J Sex Med 2019;16:1060-1067.


Reduced dosage of the modifiers of epigenetic reprogramming Dnmt1, Dnmt3L, SmcHD1 and Foxo3a has no detectable effect on mouse telomere length in vivo.
Studies carried out in cultured cells have implicated modifiers of epigenetic reprogramming in the regulation of telomere length, reporting elongation in cells that were null for DNA methyltransferase DNA methyltransferase 1 (Dnmt1), both de novo DNA methyltransferases, Dnmt3a and Dnmt3b or various histone methyltransferases. To investigate this further, we assayed telomere length in whole embryos or adult tissue from mice carrying mutations in four different modifiers of epigenetic reprogramming: Dnmt1, DNA methyltransferase 3-like, structural maintenance of chromosomes hinge domain containing 1, and forkhead box O3a. Terminal restriction fragment analysis was used to compare telomere length in homozygous mutants, heterozygous mutants and wild-type littermates. Contrary to expectation, we did not detect overall lengthening in the mutants, raising questions about the role of epigenetic processes in telomere length in vivo.


CArG, CCAAT, and CCAAT-like protein binding sites in avian retrovirus long terminal repeat enhancers.
A strong enhancer element is located within the long terminal repeats (LTRs) of exogenous, oncogenic avian retroviruses, such as Rous sarcoma virus (RSV) and the avian leukosis viruses. The LTRs of a second class of avian retroviruses, the endogenous viruses (evs), lack detectable enhancer function, a property that correlates with major sequence differences between the LTRs of these two virus groups. Despite this lack of independent enhancer activity, we previously identified sequences in ev LTRs that were able to functionally replace essential enhancer domains from the RSV enhancer with which they share limited sequence similarity. To identify candidate enhancer domains in ev LTRs that are functionally equivalent to those in RSV LTRs, we analyzed and compared ev and RSV LTR-specific DNA-protein interactions. Using this approach, we identified two candidate enhancer domains and one deficiency in ev LTRs. One of the proposed ev enhancer domains was identified as a CArG box, a motif also found upstream of several muscle-specific genes, and as the core sequence of the c-fos serum response element. The RSV LTR contains two CArG motifs, one at a previously identified site and one identified in this report at the same relative location as the ev CArG motif. A second factor binding site that interacts with a heat-stable protein was also identified in ev LTRs and, contrary to previous suggestions, appears to be different from previously described exogenous virus enhancer binding proteins. Finally, a deficiency in factor binding was found within the one inverted CCAAT box in ev LTRs, affirming the importance of sequences that flank CCAAT motifs in factor binding and providing a candidate defect in the ev enhancer.


The learning curve for coil embolization of unruptured intracranial aneurysms.
Several studies have shown that procedural outcomes are better at high-volume institutions, possibly due to greater physician experience (learning) or practice (repetition). Our purpose was to determine whether outcomes for coil embolization improved with the experience of the practitioner, after adjusting for the perceived risk of treatment. We identified all unruptured aneurysms treated with coil embolization at our institution from 1990 through 1997. A clinical nurse specialist abstracted the characteristics from cases that met the entry criteria. Two neurologists independently determined the complications by using definitions established a priori. The influence of experience of the treating-physician on complications was evaluated with univariate and multivariable logistic regression analyses. Sixteen complications occurred in 94 patients (17%) treated with coil embolization. Complications occurred in 53% of the first five cases that each of three physicians treated, and in 10% of later cases (P <.001). After an adjustment for all other predictors, including physician assessment of the risk of the procedure, the odds of a complication decreased with increasing physician experience (odds ratio, 0.69 for every five cases treated; 95% confidence interval: 0.50, 0.96; P=.03). The risk of complications with coil embolization of unruptured aneurysms appears to decrease dramatically with physician experience. Because the physicians in this study were highly experienced in other endovascular techniques at study onset, the rate of learning may not be generalizable to other centers.


[Relation of HLA antigens and myocardial infarction].
Genetic predisposition and chronic inflammation play the leading role in the early stages and in the development of atherosclerosis. Previous studies have shown that substantial amounts of T-lymphocytes are present in both early fatty lesions and advanced fibrous lesions in humans. This observation suggests that HLA antigens may be used as genetic markers for the tendency to coronary artery disease. The aim of our study was to investigate the relation of atherosclerosis and HLA antigens in patients with acute myocardial infarction. Thirty consecutive patients with acute myocardial infarction (15 male, 15 female, aged 54+/-8 years) and 30 subjects (15 male, 15 female, aged 52+/-7 years) without evidence of coronary artery disease--according to physical, fundoscopic, electrocardiographic and radiological examination--were enrolled to the study. Histocompatibility antigens (HLA-AB, -DR, -DQ) were studied with lymphocytotoxicity method. Age, gender, smoking, alcohol consumption, frequency of obesity and diabetes mellitus were similar between the two groups. In patients with myocardial infarction frequency of hypertension, family history and hyperlipidemia were significantly higher than the controls (p < 0.0003, p < 0.0001, p < 0.01 respectively). Frequency of HLA antigens in patients and in controls was 50% and 23% for HLA-A2, 63% and 20% for HLA-DQ4 and 90% and 50% for HA-DQ7. Logistic regression analysis revealed a significant relation with the disease and the presence of these antigens (p = 0.02, p = 0.02 and p = 0.03 respectively). It is concluded that in the Turkish population presence of HLA-A2, HLA-DQ4 ve HLA-DQ7 (3) may be used as genetic markers for the tendency to coronary artery disease.


Vocabulary Growth From 18 to 24 Months of Age in Children With and Without Repaired Cleft Palate.
Purpose This study investigated vocabulary growth from 18 to 24 months of age in young children with repaired cleft palate (CP), children with otitis media, and typically developing (TD) children. In addition, the contributions of factors such as hearing level, middle ear status, size of consonant inventory, maternal education level, and gender to the development of expressive vocabulary were explored. Method Vocabulary size of 40 children with repaired CP, 29 children with otitis media, and 25 TD children was measured using the parent report on MacArthur-Bates Communicative Development Inventories: Words and Sentences (Fenson et al., 2007) at 18 and 24 months of age. All participants underwent sound field audiometry at 12 months of age and tympanometry at 18 months of age. A multiple linear regression with and without covariates was used to model vocabulary growth from 18 to 24 months of age across the 3 groups. Results Children with CP produced a significantly smaller number of words at 24 months of age and showed significantly slower rate of vocabulary growth from 18 to 24 months of age when compared to TD children (p < .05). Although middle ear status was found to predict vocabulary growth from 18 to 24 months of age across the 3 groups (p < .05), the confidence interval was large, suggesting the effect should be interpreted with caution. Conclusions Children with CP showed slower expressive vocabulary growth relative to their age-matched TD peers. Middle ear status may be associated with development of vocabulary skills for some children.


Using community-based research to shape the design and delivery of maternal health services in Northern Nigeria.
Maternal mortality ratios in northern Nigeria are among the worst in the world, over 1,000 per 100,000 live births in 2008, with a very low level and quality of maternity services. In 2009, we carried out a study of the reasons for low utilisation of antenatal and delivery care among women with recent pregnancies, and the socio-cultural beliefs and practices that influenced them. The study included a quantitative survey of 6,882 married women, 119 interviews and 95 focus group discussions with community and local government leaders, traditional birth attendants, women who had attended maternity services and health care providers. Only 26% of the women surveyed had received any antenatal care and only 13% delivered in a facility with a skilled birth attendant for their most recent pregnancy. However, those who had had at least one antenatal consultation were 7.6 times more likely to deliver with a skilled birth attendant. Most pregnant women had little or no contact with the health care system for reasons of custom, lack of perceived need, distance, lack of transport, lack of permission, cost and/or unwillingness to see a male doctor. Based on these findings, we designed and implemented an integrated package of interventions that included upgrading antenatal, delivery and emergency obstetric care; providing training, supervision and support for new midwives in primary health centres and hospitals; and providing information to the community about safe pregnancy and delivery and the use of these services.


Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril.
The aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers. In a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h. The area under the plasma concentration-time curve from 0 h to infinity (AUC0-∞) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC0-∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril. The CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril.


Relationship between resting alpha activity and the ERPs obtained during a highly demanding selective attention task.
In spite of previous reports on the relationship between ongoing EEG and ERPs, there remains a lack of agreement on the nature of their nexuses. The aim of the present study was to evaluate the relationship between resting EEG and the ERP components in two groups of healthy subjects with different levels of performance in a highly demanding selective visual attention task. Young adults were classified according to the amount of their correct responses in the task, into high (HP; averaged hits (AH): 86%) and low performance groups (LP; AH: 59%). EEG was recorded during rest, prior to task performance and absolute (AP) and relative power (RP), as well as inter- (rTER) and intrahemispheric (rTRA) correlation were calculated. ERPs during task performance were also obtained and their amplitude and latency measures were assessed. Results showed that individuals with better behavioral performance had a higher synchronization between both hemispheres during rest as well as higher amplitude and shorter latencies of N2 and P3. Principal Component Analysis revealed that alpha2 AP and RP were inversely related to P2 and N2 latency. Higher values of alpha1 and alpha2 rTER were clustered with higher P3 amplitude and shorter reaction time. In conclusion, the differences in the cortical organization of HP and LP at rest (EEG) seem to be associated to the way the brain reacts during information processing (ERPs).


Nitroreductase: a prodrug-activating enzyme for cancer gene therapy.
1. The prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) is activated by Escherichia coli nitroreductase (NTR) to a potent DNA-crosslinking agent. 2. Virus-mediated expression of NTR in tumour cells sensitizes them to CB1954 in vitro and in vivo, providing the basis for a strategy of cancer gene therapy. 3. A phase I trial of CB1954 in cancer patients has been completed, documenting the pharmacokinetics and establishing an acceptable dose. Subsequent trials of the replication-defective adenovirus CTL102 in patients with resectable tumours have documented expression of NTR in injected colorectal liver metastases, hepatocellular carcinoma, head and neck cancer and prostate cancer. Trials combining CTL102 and CB1954 are underway. 4. An oncolytic (replication-competent) adenovirus vector allowed increased expression of NTR in vitro and in a mouse tumour model, resulting in a greater reduction in tumour growth when combined with CB1954 treatment. 5. Alternative prodrugs may eventually prove superior to CB1954; a nitroaryl phosphoramide mustard prodrug activated by NTR shows a greater therapeutic index than CB1954 in a human ovarian carcinoma. 6. The crystal structure of NTR provided the basis for site-directed mutagenesis, which has identified a number of mutants with improved kinetics of CB1954 activation. These can provide improved cell sensitization to CB1954. Combinations of these are being tested. 7. The basis for a positive selection for improved NTR variants has been demonstrated.


Amyloidosis as a complication of cystic fibrosis.
Amyloidosis appears to be a rare complication of cystic fibrosis. We discuss three patients with amyloidosis complicating cystic fibrosis to add to the six patients previously recorded. The presenting problem was proteinuria in five patients, thyromegaly in three patients, and hepatosplenomegaly in one patient. The progression of proteinuria to nephrotic syndrome and edema occurred in eight of nine patients and portended a very poor prognosis. The kidneys, adrenal glands, spleen, thyroid gland, liver, heart, and bowel were most frequently involved. Renal involvement is a frequent and devastating complication of amyloidosis in patients with cystic fibrosis.


Superoxide-mediated nitration of spinal manganese superoxide dismutase: a novel pathway in N-methyl-D-aspartate-mediated hyperalgesia.
N-methyl-D-aspartate (NMDA) receptors serve prominent roles in vast physio-pathological conditions including hyperalgesia (defined as augmented pain intensity in response to painful stimuli) associated with central sensitization. Using M40403 a synthetic low molecular weight superoxide dismutase mimetic that removes superoxide we show for the first time that this radical plays a key role in NMDA-mediated hyperalgesia. Intrathecal administration of NMDA in rats led to a time-dependent development of thermal hyperalgesia. Removal of superoxide with M40403 abolished NMDA-mediated hyperalgesia, while its inactive congener had no effect. Thus NMDA-mediated hyperalgesic response to heat is mediated through spinal release of superoxide. At time of near-to-maximal hyperalgesia, we observed that spinal endogenous manganese superoxide dismutase (MnSOD), the enzyme that normally keeps superoxide under well-controlled condition was nitrated, as shown by immunoprecipitation. Subsequently and as determined by biochemical analysis, nitration of MnSOD led to its deactivation as shown by the loss of the enzyme's ability to dismute and hence remove superoxide. M40403 by preventing MnSOD nitration restored its activity and inhibited the hyperalgesic response to intrathecal NMDA. Thus, superoxide-mediated nitration and deactivation of spinal MnSOD is a novel pathway of NMDA-mediated spinal hyperalgesia and hence central sensitization since it helps to maintain high levels of superoxide that in turn maintains nociceptive signaling. The broader implication of our findings is that superoxide may contribute to various forms of pain events that are driven by NMDA-receptor activation.


Developing a Diagnostic Bundle for Bronchiectasis in South Korea: A Modified Delphi Consensus Study.
Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea. A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement). The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers. Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.


PHARMACOKINETICS AND CLINICAL EFFECTS OF A SINGLE ORAL DOSE OF TRAZODONE IN THE DOMESTIC GOAT (CAPRA HIRCUS) AS A MODEL FOR WILD RUMINANTS.
Trazodone is an antianxiety medication commonly used in human and veterinary medicine. Stress-related trauma is the leading cause of morbidity and mortality in wild ruminant species. Trazodone could reduce stress and allow safer capture and handling, thus having a positive effect on their welfare. The objective of this study was to describe the clinical effects and pharmacokinetic profile of an oral dose of trazodone in domestic goats (Capra hircus) as a model for wild ruminants. A pilot study using ethograms and accelerometers identified an oral dose of 10 mg/kg as optimal to reduce activity levels. This dose resulted in a 502% increase in time spent sleeping (P=0.0016) and a 623% increase in time spent lying down (P=0.01). Additionally, there were reductions of 72% in time spent grooming (P=0.02), 49% in time spent moving (P=0.01), and 87% in time spent observing (P=0.0002). Activity levels were significantly decreased by 31% for 4 hr following administration (P=0.049). There were no observed adverse effects. Time spent eating or ruminating was not affected by trazodone administration (P > 0.05). The pharmacokinetics of trazodone following a single oral dose of 10 mg/kg in 7 goats was assessed. All animals achieved plasma concentrations over 130 ng/ml, a level considered therapeutic in humans and dogs, for a mean of 6.4 ± 5.0 hr. Mean terminal half-life was 10.55 ± 6.80 hr. All goats achieved maximum concentration within 5-15 min and still had detectable plasma levels at 24 hr. Trazodone appears promising to decrease stress in exotic ruminant species. Further research is warranted to establish its efficacy in other ruminant species and clinical situations.


Lineage sorting accounting for the disassociation between chloroplast and mitochondrial lineages in oaks of southern France.
Dumolin-Lapégue et al. (Mol. Biol. Evol. 15: 1321-1331. 1998) suggested that recurrent inversions of a 4-bp sequence of the mtDNA nad4-1/2 locus due to intramolecular recombination were responsible for the disassociation of chloroplast and mitochondrial genomes of French oaks. Based on their PCR-RFLP (PCR-restriction fragment length polymorphism) data obtained from three noncoding spacers, a minimum spanning network representing the phylogeny of the cpDNA was reconstructed. The mapping of alleles b and c of the mtDNA nad4-1/2 locus on the cpDNA network revealed a nonrandom distribution, which contradicted the expected patterns when repeated, and ongoing inversions had been occurring. The fact that polymorphisms (a mixed c + d type) were mostly restricted to the interior nodes of the network, which represented ancient haplotypes and geographically coincided with probable glacial refugia in southern Europe, agreed with a migrant-pool model. Evidence of a widespread pattern of polymorphism distribution indicated that mtDNA haplotypes were likely to be more ancient than the cpDNA haplotypes. Lineage sorting, due to relative age of cpDNA vs. mtDNA, plus the specific migratory mode, which recruited colonists from a random sample of resource populations during glacial expansion (thereby extending the lineage sorting period, LSP), may have resulted in the disassociation of chloroplast and mitochondrial genomes in oaks.


Liver transplantation for alpha-1-antitrypsin deficiency in children.
Alpha-1-antitrypsin (a1-AT) deficiency is an inborn error of metabolism, which can cause liver disease. The condition is one of the most common genetic disorders in the Caucasian population. Here we review our experience with 21 children suffering from end-stage liver disease due to a1-AT deficiency. All children are PIZZ homozygotes. Nineteen of them initially presented with neonatal jaundice and two with hepatosplenomegaly in childhood. Twenty-five liver transplantations were performed. All children are currently alive at a median followup of 40 months. Liver replacement provides the only definite treatment for children with end-stage liver disease associated with a1-AT deficiency. Excellent results can be achieved by reducing waiting time for transplantation and by early referral to a liver transplant centre.


Intracellular acidification-induced alkali metal cation/H+ exchange in human neutrophils.
Pretreatment of isolated human neutrophils (resting pHi congruent to 7.25 at pHo 7.40) with 30 mM NH4Cl for 30 min leads to an intracellular acidification (pHi congruen to 6.60) when the NH4Cl prepulse is removed. Thereafter, in 140 mM Na+ medium, pHi recovers exponentially with time (initial rate, approximately 0.12 pH/min) to reach the normal resting pHi by approximately 20 min, a process that is accomplished mainly, if not exclusively, though an exchange of internal H+ for external Na+. This Na+/H+ countertransport is stimulated by external Na+ (Km congruent to 21 mM) and by external Li+ (Km congruent to 14 mM), though the maximal transport rate for Na+ is about twice that for Li+. Both Na+ and Li+ compete as substrates for the same translocation sites on the exchange carrier. Other alkali metal cations, such as K+, Rb+, or Cs+, do not promote pHi recovery, owing to an apparent lack of affinity for the carrier. The exchange system is unaffected by ouabain or furosemide, but can be competitively inhibited by the diuretic amiloride (Ki congruent to 8 microM). The influx of Na+ or Li+ is accompanied by an equivalent counter-reflux of H+, indicating a 1:1 stoichiometry for the exchange reaction, a finding consistent with the lack of voltage sensitivity (i.e., electroneutrality) of pHi recovery. These studies indicate that the predominant mechanism in human neutrophils for pHi regulation after intracellular acidification is an amiloride-sensitive alkali metal cation/H+ exchange that shares a number of important features with similar recovery processes in a variety of other mammalian cell types.


Attenuation of oxidation and nitration reactions of peroxynitrite by selenomethionine, selenocystine and ebselen.
The effect of the selenium-containing compounds selenomethionine, selenocystine and ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] on the oxidation of dihydrorhodamine 123 caused by peroxynitrite and on the nitration of 4-hydroxyphenylacetate by peroxynitrite was studied in comparison with their sulphur analogues methionine, cystine and ebsulfur [2-phenyl-1,2-benzisothiazol-3(2H)-one]. The selenocompounds protected dihydrorhodamine 123 from oxidation and 4-hydroxyphenylacetate from nitration more effectively than their sulphur analogues. Sodium selenite exhibited no effect. These observations are corollaries to the recent finding [Roussyn, Briviba, Masumoto and Sies (1996) Arch. Biochem. Biophys. 330, 216-218] that selenium-containing compounds are efficient in protecting against peroxynitrite-induced DNA single-strand breaks.


An improved LC-MS/MS method for the detection of classic and low excretor glutaric acidemia type 1.
Glutaric acidemia type I (GA1) is associated with elevated glutarylcarnitine (C5DC), typically measured as its butylester by acylcarnitine profile analysis using tandem mass spectrometry (MS/MS) and the precursor-product ion pair of m/z 388-85. This method neither distinguishes between C5DC and its isomer 3-hydroxydecanoylcarnitine (C10-OH) nor reliably detects the low-excretor variant of GA1, leading to both false-positive and false-negative results when testing for GA1. To overcome these limitations, we developed an LC-MS/MS method that discriminates C5DC from C10-OH by the use of precursor-product ion pairs specific for butylated C5DC (m/z 388-115) and underivatized C10-OH (m/z 332-85). The C5DC method was validated over the linearity range of 0.025-20 μM with a lower limit of quantification (LOQ) of 0.025 μM. Excellent precision and accuracy were also observed. We tested plasma samples from 10 patients with confirmed GA1 (including 3 with the low-excretor variant), 21 patients with mild elevations of C5DC or C10-OH by routine acylcarnitine analysis for which GA1 ultimately was excluded, and 29 normal controls. By using the m/z 388-115 ion pair, all cases of GA1, including the low-excretor variant, were reliably distinguished from normal controls. By using the m/z 388-85 pair, patients with ambiguous elevations of C5DC or C10-OH demonstrated clearly elevated levels of C10-OH (m/z 332-85) but normal C5DC (m/z 388-115), confirming that the apparent elevation of C5DC is due to interference by C10-OH. Our method results in excellent detection of GA1, including the low-excretor variant, and also provides a means to discriminate C5DC and C10-OH in follow-up testing and routine acylcarnitine studies.


Antioxidant activity of soya hypocotyl tea in humans.
Antioxidative activity of isoflavones has not been shown in humans. Newly-developed isoflavone-rich soya hypocotyl tea contains about 12 mg isoflavones per liter. 15 tea drinkers and 23 control young female students were randomly selected from volunteers, and underwent physical examination, blood chemistry and urinary analysis before and after one month of tea drinking. A three-day dietary record was taken before each physical examination. The tea drinkers showed a lower level of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidyl-ethanolamine hydroperoxide (PEOOH) in the red blood cells and a significant reduction of 8-hydroxydeoxyguanine (8ohdG) in the urine compared to the controls.


Slack resources and quality of primary care.
Research generally shows that greater resource utilization fails to translate into higher-quality healthcare. Organizational slack is defined as extra organizational resources needed to meet demand. Divergent views exist on organizational slack in healthcare. Some investigators view slack negatively because it is wasteful, inefficient, and costly, whereas others view slack positively because it allows flexibility in work practices, expanding available services, and protecting against environmental changes. We tested a curvilinear relationship between organizational slack and care quality. The study setting was primary care clinics (n=568) in the Veterans Health Administration. We examined organizational slack using the patient panel size per clinic capacity ratio and support staff per provider ratio staffing guidelines developed by the Veterans Health Administration. Patient-level measures were influenza vaccinations, continuity of care, and overall quality of care ratings. We obtained 2 independent patient samples with approximately 28,000 and 62,000 observations for the analysis. We used multilevel modeling and examined the linear and quadratic terms for both organizational slack measures. We found a significant curvilinear effect for panel size per clinic capacity for influenza vaccinations and overall quality of care. We also found support staff per provider exhibited a curvilinear effect for continuity of care and influenza vaccinations. Greater available resources led to better care, but at a certain point, additional resources provided minimal quality gains. Our findings highlight the importance of primary care clinic managers monitoring staffing levels. Healthcare systems managing a balanced provider workload and staff-mix may realize better patient care delivery and cost management.


Novel application of quantitative immunoassays for screening seed globulins of cowpea varieties.
Using antibodies raised in rabbits, radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) are standardized for cowpea (var. Pusa Barsati) seed globulins. The RIA, when used to screen three stages of seed development, reveals that maximum globulins are detected at 28 days after flowering. When three different varieties of cowpea are assayed for their globulin content by RIA and ELISA, it is observed that the Bold Grain cowpea has the highest amount of related globulin as compared to two other varieties, namely Pusa Phalgun and Asparagus Bean.


Chronic hyponatremia reduces survival of magnocellular vasopressin and oxytocin neurons after axonal injury.
Axonal injury to hypothalamic magnocellular vasopressin (AVP) and oxytocin (OT) neurons causes degeneration of a substantial subpopulation of these neurons. In this study, we investigated the influence of osmolality on this injury-induced cell death. Normonatremic, chronically hypernatremic, and chronically hyponatremic rats received pituitary stalk compression (SC), which causes degeneration of AVP and OT terminals in the neurohypophysis. Twenty-one days after SC, rats were perfused and hypothalami were serially sectioned and alternately stained for AVP-neurophysin and OT-neurophysin immunoreactivities. Normonatremic and hypernatremic rats exhibited a triphasic pattern of water intake after SC, with peak intakes 3 times higher than those exhibited by sham-operated normonatremic rats. In contrast, hyponatremic SC rats exhibited peak water intakes of 600 ml/24 hr, approximately 9-10 times the water intakes of sham-operated normonatremic rats. In normonatremic rats, SC caused degeneration of 65% of the AVP neuron population in the SON and 73% in the PVN, but only 31% of the OT neuron population in the SON and 35% in the PVN. Similar results were found in hypernatremic rats after SC. However, in hyponatremic rats SC caused degeneration of 97% of the AVP neuron population in the SON and 93% in the PVN, and 90% of the OT neuron population in the SON and 84% in the PVN. Our results, therefore, demonstrate that injury-induced degeneration of magnocellular AVP and OT neurons is markedly exacerbated by chronic hypo-osmolar conditions, but neuronal survival is not enhanced by chronic hyperosmolar conditions.


Same-size donor corneas for myopic keratoconus.
To determine the efficacy of using same-size donor grafts for keratoconus patients with axial myopia. A prospective noncomparative interventional case series was performed on 142 eyes of 136 consecutive keratoconus patients. Penetrating keratoplasty (PKP) was performed by 3 skilled surgeons using the same technique with a single running 10-0 nylon suture. Donor button size was determined by a study protocol, where a same-size donor was used for eyes with an axial length (AXL) longer than 24.50 mm, whereas a 0.25-mm-oversized donor was used for eyes shorter than 24.49 mm. Postoperative spherical equivalent (SE) and incidence of postoperative complications were analyzed. Of the 142 consecutive eyes, 123 eyes were operated according to protocol. The average postoperative SE on last visit was -3.94 +/- 3.21 D, with an average uncorrected visual acuity of 0.28 (0.90 average corrected). Postoperative SE correlated inversely (r = 0.46) with preoperative axial length (AXL) expressed by the equation: SE = -0.15 (AXL)2+6.40 (AXL)-71.82. Graft rejection was observed in 7 eyes (5.7%), and glaucoma in 2 eyes that required surgery. Using same-size donor grafts in keratoconus patients with a long visual axis is a safe and effective procedure in reducing postoperative myopia.


Quality of care assessment for small and sick newborns and young infants in Pakistan: findings from a cross-sectional study.
Pakistan is facing a challenging situation in terms of high newborn mortality rate. Securing pregnancy and delivery care may not bring a substantial reduction in neonatal mortality, unless coupled with the provision of quality inpatient care for small and sick newborns and young infants (NYIs). We undertook this study to assess the availability and quality of newborn care services provided and the readiness of inpatient care for NYIs in Pakistan. We conducted a cross-sectional study across Pakistan from February to June 2019, using a purposive sample of 61% (23) of the 38 sick newborn care units at public sector health care facilities providing inpatient care for small and sick NYIs. We interviewed facility managers and health care providers by using structured questionnaires. We observed facility infrastructure and relevant metrics related to the quality of inpatient care such as types of infant care units and essential equipment, drugs, staffing cadre and facility management practices, quality assurance activities, essential services for small and sick NYI care, discharge planning, and support, quality of NYIs care record, and health information system. Of the 23 facilities assessed, 83% had newborn intensive care units (NICUs), 74% reported Special Care Units (SCUs), and only 44% had Kangaroo Mother Care (KMC) Units. All facilities had at least one paediatrician, 13% had neonatologists and neonatal surgeons each. Around 61 and 13% of the facilities had staff trained in neonatal resuscitation and parental counseling, respectively. About 35% of the facilities monitored nosocomial infection rates, with management and interdisciplinary team meetings reported from 17 and 30% of the facilities respectively preceding the survey. Basic interventions for NYIs were available in 43% of the facilities, only 35% of facilities had system in place to monitor nosocomial infections for NYI care. Most (73%) of reviewed records of NYIs at 1-2 days had information on the birth weight, temperature recording (52%), while only a quarter (25%) of the observed records documented danger signs. Mechanism to support discharge care by having linkages with community workers was present in 13% of the facilities, while only 35% of the facilities have strategies to promote adherence after discharge. Majority (78%) of facilities reported monitoring any newborn/ neonatal care indicators, while none of the sub-units within facilities had consolidated information on stillbirths and neonatal deaths. The study has demonstrated important gaps in the quality of small and sick NYI inpatient care in the country. To avert neonatal mortality in the country, provincial and district governments have to take actions in improving the quality of inpatient care.


Triterpene antioxidants from ganoderma lucidum.
Ganoderma lucidum was studied for its antioxidative activity by bioassay guided isolation in conjunction with in vitro tests. The powdered crude drug was treated with boiling water and the aqueous extract (Ex1) was further separated to obtain terpene and polysaccharide fractions. The two fractions and Ex1 were screened for their antioxidative effect against pyrogallol induced erythrocyte membrane oxidation and Fe (II)-ascorbic acid induced lipid peroxidation. All tested samples showed antioxidative activities in a dose dependent manner and the terpene fraction was found to possess the highest effect compared with the others. Chemical isolation of the terpene fraction resulted in the detection of ganoderic acids A, B, C and D, lucidenic acid B and ganodermanontriol as major ingredients.


Novel systems to study vector-pathogen interactions in malaria.
Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating "de novo" genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.


Microfluidic fabrication of water-in-water (w/w) jets and emulsions.
We demonstrate the generation of water-in-water (w/w) jets and emulsions by combining droplet microfluidics and aqueous two-phase systems (ATPS). The application of ATPS in microfluidics has been hampered by the low interfacial tension between typical aqueous phases. The low tension makes it difficult to form w/w droplets with conventional droplet microfluidic approaches. We show that by mechanically perturbing a stable w/w jet, w/w emulsions can be prepared in a controlled and reproducible fashion. We also characterize the encapsulation ability of w/w emulsions and demonstrate that their encapsulation efficiency can be significantly enhanced by inducing formation of precipitates and gels at the w/w interfaces. Our work suggests a biologically and environmentally friendly platform for droplet microfluidics and establishes the potential of w/w droplet microfluidics for encapsulation-related applications.


Mechanisms of Communication in the Mammalian Circadian Timing System.
24-hour rhythms in physiology and behaviour are organized by a body-wide network of endogenous circadian clocks. In mammals, a central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) integrates external light information to adapt cellular clocks in all tissues and organs to the external light-dark cycle. Together, central and peripheral clocks co-regulate physiological rhythms and functions. In this review, we outline the current knowledge about the routes of communication between the environment, the main pacemakers and the downstream clocks in the body, focusing on what we currently know and what we still need to understand about the communication mechanisms by which centrally and peripherally controlled timing signals coordinate physiological functions and behaviour. We highlight recent findings that shed new light on the internal organization and function of the SCN and neuroendocrine mechanisms mediating clock-to-clock coupling. These findings have implications for our understanding of circadian network entrainment and for potential manipulations of the circadian clock system in therapeutic settings.


Nurse practitioners can effectively deliver pain coping skills training to osteoarthritis patients with chronic pain: A randomized, controlled trial.
A multisite, randomized, controlled clinical effectiveness trial was conducted for osteoarthritis patients with chronic pain of the knee or hip. Adult health nurse practitioners provided a 10-session intervention, pain coping skills training (PCST), in patients' doctors' offices (N=129 patients); the control group received usual care (N=127 patients). Primary outcomes assessed at baseline, posttreatment, 6-month follow-up, and 12-month follow-up were: pain intensity, physical functioning, psychological distress, self-efficacy, catastrophizing, use of coping strategies, and quality of life. Secondary measures included fatigue, social functioning, health satisfaction, and use of pain medication. Methods favoring external validity, consistent with pragmatic, effectiveness research, were utilized. Primary ITT and secondary per-protocol analyses were conducted. Attrition was within the expected range: 11% at posttreatment and 29% at 12-month follow-up; rates did not differ between groups. Omnibus ITT analyses across all assessment points indicated significant improvement for the PCST group compared with the control group for pain intensity, physical functioning, psychological distress, use of pain coping strategies, and self-efficacy, as well as fatigue, satisfaction with health, and reduced use of pain medication. Treatment effects were robust to covariates (demographics and clinical sites). Trends in the outcomes across the assessments were examined. All outcomes, except for self-efficacy, were maintained through the 12-month follow-up; effects for self-efficacy degraded over time. Per-protocol analyses did not yield greater effect sizes. Comparisons of PCST patients who were more vs less treatment adherent suggested greater effectiveness for patients with high adherence. Results support the effectiveness of nurse practitioner delivery of PCST for chronic osteoarthritis pain.


Multiple point mutations affecting the simian virus 40 enhancer.
Enhancers, or activators, dramatically increase the transcriptional activity of certain eukaryotic genes. A series of multiple point mutations affecting the simian virus 40 (SV40) enhancer-activator region were generated in order to define the nucleotide sequence required for this function. Three independent assays provided information leading to the identification of nucleotides essential for enhancer function. One class leads to a decrease in gene expression, while the second completely abolishes functional activity. One critical replacement appears to be the first G (guanine) in a sequence TGGAAAG (T, thymine, A, adenine) located in the 5' region of the 72 base-pair repeat of SV40. Comparison of this sequence with nucleotide sequences in other known enhancers leads to the identification of potential related core elements.


Discovery of true electrochemical reactions for ultrahigh catalyst mass activity in water splitting.
Better understanding of true electrochemical reaction behaviors in electrochemical energy devices has long been desired. It has been assumed so far that the reactions occur across the entire catalyst layer (CL), which is designed and fabricated uniformly with catalysts, conductors of protons and electrons, and pathways for reactants and products. By introducing a state-of-the-art characterization system, a thin, highly tunable liquid/gas diffusion layer (LGDL), and an innovative design of electrochemical proton exchange membrane electrolyzer cells (PEMECs), the electrochemical reactions on both microspatial and microtemporal scales are revealed for the first time. Surprisingly, reactions occur only on the CL adjacent to good electrical conductors. On the basis of these findings, new CL fabrications on the novel LGDLs exhibit more than 50 times higher mass activity than conventional catalyst-coated membranes in PEMECs. This discovery presents an opportunity to enhance the multiphase interfacial effects, maximizing the use of the catalysts and significantly reducing the cost of these devices.


Interneurons in the developing human neocortex.
Cortical interneurons play a crucial role in the functioning of cortical microcircuitry as they provide inhibitory input to projection (pyramidal) neurons. Despite their involvement in various neurological and psychiatric disorders, our knowledge about their development in human cerebral cortex is still incomplete. Here we demonstrate that at the beginning of corticogenesis, at embryonic 5 gestation weeks (gw, Carnegie stage 16) in human, early neurons could be labeled with calretinin, calbindin, and GABA antibodies. These immunolabeled cells show a gradient from the ganglionic eminences (GE) toward the neocortex, suggesting that GE is a well conserved source of early born cortical interneurons from rodents to human. At mid-term (20 gw), however, a subset of calretinin(+) cells proliferates in the cortical subventricular zone (SVZ), suggesting a second set of interneuron progenitors that have neocortical origin. Neuropeptide Y, somatostatin, or parvalbumin cells are sparse in mid-term cerebral cortex. In addition to the early source of cortical interneurons in the GE and later in the neocortical SVZ, other regions, such as the subpial granular layer, may also contribute to the population of human cortical interneurons. In conclusion, our findings from cryosections and previous in vitro results suggest that cortical interneuron progenitor population is more complex in humans relative to rodents. The increased complexity of progenitors is probably evolutionary adaptation necessary for development of the higher brain functions characteristic to humans.


An English-language clinic-based literacy program is effective for a multilingual population.
To assess the effectiveness of a clinic-based pediatric literacy intervention on a multilingual population. Clinic-based literacy interventions are effective among English- and Spanish-speaking children. No data exist for multilingual populations. Pediatric clinic in an urban county hospital. Design/Methods. Reading practices of 2 cross-sectional groups were assessed by standardized interview before and after the intervention. The intervention consisted of waiting-room volunteers reading to children, literacy counseling, and gift of a children's book at each well-child visit from 6 months to 5 years. Outcomes were assessed separately for primary English-speaking and primary non-English-speaking families. The baseline (N=85) and postintervention (N=95) groups were similar with respect to child age and sex, parental education, and length of time in the United States. Fourteen languages were represented in total, the most common being English (41%), Somali (28%), Spanish (9%), Vietnamese (7%), Oromo (3%), and Tigrinyan (3%). Compared with baseline, postintervention respondents were more likely to report reading as a favorite activity for the child (10% vs 25%) and parent (18% vs 40%), to read to their child before bed at least weekly (45% vs 71%), and to possess over 10 children's books at home (49% vs 63%). Among English-speaking families (N=30 baseline, N=40 postintervention), weekly bedtime reading increased (63% to 93%), reading as child's favorite activity increased (7% vs 30%), and reading as the parent's favorite activity to do with child increased (33% vs 58%). The proportion of English-speaking families possessing over 10 books at home and those reading with their children at least weekly showed no difference between the baseline and postintervention groups. Among non-English-speaking families (N=55 baseline, N=55 postintervention), weekly bedtime reading increased (36% vs 56%), reading as the parent's favorite activity increased (11% vs 27%), and the number of families to possess >10 children's books in the home increased (31% vs 49%). Reading as child's favorite activity (13% vs 24%) and weekly book sharing (60% vs 76%) showed nonsignificant trends between the non-English-speaking baseline and postintervention groups. This clinic-based literacy intervention influences home literacy behavior in this multiethnic setting, in both English-speaking and non-English-speaking families. Although efforts should be made to make such programs more appropriate for linguistic minorities, non-English-speaking families do stand to benefit from English-language-oriented programs. literacy, Reach Out and Read, pediatrics, reading, child development.


Anabolic responsiveness of skeletal muscles correlates with androgen receptor protein but not mRNA.
Anabolic effects of androgens on skeletal muscle are well documented, but the physiological and biochemical bases of these effects are poorly understood. Skeletal muscles that differ in their androgen responsiveness can be used to examine these mechanisms. We compared androgen receptor mRNA and protein levels of the rat levator ani, a perineal skeletal muscle that depends on androgens for its normal maintenance and function with that of the rat extensor digitorum longus, a limb muscle that does not require androgens. Western immunoblotting indicated that androgen receptor protein is significantly elevated in the levator ani relative to the extensor digitorum longus. Surprisingly, steady state androgen receptor mRNA levels were equivalent in these muscles, as determined by Northern blot analysis and quantitative RT-PCR. These results suggest that androgen responsiveness of skeletal muscles is determined by the level of androgen receptor protein in a particular muscle and that androgen receptor protein content is regulated by translational or post-translational mechanisms.


Gender differences in the relationships of serum uric acid with fasting serum insulin and plasma glucose in patients without diabetes.
To explore gender differences in the relationship of serum uric acid levels with fasting serum insulin and fasting plasma glucose concentrations among an adult Chinese nondiabetic population in Kinmen, Taiwan. A total of 7,483 nondiabetic subjects (4,265 women, 3,218 men, aged 30 to 89 years) were involved in a community based epidemiologic study. Those with known or newly diagnosed diabetes were excluded. Overnight fasting blood samples were drawn for serum uric acid, glucose, insulin, lipid, and other biochemical measurements. Demographic and clinical variables including body mass index (weight/height2), waist-to-hip ratio, and blood pressure were measured and documented during face-to-face interviews with structured questionnaires. Stratified analyses revealed that (1) serum uric acid levels were positively associated with hyperinsulinemia and HOMA-insulin resistance in both men and women after adjusting for hypertriglyceridemia, hypertension, obesity, and plasma glucose levels; and (2) serum uric acid levels were more strongly associated with hyperinsulinemia and plasma glucose levels in women than in men. CONCLUSION; Hyperuricemia was positively associated with hyperinsulinemia among patients of both sexes without diabetes. Elevated levels of uric acid should alert physicians to the possibility of insulin resistance. The serum uric acid level was associated with insulin resistance and plasma glucose levels more strongly in females than in males in our study population.


HIV vulnerability among adolescent girls and young women: a multi-country latent class analysis approach.
To stem the HIV epidemic among adolescent girls and young women (AGYW, 15-24 years), prevention programs need to reach AGYW who are most at risk. We examine whether individual- and household-level factors could be used to define HIV vulnerability for AGYW. We surveyed out-of-school AGYW in urban and peri-urban Kenya (N = 1014), in urban Zambia (N = 846), and in rural Malawi (N = 1654) from October 2016 to 2017. LCA identified classes based on respondent characteristics, attitudes and knowledge, and household characteristics. Multilevel regressions examined associations between class membership and HIV-related health outcomes. We identified two latent classes-high and low HIV vulnerability profiles-among AGYW in each country; 32% of the sample in Kenya, 53% in Malawi, and 51% in Zambia belonged to the high vulnerability group. As compared to AGYW with a low-vulnerability profile, AGYW with a high-vulnerability profile had significantly higher odds of HIV-related outcomes (e.g., very early sexual debut, transactional sex, sexual violence from partners). Out-of-school AGYW had differential vulnerability to HIV. Interventions should focus on reaching AGYW in the high HIV vulnerability profiles.


Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, Longitudinal Single Subject Analysis and Automated Delivery of Individualized Guidance.
Fibromyalgia (FM) is a complex chronic pain condition that is difficult to treat. The prevailing approach is an integration of pharmacological, psycho-educational, and behavioral strategies. Information technology offers great potential for FM sufferers to systemically monitor symptoms as well as potential impacts of various management strategies. This study aimed to evaluate effects of a web-based, self-monitoring and symptom management system (SMARTLog) that analyzes personal self-monitoring data and delivers data-based feedback over time. Subjects were self-referred, anonymous, and recruited via publicity on FM advocacy websites. Standardized instruments assessed health status, self-efficacy, and locus of control at baseline and monthly during participation. Subjects were encouraged to complete the SMARTLog several times weekly. Within-subject, univariate, and multivariate analyses were used to derive classification trees for each user associating specific behavior variables with symptom levels over time. Moderate use (3 times weekly x 3 months) increased likelihood of clinically significant improvements in pain, memory, gastrointestinal problems, depression, fatigue, and concentration; heavy use (4.5 times weekly x five months) produced the above plus improvement in stiffness and sleep difficulties. Individualized, web-based behavioral self-monitoring with personally-tailored feedback can enable FM sufferers to significantly reduce symptom levels over time.


Factors Associated With Black Men's Preference for Health Information.
Black men are less likely to seek routine health care examinations or preventative care compared with their racial/ethnic and gender counterparts. Because of Black men's limited engagement with the health system, Black men's preference to receive health information is unclear. Guided by a revised version of the Andersen Healthcare Utilization Model, the aim of the study is to examine factors associated with Black men's preference for informal or formal health information. Findings from the study demonstrate that financial barriers to care (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43-0.98) and higher income (OR = 2.44, 95% CI = 1.49-4.00) were most predictive of using a formal source for health information. Furthermore, age (OR = 1.02, 95% CI = 1.01-1.03) and having a college education (OR = 0.44, 95% CI = 0.26-0.76) were associated with using a formal place for health information. Interestingly, health care discrimination was not associated with preferred source or place for health information. Results from the study suggest that predisposing and enabling factors are most salient to the use of formal sources of health information among Black men.


Detection of herpesvirus DNA in the serum of immunocompetent children.
The DNA of herpesviruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV6), and human herpesvirus-7 (HHV7) has been detected in the serum of patients with primary infection or with immunosuppression. However, it is unknown how frequently herpesvirus DNA can be detected in the serum of immunocompetent children, or whether the detection of herpesvirus DNA indicates an active infection or virus-related diseases. Using a real-time polymerase chain reaction assay, attempts were made to detect herpesvirus DNA in the serum of 176 ambulatory children who visited a hospital for various reasons. EBV was detected in 4 (2.2%), HHV6 in 4 (2.2%), and HHV7 in 2 (1.1%) of 176 children, but CMV was not detected. Of the 10 positive patients, only 4 were considered, by virtue of clinical and serological characteristics, to have primary infections. The other 4 positive patients had other infections, such as mycoplasma and salmonella. Although herpesvirus DNA could be detected in the serum of immunocompetent children, there was not always a relationship between clinical manifestations and the detection of virus DNA. When herpesvirus DNA is detected in the serum, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease.


Reliability and validity of the Turkish version of ABILHAND-Kids' questionnaire in a group of patients with neuromuscular disorders.
This study was performed to examine the reliability and validity of the Turkish version of ABILHAND-Kids questionnaire which assesses manual functions of children with neuromuscular diseases (NMDs). A cross sectional survey study design and Rasch analysis were used to assess the reliability and validity of the Turkish version of scale. Ninety-three children with different neuromuscular disorders and their parents were included in the study. The scale was applied to the parents with face-to-face interview twice; on their first visit and after an interval of 15 days. The test-retest reliability was assessed with intraclass correlation coefficient (ICC), and internal consistency of the multi-item subscales by calculating Cronbach alpha values. Brooke Upper Extremity Functional Classification (BUEFC) and Wee-Functional Independency Measurement (Wee-FIM) were correlated to determine the construct validity. The ICC value for the test/retest reliability was 0.94. The internal consistency was 0.81. Floor (1.1%) and ceiling (11.8%) effects were not significant. There were moderate correlations between the Turkish version of ABILHAND-Kids and Wee-FIM (0.67) and BUEFC (-0.37). Rasch analysis indicated good item fit, unidimensionality, and model fit. The Turkish version of ABILHAND-Kids questionnaire was found to be a reliable and valid scale for the assessment of the manual ability of children with NMDs.