Mid- to late Holocene sea-level rise recorded in Hells Bells 234U/238U ratio and geochemical composition.
Hells Bells are underwater secondary carbonates discovered in sinkholes (cenotes) southeast of Cancun on the north-eastern Yucatán peninsula, Mexico. These authigenic calcite precipitates, reaching a length of up to 4 m, most likely grow in the pelagic redoxcline. Here we report on detailed 230Th/U-dating and in-depth geochemical and stable isotope analyses of specimens from cenotes El Zapote, Maravilla and Tortugas. Hells Bells developed since at least ~ 8000 years ago, with active growth until present day. Initial (234U/238U) activity ratios (δ234U0) in Hells Bells calcite decreas from 55 to 15‰ as sea level converges toward its present state. The temporal evolution of the geochemistry and isotope composition of Hells Bells calcites thus appears to be closely linked to sea-level rise and reflects changing hydrological conditions (desalinization) of the aquifer. We suggest that decelerated leaching of excess 234U from the previously unsaturated bedrock traces Holocene relative sea-level rise. Considering this proxy, the resulting mean sea-level reconstruction contains half as much scatter, i.e. improves by a factor of two, when compared to previously published work for the period between 8 and 4 ky BP.


Mathieu and Barcat repair with a V incision sutured meatoplasty for secondary hypospadias surgery.
Today single-stage methods are more frequently selected for hypospadias repair than multistaged methods, but complications cannot always be avoided. We employed two kinds of meatal based flip-flap urethroplasty procedures for those with an unsuccessful primary hypospadias repair. From 1997 to 2005, a meatal based flip-flap urethroplasty was performed as a secondary hypospadias surgery on 17 patients. Basically we attempted the Mathieu repair, but when the wings of the glans were not generously widened and the urethral groove was not sufficiently deep we applied the Barcat procedure. While 11 patients were repaired with the Mathieu technique, six patients underwent the Barcat repair. The V incision sutured meatoplasty was added to obtain a natural ventral slit-like meatus. Ten of the 11 patients who underwent the Mathieu repair had a good outcome, but one patient developed a urethrocutaneous fistula. None of the six patients repaired with the Barcat procedure encountered postoperative complications. Cosmetically, a vertical slit was constructed near the normal neomeatus with the Mathieu and V incision sutured (MAVIS) meatoplasty and the Barcat and V incision sutured (BAVIS) meatoplasty. The Mathieu or the Barcat meatal based flip-flap urethroplasty procedure is feasible as a salvage surgery for those with relatively short urethral defects and adequate mobile ventral skin if an exact procedure is selected. Excellent cosmetic results could be obtained by adding the technique of V incision sutured meatoplasty.


Cyclic Fatigue Resistance of Rotary and Reciprocating Nickel-Titanium Instruments Subjected to Static and Dynamic Tests.
This study compared the static and dynamic cyclic fatigue resistance of contemporary nickel-titanium instruments with different kinematic, metallurgic, and design features to establish whether the fatigue-reducing effect of the pecking motion differs among different nickel-titanium instruments. ProTaper Gold (PTG), Hyflex EDM (EDM), Reciproc Blue (RPB), and WaveOne Gold (WOG) files were divided into 2 groups of 10 for the static and dynamic cyclic fatigue resistance tests. A stainless steel artificial canal with 1.5-mm inner diameter, 60° angulation, and 3-mm radius of curvature was used. In the dynamic cyclic fatigue resistance test, speeds were set at 100 and 200 mm/min for the descending and ascending motion, respectively. The number of cycles to fracture (NCF) was calculated, the fractured lengths were recorded, and fractographic analysis of the fractured surfaces was carried out by scanning electron microscopy. Data were analyzed statistically with the Kruskal-Wallis test with Bonferroni correction (alpha = 0.05). The RPB and EDM showed significantly higher NCF in the static and dynamic cyclic fatigue resistance tests (P < .05). The dynamic cyclic fatigue resistance test showed significantly higher NCF than the static cyclic fatigue resistance test in the PTG and EDM (P < .05). There was no significant difference between the RPB and WOG (P > .05). In the experimental condition where the ascending speed was higher than the descending speed, the dynamic cyclic fatigue resistance was significantly higher than the static cyclic fatigue resistance in continuous rotary instruments, but not in reciprocating instruments.


The migration of femoral components after total hip replacement surgery: accuracy and precision of software-aided measurements.
To assess the accuracy and precision of a software-aided system to measure migration of femoral components after total hip replacement (THR) on digitised radiographs. Subsidence and varus-valgus tilt of THR stems within the femur were measured on digitised anteroposterior pelvic radiographs. The measuring software (UMA, GEMED, Germany) relies on bony landmarks and comparability parameters of two consecutive radiographs. Its accuracy and precision were calculated by comparing it with the gold standard in migration measurements, radiostereometric analysis (RSA). Radiographs and corresponding RSA measurements were performed in 60 patients (38-69 years) following cementless THR surgery. The UMA software measured the subsidence of the stems with an accuracy of +/-2.5 mm and varus-valgus tilt with an accuracy of +/-1.8 degrees (95% confidence interval). A good interobserver and intraobserver reliability was calculated with Cronbach's alpha ranging from 0.86 to 0.97. Measuring the subsidence of THR stems within the femur is an important parameter in the diagnosis of implant loosening. Software systems such as UMA improve the accuracy of migration measurements and are easy to use on routinely performed radiographs of operated hip joints.


The ability to self-tickle following Rapid Eye Movement sleep dreaming.
Self-produced tactile stimulation usually feels less tickly--is perceptually attenuated--relative to the same stimulation produced externally. This is not true, however, for individuals with schizophrenia. Here, we investigate whether the lack of attenuation to self-produced stimuli seen in schizophrenia also occurs for normal participants following REM dreams. Fourteen participants were stimulated on their left palm with a tactile stimulation device which allowed the same stimulus to be generated by the participant or by the experimenter. The level of self-tickling attenuation did not differ between REM and non-REM sleep awakening conditions, where presence or absence of an accompanying dream was not controlled for. However, for the female participants, when awakening occurred from an REM sleep dream, self-stimulation ratings were higher than for external stimulation, whereas ratings after NREM sleep unaccompanied by a dream were lower for self-stimulation than for external stimulation. These results indicate deficits in self-monitoring and a confusion between self- and externally generated stimulation accompany REM dream formation.


In vivo activity of the dual PI3Kδ and PI3Kγ inhibitor duvelisib against pediatric acute lymphoblastic leukemia xenografts.
Acute lymphoblastic leukemia (ALL) remains one of the most common causes of cancer-related mortality in children. Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases, and aberrations in the PI3K pathway are associated with several hematological malignancies, including ALL. Duvelisib (Copiktra) is an orally available, small molecule dual inhibitor of PI3Kδ and PI3Kγ, that is Food and Drug Administration (FDA) approved for the treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. Here, we report the efficacy of duvelisib against a panel of pediatric ALL patient-derived xenografts (PDXs). Thirty PDXs were selected for a single mouse trial based on PI3Kδ (PIK3CD) and PI3Kγ (PIK3CG) expression and mutational status. PDXs were grown orthotopically in NSG (NOD.Cg-Prkdcscid IL2rgtm1Wjl /SzJAusb) mice, and engraftment was evaluated by enumerating the proportion of human versus mouse CD45+ cells (%huCD45+ ) in the peripheral blood. Treatment commenced when the %huCD45+ reached greater than or equal to 1%, and events were predefined as %huCD45+ greater than or equal to 25% or leukemia-related morbidity. Duvelisib was administered per oral (50 mg/kg, twice daily for 28 days). Drug efficacy was assessed by event-free survival and stringent objective response measures. PI3Kδ and PI3Kγ mRNA expression was significantly higher in B-lineage than T-lineage ALL PDXs (p-values <.0001). Duvelisib was well-tolerated and reduced leukemia cells in the peripheral blood in four PDXs, but with only one objective response. There was no obvious relationship between duvelisib efficacy and PI3Kδ or PI3Kγ expression or mutation status, nor was the in vivo response to duvelisib subtype dependent. Duvelisib demonstrated limited in vivo activity against ALL PDXs.


Leydig cell death in rats exposed to bismuth subnitrate.
In a previous study, rats were treated with one injection of 500 mg kg(-1) bismuth subnitrate intraperitoneally and maintained for 2 weeks. Bismuth was observed in Leydig cells, with a subsequent reduction in serum testosterone levels. In the present study, stereological procedures were used to estimate the number of Leydig cells in the right testis from the retained rats used in the previously published study. The mean number of Leydig cells in the control group was estimated to be 18.7 x 10(6) (coefficient of variation = 0.11), which is comparable to previous estimations. In the group exposed to bismuth the mean was 15.5 x 10(6) (coefficient of variation = 0.18). The observed 17% difference between the two groups was statistically significant (2P = 0.019). The inter-individual variation was largest in the bismuth-exposed group. Testis weight and body weight were not significantly reduced after bismuth exposure. These findings support the hypothesis that bismuth has a direct toxic effect on rat Leydig cells and underscores the potential risks of bismuth on male reproduction.


β-Arrestin1 regulates the morphology and dynamics of microglia in zebrafish in vivo.
Microglia are the primary immune cells in the central nervous system. Microglia typically exist in a 'resting' state in the healthy brain, with ramified processes dynamically exploring the surrounding microenvironment. They become 'activated' under pathological conditions with marked changes in morphology. However, the regulation of their morphology dynamics remains poorly understood. Here, using in vivo time-lapse imaging and three-dimensional morphology analysis of microglia in intact zebrafish larvae, we found that β-arrestin1, a multifunctional protein involved in various signal transductions, cell-autonomously regulated the microglial morphology. Knockdown of β-arrestin1 increased the volume size and process number of microglia but reduced the deformation speed in the resting state. Meanwhile, β-arrestin1 down-regulation led to a high frequency of phagocytic behaviour of microglia. These defects were partially rescued by over-expressing human β-arrestin1 in microglia. Our study indicated that microglial dynamics in the resting state can be regulated cell-autonomously by β-arrestin1 signalling.


Development and optimization of Lysis gene E as a counter-selection marker with high stringency.
Seamless modification of bacterial chromosomes is widely performed in both theoretical and practical research. For this purpose, excellent counter-selection marker genes with high stringency are needed. The lysis gene E was first constructed under the control of the PL promoter and the cI857 repressor. At 42°C, it could effectively kill Escherichia coli and seamless modification in this bacterium using E as a counter-selection marker was successfully conducted. It also works in another gram-negative strain, Serratia marcescens, under the control of the Arac/PBAD regulatory system. By combining lysis gene E and kil, the counter-selection frequencies of the PL -kil-sd-E cassette in E. coli reached 4.9 × 10-8 and 3.2 × 10-8 at two test loci, which are very close to frequencies observed with the best counter-selection systems reported, the inducible toxin systems. Under the control of the Arac/PBAD , the counter-selection frequency of PBAD -kil-sd-E in S. marcescens reached the level of 10-7 at four test loci. By expressing the araC gene from plasmid pKDsg-ack, 5- to 17-fold improvements in counter-selection stringency were observed at these loci. A surprisingly low counter-selection frequency of 4.9 × 10-9 was obtained at the marR-1 locus, which reflects the highest stringency for a counter-selection cassette reported thus far. Similarly, at the araB locus of E. coli, the counter-selection frequency of PBAD -kil-sd-E was 3 × 10-9 after introducing plasmid pKDsg-ack. We have developed and optimized a new universal counter-selection marker based on lysis gene E. The best counter-selection stringency of this new marker exceeds the inducible toxin system several fold. Our work can also provide inspiration for improving counter-selection stringency based on existing markers.


Common genetic determinants of halothane and isoflurane potencies in Caenorhabditis elegans.
Genetics provides a way to evaluate anesthetic action simultaneously at the molecular and behavioral levels. Results from strains that differ in anesthetic sensitivity have been mixed in their support of unitary theories of anesthesia. Here the authors use the previously demonstrated large variation of halothane sensitivities in Caenorhabditis elegans recombinant inbred strains to assess the similarities of the determinants of halothane action with those of another volatile anesthetic, isoflurane. The recombinant inbred strains, constructed from two evolutionarily distinct C. elegans lineages, were phenotyped. A coordination assay on agar quantified the sensitivity to the volatile anesthetics; median effective concentrations (EC50s) were calculated by nonlinear regression of concentration-response data and were correlated between the drugs for those strains tested in common. Genetic loci were identified by statistical association between EC50s and chromosomal markers. The recombinant inbred strains varied dramatically in sensitivity to halothane and isoflurane, with a 10-fold range in EC50s. Heritability estimates for each drug were imprecise but altogether high (49-80%). Halothane and isoflurane EC50s were significantly correlated (r=0.71, P < 10(-9)). Genetic loci controlling sensitivity were found for both volatile anesthetics; the most significant determinant colocalized on chromosome V. A smaller recombinant inbred strain study of ethanol-induced immobility segregated different genetic effects that did not correlate with sensitivity to either halothane or isoflurane. The genetic determinants driving the large variation in anesthetic sensitivity in these C. elegans recombinant inbred strains are very similar for halothane and isoflurane sensitivity.


Bladder and rectal complications following radiotherapy for cervix cancer.
One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.


Non-additivity of adrenaline and galanin effects on 86Rb efflux and membrane potential in mouse B-cells suggests sharing of common targets.
Adrenaline and galanin inhibit insulin release through strikingly similar mechanisms triggered by distinct receptors in pancreatic B cells. In this study we evaluated whether activation of alpha 2-adrenoceptors and galanin receptors use a common or only a similar transduction pathway. The membrane potential of B-cells was measured with intracellular microelectrodes and 86Rb efflux was monitored in normal mouse islets perifused with a medium containing 15 mM glucose. At a maximally effective concentration of 10 microM, adrenaline partially repolarized the membrane, inhibited but did not abolish electrical activity, and caused a decrease in 86Rb efflux (due to a lesser activation of Ca(2+)- and voltage-activated K+ channels). In the presence of 10 microM adrenaline, galanin had no effect on membrane potential, electrical activity and 86Rb efflux. Decreasing the concentration of glucose from 15 to 6 mM repolarized the B-cell membrane to the same extent as did adrenaline but did not prevent galanin from causing an additional hyperpolarization. In contrast to galanin, diazoxide, a selective opener of ATP-sensitive K+ channels still produced a small hyperpolarization and further decrease in 86Rb efflux when added at a low concentration (15 microM) to a medium containing 10 microM adrenaline. At a high concentration (250 microM), diazoxide repolarized the membrane to the resting potential and markedly accelerated 86Rb efflux both in the presence and absence of adrenaline. The non-additivity of the effects of adrenaline and galanin suggests that alpha 2-adrenoceptors and galanin receptors share common targets in pancreatic B-cells.


Insight into the synergetic, steric and energetic properties of zeolitization and cellulose fiber functionalization of diatomite during the adsorption of Cd(ii): advanced equilibrium studies.
The adsorption potentiality of zeolitized diatomite (ZD) frustules and their cellulose hybridized (C/ZD) product for Cd(ii) ions was assessed in synergetic studies to investigate the impact of the modification processes. The adsorption properties were illustrated based on the steric and energetic parameters of the applied advanced equilibrium modeling (monolayer model of one energy). The cellulose hybridization process increased the adsorption properties of Cd(ii) significantly to 229.4 mg g-1 as compared to ZD (180.8 mg g-1) and raw diatomite (DA) (127.8 mg g-1) during the saturation state. The steric investigation suggested a notable increase in the quantities of the active sites after the zeolitization (Nm = 62.37 mg g-1) and cellulose functionalization (Nm = 98.46 mg g-1), which illustrates enhancement in the Cd(ii) uptake capacity of C/ZD. Moreover, each active site of C/ZD can absorb about 4 ions of Cd(ii) ZD, which occur in a vertical orientation. The energetic studies, including Gaussian energy (<8 kJ mol-1) and retention energy (<8 kJ mol-1), demonstrate the physical uptake of Cd(ii), which might involve cooperating van der Waals forces (4-10 kJ mol-1), hydrophobic bonds (5 kJ mol-1), dipole forces (2-29 kJ mol-1), and hydrogen bonding (<30 kJ mol-1) in addition to zeolitic ion exchange mechanisms (0.6-25 kJ mol-1). The behaviors and values of entropy, internal energy, and free enthalpy as the assessed thermodynamic functions validate the exothermic and spontaneous properties of the Cd(ii) retention by ZD and the C/ZD composite.


Structural and orientational studies of chiral N-[4(1-pyrene)butyroyl]-phenylalanine in cast film.
Cast films of chiral material N-[4(1-pyrene)butyroyl]-l-phenylalanine (Py-l-Phe) and the racemic modification (the 1:1 mixture of Py-l-Phe and Py-d-Phe) have been investigated in the present study. The microscopic structure, molecular orientation and the aggregation in the film have been studied by using ultraviolet-visible (UV-vis) and infrared (IR) spectroscopy. When a cast film is formed from the chloroform solution at room temperature, the J-aggregates of Py-l-Phe and Py-d-Phe are observed by UV-vis spectra. A comparison of Fourier transform infrared (FT-IR) transmission and reflection-absorption (RA) spectroscopy has been applied to reveal the orientation and structural characterization of the cast films. It has been found that the pyrenyl ring in the cast film of Py-l-Phe assumes a nearly vertical orientation with respect to the surface of the solid substrate. And there are two different hydrogen bonding species, cyclic dimer and linear dimer, exist in carboxyl groups in cast films. The detailed analysis of the OH and NH stretching modes of Py-l-Phe and Py-d-Phe allows us to reveal the hydrogen bonds existing in the films.


Relating student perceptions of readiness to student success: A case study of a mathematics module.
This study correlates the readiness survey scores of bona fide first year university students with their success in a mathematically based first year module. It follows on the need for skilled individuals in the fields of Science and Technology that exists across the globe and is continually becoming the focus of educational institutions world-wide. Similarly, in South Africa, universities were instructed to increase their intake of students in the fields of Science and Technology so as to provide for the technology orientated needs of the country, as well as to increase participation of previously disadvantaged race groups in these fields. In response to this instruction, universities increased the number of students enrolled in Science and Technology fields by 23% in recent years. The challenge is now to ensure that these students exit the university with a suitable degree in the shortest possible time. Statistics published by the South African Council of Higher Education affirms the extent of this challenge faced by universities-only 51% of students enrolled in the fields of Science and Technology complete their 3-year undergraduate degrees, and some of them took as long as 6 years to complete the 3-year degrees. This still leaves 49% of students that either took more than 6 years to complete their degrees, or did not complete their degrees at all. The underlying cause(s) for these failures must be identified and addressed. As a starting point in this discussion, the questions that this study aim to answer are whether first year students are in fact as prepared for the challenges at university as they perceive themselves to be; and whether student readiness (or lack thereof) can be a root cause for the low throughput rates. This study determines how prepared first year students, at a leading South African university, perceive themselves to be for the demands of university and, specifically, how their perceptions of their readiness in different areas correlate with their academic success in a mathematically based module. The correlation is determined by analysing data gathered through a readiness survey that is completed by first year students at the beginning of the academic year, and their final mark in the mathematics based first year module. The survey is a standardised, self-evaluation tool originally developed by the University of Pretoria. It is also applied at the university where this study is conducted. The survey measures the preparedness of students in different areas and the empirical study shows that there is a statistically significant correlation between the perception of the students regarding their planning ability and the final mark obtained in the mathematics based module.


The Streptomyces coelicolor whiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation.
A non-sporulating mutant (whiB218) of Streptomyces coelicolor A3(2), which proved to contain a deletion of more than 5 kb of DNA including whiB, was complemented by a small cloned DNA fragment, deduced from DNA sequencing to encode a protein of only 87 amino acids. This protein would bear some similarities to transcription factors, including an acidic, somewhat amphipathic alpha-helical region predicted near its N-terminus, and a basic alpha-helical region predicted at its C-terminus. A point mutation (whiB70) giving a phenotype indistinguishable from that of the whiB218 deletion mutant would cause a leucine to proline change at the start of the latter region. The whiB homologue from the closely related species S. lividans differed at only one base from its S. coelicolor counterpart, and would specify an identical polypeptide.


Relationship between the Cycle Threshold Value (Ct) of a Salmonella spp. qPCR Performed on Feces and Clinical Signs and Outcome in Horses.
The objective of this retrospective study was to evaluate the clinical significance of fecal quantitative real-time polymerase chain reaction (qPCR) Salmonella results when taking the cycle threshold values (Ct) into account. The study included 120 Salmonella qPCR-positive fecal samples obtained from 88 hospitalized horses over a 2-year period. The mean Ct of the qPCR test was evaluated in regard to (1) clinical outcome and (2) systemic inflammatory response syndrome (SIRS) status (no SIRS, moderate SIRS, or severe SIRS) of the sampled horses. An ROC analysis was performed to establish the optimal cut-off Ct values associated with severe SIRS. The mean ± SD Ct value was significantly lower in samples (1) from horses with a fatal issue (27.87 ± 5.15 cycles) than in surviving horses (31.75 ± 3.60 cycles), and (2) from horses with severe SIRS (27.87 ± 2.78 cycles) than from horses with no (32.51 ± 3.59 cycles) or moderate (31.54 ± 3.02 cycles) SIRS. In the ROC analysis, the optimal cut-off value of Ct associated with a severe SIRS was 30.40 cycles, with an AUC value of 0.84 [95% confidence interval 0.76-0.91] and an OR of 0.64 [0.51-0.79]. Results suggest that including the Ct value in the interpretation of fecal qPCR results could improve the diagnostic value of this test for clinical salmonellosis in horses.


Tetracha hope 1838 of the Turks and Caicos Islands (coleoptera, carabidae, cicindelinae).
A new species, Tetracha (Neotetracha) naviauxi, and a new subspecies, Tetracha (Tetracha) sobrina caicosensis, are described from the Turks and Caicos Islands. The key to Tetracha species in Naviaux (2007) is adapted to accommodate Tetracha naviauxi. Tetracha sobrina caicosensis is compared to other Caribbean subspecies of Tetracha sobrina.


Cyclin D-dependent kinases, INK4 inhibitors and cancer.
The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. The components of this pathway are gene families with a high level of structural and functional redundancy and are expressed in an overlapping fashion in most tissues and cell types. Using classical transgenic technology as well as gene-targeting in ES cells, a series of mouse models have been developed to study the in vivo function of individual components of this pathway in both normal homeostasis and tumor development. These models have proven to be useful to define specific as well as redundant roles among members of these cell cycle regulatory gene families. This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. As a consequence, some of these molecules are currently being considered as targets for cancer therapy, and several novel molecules, such as Cdk inhibitors, are under development as potential anti-cancer drugs.


Editorial Commentary: Combined Anterior Cruciate Ligament Reconstruction and Medial Meniscal Transplantation Improve Functional Outcomes When Properly Indicated.
The anterior cruciate ligament (ACL) and medial meniscus both contribute to anteroposterior translation of the tibia. Biomechanical studies have found increased translation at both 30° and 90° when transecting the posterior horn of the medial meniscus, and clinically, medial meniscal deficiency has been shown to have a 46% increase in ACL graft strain at 90°. Medial meniscal deficiency is a risk factor for failure after ACL reconstruction, with a hazard ratio of 15.1. The combination of meniscal allograft transplantation and ACL reconstruction is technically demanding but results in mid- to long-term clinical improvement in well-indicated patients. Patients with medial meniscal deficiency and failed ACL reconstruction or with ACL deficiency and medial-sided knee pain due to meniscal deficiency are candidates for combined procedures. On the basis of our experience, acute meniscal injury is not an indication for primary meniscal transplantation in any setting. Surgeons should repair the meniscus if reparable or perform partial meniscectomy and see how the patient responds. There is insufficient evidence to show that early meniscal transplantation will be chondroprotective. We reserve this procedure for the indications previously described. Severe osteoarthritis (Kellgren-Lawrence grades III and IV) and Outerbridge grade IV focal chondral defects of the tibiofemoral compartment that are not amenable to cartilage repair are absolute contraindications to the combined procedure.


Augmentation of beneficial arthropods by strip-management : 1. Succession of predacious arthropods and long-term change in the ratio of phytophagous and predacious arthropods in a meadow.
A 5-year-field experiment was performed in a meadow to test the effect of strip-management (small unmown strips alternating with broad mown strips, Fig. 1) on the abundance and composition of arthropods. The species number and density of most predator groups increased from year to year. The succession (parallel to the development of the unmown strips) favoured more specialized species, so that the initial pioneer species become less abundant in consecutive years. In spiders, this succession leads from a dominance of Linyphiidae to a dominance of Lycosidae; the spider biomass increases and probably predator pressure by spiders is augmented. The stability of the predator community (measured as the variance of their frequency in successive years) is higher than that of the phytophagous groups. Under strip-managed conditions the abundance ("activity density") of most arthropod groups decreases by an average of ca. 12%. The trophic levels, however, are affected to different extents and strong species-specific preferences were found as well. These combined effects lead to constant increase in the ratio of predacious and parasitic to phytophagous insects in the strip-managed area and probably lead also to an increase of the predator pressure facing phytophagous insects. Strip-management is discussed as an important technique among integrated methods for the biological control of pests.


Ionic strength dependent enzyme activities of elastase.
Peptidase and esterase activities of elastase were each altered separately by the ionic strength of the buffer used. The esterase activity is exerted in a lower ionic strength medium where the peptidase activity is not detected.


Reconciling the actual and nominal exposure concentrations of microplastics in aqueous phase: Implications for risk assessment and deviation control.
The deviation between actual and nominal concentrations of microplastics (MPs), as a long-standing issue, has been critically commented. However, there is still a lack of quantitative assessment and reconciling practice on the deviation. In this study, a total of 210 deviations were recompiled to thoroughly examine this issue. It was shown that up to 81 (39%) deviations exceeded the recommended ± 20% variation specification, highlighting that the deviation of MPs should not be neglected. This study attempted to reconcile the deviation based on the most prominent driving factors. Specifically, the game theory-based SHapley Additive exPlanations (SHAP) algorithm identified that the particle size was the most important factor affecting the deviation. Subsequently, at each size magnitude, a significant linear correlation between the logarithmic actual and nominal concentrations was determined, which provided a sound basis for estimating the actual concentration from the nominal one. Furthermore, deviations of different size classes were simulated through 10, 000 points, suggesting that the ± 20% deviation variation could be well maintained within a specific concentration range. Moreover, the potential interaction effects between factors were quantified by SHAP interaction values, with more detailed conversion bases proposed. Additionally, several control measures were recommended to reduce the deviation of MPs.


Epiphyseal distraction and hybrid reconstruction using polymethyl methacrylate construct combined with free non-vascularized fibular graft in pediatric patients with osteosarcoma around knee: A case report.
In children with osteosarcoma around the knee joint without epiphysis involvement, joint-sparing surgery seems to be an ideal way to retain knee joint function. However, there are two points of debate with regard to the technique: How to accurately achieve a safe surgical margin, and how to achieve intercalary reconstruction of the massive bone defect following resection of the tumor. We present the case of an 8-year-old girl with osteosarcoma of the distal femur without involvement of the epiphysis. Epiphyseal distraction was applied to separate the epiphysis and metaphysis, and this provided a safe surgical margin. The massive bone defect was reconstructed with a custom-made antibiotic-loaded polymethyl methacrylate (PMMA) construct combined with a free non-vascularized fibular graft. Six months after surgery, bone union between the autograft and host bone was confirmed in both the proximal and distal femur by computer tomography (CT) examination. Moreover, considerable callus formation was found around the PMMA construct. After 28 mo of follow-up, there was no sign of recurrence or metastasis. The patient could walk without any aid and carry out her daily life activities satisfactorily. In cases of osteosarcoma without epiphysis involvement, epiphyseal distraction can be easily applied to obtain a safe margin. Hybrid reconstruction with an antibiotic-loaded PMMA construct combined with a free non-vascularized fibular graft has the advantages of being easy to manufacture, less time-consuming to place, and less likely to get infected, while also ensuring bone union. Our case provides an alternative technique for biological reconstruction after joint-sparing surgery in patients with osteosarcoma around the knee without epiphyseal involvement.


A case of infectious heterotopic ossification in the appendectomy scar, which formed an inflammatory granuloma.
Inflammatory granulomas often develop in surgical scars due to the presence of foreign bodies, such as sutures. These granulomas are called Schloffer's tumors. Here, we report a case of heterotopic ossification(HO) in an appendectomy scar that formed an inflammatory granuloma following HO infection. A 90-year-old woman was referred to our hospital with a chief complaint of a painful mass in the right lower quadrant of her abdomen. She had a history of acute appendicitis, for which she underwent an appendectomy approximately 70 years previously. Imaging studies demonstrated a tumor containing a linear-shaped agent located in the abdominal wall under the surgical scar where the appendectomy was performed. She was then diagnosed with Schloffer's tumor, for which she underwent surgical resection. However, histopathological examination revealed that the tumor was a fibrous connective tissue mass with a lamellar bone inside.


Degradation and intracellular phosphorylation of showdomycin.
The anti-tumor agent showdomycin is degraded in the presence of 0.05 M NH4HCO3 (pH 8.0) to a compound which carries a negatively charged group. Together with previous data (Darnall et al., 1967) it is suggested that ammonia causes a basic hydrolysis of the maleimide moiety under formation of a maleic acid-like compound. During this modification the C-glycosidic bond is not split. Intracellularly, in mouse lymphoma cells (L5178y), showdomycin is phosphorylated to showdomycintriphosphate, via the mono- and diphosphate stage.


Endovascular treatment of extracranial carotid artery stenosis: update on carotid angioplasty and stenting.
The endovascular treatment of carotid artery stenosis has undergone substantial refinement since its introduction, and carotid artery angioplasty and stenting is now widely performed on symptomatic and asymptomatic patients. Well-designed, large randomized prospective trials showed that carotid endarterectomy provided a significant and durable benefit to selected patients with significant carotid narrowing. Many trials are currently under way comparing endovascular stenting and surgery. Two recently published trials suggest endovascular stenting is at least as good as carotid endarterectomy in terms of safety and efficacy. In the future, carotid stenting may become the standard procedure for patients with significant carotid occlusive disease and a high estimated risk of future stroke.


Systemic lupus erythematosus - a state of hyperinterferonemia?
On the basis of immunologic and microbiologic data as well as recent observations it is postulated that interferon is responsible for many of the clinical signs and symptoms in systemic lupus erythematosus such as alopecia, joint manifestations, fever and leukopenia. Recognition of the important role of interferon in active systemic lupus erythematosus leads to some practical conclusions: a) a new therapeutic approach to active lupus must consider a treatment which will lead to reduced interferon activity; b) one of the laboratory parameters of activity of the disease may be interferon measurements.


Increased anaphylatoxins (C3a and C4a) in psoriatic sera.
We measured C3a and C4a anaphylatoxins in the serum of 56 psoriatic patients and 36 healthy control subjects by radioimmunoassay in order to clarify the mechanism of complement activation occurring in psoriatic lesions. Whereas a small amount of anaphylatoxins were demonstrable even in the sera of healthy adults, the serum concentrations of C3a and C4a anaphylatoxins were significantly higher in psoriatic patients than those in non-psoriatic controls. The increased serum anaphylatoxin levels did not correlate well with either the extent or the activity of the skin lesions, but a comparison of anaphylatoxin levels in 10 patients before and after successful treatment of skin lesions showed that the serum anaphylatoxin levels decreased with improvement of the skin lesions. Our results suggest that complement activation takes place in psoriatic patients chiefly via the classical pathway.


Race-Specific Impact of Conventional Surgical Risk Score on 1-Year Mortality After Transcatheter Aortic Valve Replacement.
Interracial differences in the distribution and prognostic value of conventional Society of Thoracic Surgeons (STS) score on long-term mortality after transcatheter aortic valve replacement (TAVR) are uncertain. This study aims to compare the impact of STS scores on clinical outcomes at 1-year after TAVR between Asian and non-Asian populations. We used the Trans-Pacific TAVR (TP-TAVR) registry, a multinational multicenter, observational registry involving patients undergoing TAVR at 2 major centers in the United States and 1 major center in Korea. Patients were classified into 3 groups (low, intermediate, and high-risk) according to the STS score and compared between STS risk groups and race. The primary outcome was all-cause mortality at 1-year. Among 1,412 patients, 581 were Asian and 831 were non-Asian. The distribution of the STS risk score group was different between Asian and non-Asian groups (62.5% low-, 29.8% intermediate-, and 7.7% high-risk in Asian vs 40.6% low-, 39.1% intermediate-, and 20.3% high-risk in non-Asian). In the Asian population, the all-cause mortality at 1-year was substantially higher in the high-risk STS group than in the low- and intermediate-risk groups (3.6% low-risk, 8.7% intermediate-risk, and 24.4% high-risk; log-rank P < 0.001), which was primarily driven by noncardiac mortality. In the non-Asian group, there was a proportional increase in all-cause mortality at 1-year according to the STS risk category (5.3% low-risk, 12.6% intermediate-risk, and 17.8% high-risk; log-rank P < 0.001). In this multiracial registry of patients with severe aortic stenosis who underwent TAVR, we identified a differential proportion and prognostic impact of STS score on 1-year mortality between Asian and non-Asian patients (TP-TAVR [Transpacific TAVR Registry]; NCT03826264).


Reversing the discovery paradigm: a new approach to the combinatorial discovery of fluorescent chemosensors.
We report here a new approach to the discovery of fluorescent chemosensors in which a new signaling mechanism allows a core fluorophore to be used in a combinatorial search for new binding events, thus reversing the reigning discovery paradigm.


Angiopoietin-1 aggravates atherosclerosis by inhibiting cholesterol efflux and promoting inflammatory response.
Angiopoietin-1 (Ang-1), a secreted protein, mainly regulates angiogenesis. Ang-1 has been shown to promote the development of atherosclerosis, whereas little is known about its effects on lipid metabolism and inflammation in this process. Ang-1 was transfected into ApoE-/- mice via lentiviral vector or incubated with THP-1 derived macrophages. Oil red O and HE staining were performed to measure the size of atherosclerotic plaques in ApoE-/- mice. Immunofluorescence was employed to show the expression of target proteins in aorta. [3H] labeled cholesterol was performed to examine the efficiency of cholesterol efflux and reverse cholesterol transport (RCT) both in vivo and vitro. Western blot and qPCR were used to quantify target proteins both in vivo and vitro. ELISA detected the levels of pro-inflammatory cytokines in mouse peritoneal macrophage. Our data showed that Ang-1 augmented atherosclerotic plaques formation and inhibited cholesterol efflux. The binding of Ang-1 to Tie2 resulted in downregulation of LXRα, ABCA1 and ABCG1 expression via inhibiting the translocation of TFE3 into nucleus. In addition, Ang-1 decreased serum HDL-C levels and reduced reverse cholesterol transport (RCT) in ApoE-/- mice. Furthermore, Ang-1 induced lipid accumulation followed by increasing TNF-α, IL-6, IL-1β,and MCP-1 produced by MPMs, as well as inducing M1 phenotype macrophage marker iNOS and CD86 expression in aorta of ApoE-/- mice. Ang-1 has an adverse effect on cholesterol efflux by decreasing the expression of ABCA1 and ABCG1 via Tie2/TFE3/LXRα pathway, thereby promoting inflammation and accelerating atherosclerosis progression.


Coloseminal vesicle fistula after low anterior resection: Report of a case and review of the literature.
A rectoseminal vesicle fistula after a low anterior resection for rectal cancer is a rare complication despite their anatomic proximity. From a Medline search from 1966 to date, a total of twenty-one previous cases of coloseminal vesicle fistula have been reported. From these cases, eleven were a complication of laparoscopic low anterior resection for rectal cancer. This report presents the case of a 63-year-old patient who was readmitted to the hospital on the fifteenth postoperative day after his surgical intervention for fever, abdominal pain, dysuria and pneumaturia. A sinography with water-soluble contrast revealed a tract between the rectum and the seminal vesicle. The condition was treated conservatively with antibiotics, urinary catheter and a transanastomotic Malecot probe for abscess drainage. The fistula had completely recovered on postoperative day 71 and the patient is still symptoms free, six months after the complication developed. This case reinforces the presumed link between anastomotic leakage and rectoseminal vesicle fistula in cases of low anterior resection while reviewing and summarizing similar previously reported cases on the course of the disease, diagnostic procedures and treatment options. Seminal vesicle are susceptible to fistula in oncological resection of rectum. Both CT scan with water-soluble contrast or sinography are effective diagnostic examinations. Depending on the characteristics of the fistula, conservative approach may be adequate and benefits much less morbidities than the surgical options.


Methods for detecting associations between phenotype and aggregations of rare variants.
Although genome-wide association studies have uncovered variants associated with more than 150 traits, the percentage of phenotypic variation explained by these associations remains small. This has led to the search for the dark matter that explains this missing genetic component of heritability. One potential explanation for dark matter is rare variants, and several statistics have been devised to detect associations resulting from aggregations of rare variants in relatively short regions of interest, such as candidate genes. In this paper we investigate the feasibility of extending this approach in an agnostic way, in which we consider all variants within a much broader region of interest, such as an entire chromosome or even the entire exome. Our method searches for subsets of variant sites using either Markov chain Monte Carlo or genetic algorithms. The analysis was performed with knowledge of the Genetic Analysis Workshop 17 answers.


Update of intraocular lens implantation in children.
Cataract is a common problem that affects the vision in children and a major cause of amblyopia in children. However, the management of childhood cataract is tenuous and requires special considerations especially with regard to intraocular lens (IOL) implantation. Age at which an IOL can be implanted is a controversial issue. Implanting an IOL in very young children carries the risk of severe postoperative inflammation and posterior capsule opacification that may need other surgeries and may affect the vision permanently. Accuracy of the calculated IOL power is affected by the short eyes and the steep keratometric values at this age. Furthermore, choosing an appropriate IOL power is not a straight forward decision as future growth of the eye affects the axial length and keratometry readings which may result in an unexpected refractive error as children age. The aim of this review is to cover these issues regarding IOL implantation in children; indications, timing of implantation, types of IOLs, site of implantation and the power calculations.


Burkitt Lymphoma Presenting as Acute Pancreatitis: Report of 3 Cases and Review of the Literature.
Acute pancreatitis is a rare presentation in Burkitt lymphoma (BL) and may lead to delayed medical or unnecessary surgical treatment. Three cases of BL presenting as acute pancreatitis in the authors' institutions were described. Similar cases reported in the medical literature were collected and described along with the authors' cases. There were 12 cases described in the medical literature and hence a total of 15 cases of BL presenting as acute pancreatitis. Fourteen cases were the first diagnosis, and the other presented at lymphoma relapse. Twelve cases occurred in children under 15 years. Twelve patients had extrapancreatic disease. Three children were treated with surgery before diagnosis. Two patients died. Six of the remaining had adequate follow-up and were surviving in remission 8 months to 16 years after diagnosis. Lymphoma should be included in the differential diagnosis of acute pancreatitis in children. Acute pancreatitis in combination with malignant infiltration on imaging is highly suggestive of BL, especially in the jaundiced child.


Mechanistic study of 1,1-dimethylhydrazine transformation over Pt/SiO2 catalyst.
Catalytic oxidation of 1,1-dimethylhydrazine (UDMH) with molecular oxygen over Pt/SiO2 was studied by in situ FTIR spectroscopy coupled with online MS monitoring of the gas phase. An unusual two-step oxidation process was detected in experiments with the pulse UDMH feeding: initial UDMH oxidation over a fresh platinum surface quickly terminates due to the blockage of active sites; a time-separated second oxidation step corresponds to combustion of the surface residue. This residue consists of C[triple bond, length as m-dash]N nitrile groups formed via decomposition of the products of non-oxidative UDMH conversion, such as dimethylamine. The two-step oxidation picture is observed over a broad range of reaction temperatures and oxygen to UDMH ratios.


PTP1B regulates leptin signal transduction in vivo.
Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. Compared to wild-type littermates, PTP1B(-/-) mice have decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin-induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B(-/-) mice. Our data indicate that PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target to treat leptin resistance in obesity.


Non-covalent interactions in molecular systems: thermodynamic evaluation of the hydrogen bond strength in aminoalcohols.
In molecules with two functional groups that form hydrogen bonds, the structure-property relationship can depend significantly on the strength of intra-molecular hydrogen bonding. This bonding can cause a substantial conformational change that is accompanied by a frequency shift in the infrared spectrum, which provides the basis for experimental studies. Despite its great importance in biological systems, the available literature data for the strength of this bonding are scarce and not in agreement. In this work, we present the results of four thermodynamic methods for the determination of the strength of intramolecular hydrogen bonds. Comprehensive thermochemical analysis of 1-amino-2-alcohols and 2-amino-1-alcohols was performed with Fourier-transform infrared spectroscopy, high-level G4 quantum-chemical calculations, the homomorph scheme with enthalpies of vaporization and a group contribution method. With the combination of these four thermodynamic methods, the strength of intramolecular hydrogen bonding in 1,2-aminoalcohols and 2,1-aminoalcohols was evaluated quantitatively. The results were correlated with NBO parameters to find an explanation for the different strengths of intramolecular hydrogen bonds in total charge transfer and second order stabilization energies.


Endothelial cell activation in muscle biopsy samples is related to clinical severity in human cerebral malaria.
To test the hypothesis of vascular sequestration of parasitized erythrocytes in Plasmodium falciparum malaria in vivo, a pathologic and immunohistochemical study was done of the microvasculature of skeletal muscle biopsy samples from P. falciparum malaria patients at different stages of severity. Parasitized red blood cells sequestered in the skeletal muscle vessels were observed in samples from necropsies but were never demonstrated in biopsy specimens. Vascular cell adhesion molecule-1 and E-selectin expression was consistent only in specimens from cerebral malaria patients. Samples from such patients had strong staining of the constitutive endothelial adhesion molecules tested. The staining intensity gradually decreased in samples from persons with milder forms of the disease. Four of 13 patients with severe malaria had aggregates of red blood cells, occasionally parasitized inside the muscle fibers. These data suggest that skeletal muscle biopsy could be a useful model for the study of the pathogenesis of malaria in vivo.


Angiolymphatic invasion exerts a strong impact on surgical outcomes for stage I lung adenocarcinoma, but not non-adenocarcinoma.
Angiolymphatic invasion (ALI), representing lymphatic invasion (Ly) and intratumoral vascular invasion (V), is considered to be a useful prognostic factor for pathological stage I non-small cell lung carcinoma (NSCLC). However, the types of tumor for which prognoses are most influenced by ALI positivity have not previously been discussed, nor has the question of whether these findings should influence postoperative therapeutic decision-making after complete resection. The present study investigated 195 cases of stage I NSCLC treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. ALI-positive (ALI(+)) results were found in 31.8% of tumors, and 5.1% exhibited both Ly(+) and V(+). Five-year recurrence-free survival was significantly lower in ALI(+) cases (50.6%) than in ALI(-) cases (85.9%; p<0.0001, log-rank test). In particular, 5-year recurrence-free survival rate was only 10.0% for Ly(+)V(+) cases. ALI(+) correlated with high age, male sex, tumor size (>2.0 cm), elevated preoperative serum carcinoembryonic antigen level (≥5.0 ng/mL), high maximum standard uptake value (SUVmax) on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) (≥5.0), pleural invasion, and histological classification of non-adenocarcinoma (ADC). According to histopathological subset analyses, ALI(+) was associated with shorter recurrence-free survival than ALI(-) only among ADC patients (p<0.0001, log-rank test), and not among non-ADC patients (p=0.7710). High preoperative serum CEA level, high SUVmax on FDG-PET, pleural invasion, Ly(+), and V(+) were significant risk factors for recurrence in univariate Cox survival analysis among stage I ADC patients. Importantly, Ly(+) and V(+) were identified as independent risk factors for recurrence by multivariate analysis. Histopathological detection of ALI as a risk factor for recurrence should be considered for inclusion in the staging criteria and as additional information for determining postoperative adjuvant treatment of stage I NSCLC, particularly among ADC patients, but not among non-ADC patients.


Epidemiology, clinical characteristics and severity of gradual onset injuries in recreational road cyclists: A cross-sectional study in 21,824 cyclists - SAFER XIII.
Prevalence, clinical characteristics and severity of gradual onset injuries (GOIs) in cyclists are poorly documented. We determine the prevalence, anatomical regions/sites affected and severity of GOIs among entrants in a community-based mass participation event. Cross-sectional study; SETTING: Cape Town Cycle Tour; PARTICIPANTS: Race entrants. Of 35,914 entrants, 27,349 completed pre-race medical questionnaires. We studied 21,824 consenting cyclists (60.8% of entrants). Crude lifetime prevalence, retrospective annual incidence, anatomical region/sites, specific GOI, tissue type and GOI severity is reported. The lifetime prevalence of GOIs was 2.8%, with an annual incidence of 2.5%. More common anatomical regions affected by GOIs were lower limb (43.4%), upper limb (19.8%), and lower back (11.5%). The knee (26.3%), shoulder (13%), and lower back (11.5%) regions were mostly affected. The most common GOI was anterior knee pain (14.2%). Of the GOIs, 55% were in soft tissue. 50% of cyclists reported symptom duration >12 months, and 37.3% of GOIs were severe enough to reduce/prevent cycling. 2.5% recreational cyclists report a GOI annually. >50% of GOIs affect the knee, lower back and shoulder. GOIs negatively affect cycling. Risk factors related to GOIs in cyclists need to be determined to develop and implement prevention programs.


Biomechanics of patellar tendon autograft for reconstruction of the anterior cruciate ligament in the goat: three-year study.
This study examined the biomechanics of anterior cruciate ligament-patellar tendon autografts for as long as 3 years after surgery. Twenty-seven adult female goats were tested; four served as controls and the others received an autograft to the right knee with each left knee serving as an additional control. The animals with grafts were tested at 0 week (n = 4), 6 weeks (n = 4), 12 weeks (n = 4), 24 weeks (n = 3), 1 year (n = 5), and 3 years (n = 3) after surgery. The anteroposterior laxity of the knee joint, load-relaxation, and structural and material properties of the graft were tested. The anteroposterior laxity was significantly greater than that of the controls for all groups except at 3 years. Load-relaxation was greater than that of the control anterior cruciate ligaments, but in the 1 and 3-year grafts load-relaxation was less than that of the patellar tendons with 5 minutes of sustained loading. Between 12 and 52 weeks, the stiffness and modulus of the grafts increased 3-fold, but the improvement was slow afterward. At 3 years, the strength and stiffness of the grafts were 44 and 49% those of the control ligaments, respectively; the modulus was 37 and 46% that of the control anterior cruciate ligaments and patellar tendons, respectively. The persistent inferior mechanical performance at 3 years suggests that anterior cruciate ligament grafts may never attain normal strength.


Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience.
We carried out a retrospective analysis of 27 patients with Adenosine Deaminase (ADA) deficiency diagnosed in a single center from 1997 to the 2013, for evaluating whether data regarding types of disease-inducing mutations, biochemical and immunological features as well as clinical outcomes of patients treated with enzyme replacement or transplantation, were comparable to those obtained in multicenter studies. The ADA deficiency diagnosis was performed with biochemical, immunological and molecular techniques. Ten patients treated with hematopoietic stem cell transplantation and three in treatment with enzyme replacement were followed up in our center. Twenty-four different mutations were identified and five were not previously reported. Identical mutations were found among patients from the same Romani ethnic group or from the same geographical region. A more rapid recovery was observed in enzyme replacement treated patients in comparison with those transplanted that, however, showed a continuous and long-lasting improvement both in terms of immune and metabolic recovery. The data obtained in our single center are comparable with those that have been reported in multicenter surveys.


Systemic arterial calcium burden in patients with chronic limb-threatening ischemia.
5-year mortality of chronic limb-threatening ischemia (CLTI) is 50-60% and coronary artery disease (CAD) is the main cause of death of CLTI patients, followed by stroke. The aim of this study is to quantify and qualify the calcium load in different arterial territories in patients with CLTI. Prospectively, 60 patients with CLTI were included and received a full-body CT scan. 6 patients were excluded. Different arterial territories (the peripheral lower extremity arteries, coronary arteries, extracranial and intracranial carotid arteries, thoracic and abdominal aorta) were analyzed. Analysis and interrelations of both quantitative and semi-quantitative CT measurements was performed. Mean age was 72 years (range 47-95; SD 11.4). Almost all CLTI patients had calcified arterial beds (femoropopliteal 100%, crural 98.1%, coronary 100%, carotid bifurcation 96.2%, internal carotid artery 98.1%, thoracic aorta 96.2%, abdominal aorta 92.3%). Nearly all arterial territories had severe calcifications. 57% had a very high coronary Agatston score (>1000), and 35% extremely high (>2000). Calcifications in the lower extremity were significantly correlated to CAC score, carotid artery bifurcation calcification score, and to a lesser extent correlated to annular calcifications in the aorta. Very high and extremely high total CAC scores were strongly correlated with severe lower extremity arterial calcifications and severe carotid and intracranial internal carotid artery, thoracic and abdominal aorta calcifications in patients with CLTI patients. In CLTI patients nearly all arterial territories are severely calcified, suggesting that systemic calcification plays an important role in the poor outcome of this disease.


Tool perception suppresses 10-12Hz μ rhythm of EEG over the somatosensory area.
The perception of tools vs. other objects has been shown to activate the premotor (BA6) and somatosensory cortex (BA3), which neurally represent object affordance related to tool manipulability (Proverbio et al., 2011). The earliest tool/non-tool discrimination is represented by increased anterior negativity (210-270ms) in response to tools. In this study, we analyzed μ desynchronization with wavelet analysis based on EEG recordings in response to 300 familiar objects vs. tools in 11 participants. The results showed an early 140-175ms μ desynchronization over centro-parietal sites at approximately 10-12Hz during tool perception. The surface scalp distribution of μ power is compatible with neural generators located in the somatosensory cortex, but no source analysis was performed. These results support the hypothesis that there is a temporal and functional relationship between the rapid and transient μ suppression over the centro/parietal area and the successive increase in time-locked post-synaptic potentials (ERPs) in regions processing tool motor affordance.


Burrow structure and foraging costs in the fossorial rodent, Thomomys bottae.
A model for calculating the energy cost of burrowing by fossorial rodents is presented and used to examine the energetics of foraging by burrowing. The pocket gopher Thomomys bottae (Rodentia: Geomyidae) digs burrows for access to food. Feeding tunnels of Thomomys are broken into segments by laterals to the surface that are used to dispose of excavated soil. Energy cost of burrowing depends on both soil type and on burrow structure, defined by the length of burrow segments, angle of ascent of laterals, depth of feeding tunnels, and burrow diameter. In a desert scrub habitat, Thomomys adjust burrow segment length to minimize cost of burrowing. Observed segment lengths (mean=1.33 m) closely approximate the minimum-cost segment length of 1.22 m. Minimizing energy expended per meter of tunnel constructed maximizes efficiency of foraging by burrowing in the desert scrub. Burrow diameter and cost of burrowing increase with body size, while benefits do not, so foraging by burrowing becomes less enconomical as body size increases. Maximum possible body size of fossorial mammals depends on habitat productivity and energy cost of burrowing in local soils.


Co-exposure of polycarbonate microplastics aggravated the toxic effects of imidacloprid on the liver and gut microbiota in mice.
The joint toxicity of microplastics (MPs) and pesticides may be different from MPs or pesticides individually, however, the information about the combined toxicity of MPs and pesticides is not well understood. Herein, we investigated the joint toxicity of polycarbonate (PC) MPs and imidacloprid (IMI) on mice. After orally exposure for 4 weeks, PC and/or IMI lowered the body weight gain of mice. Single exposure of IMI induced the tissue damage in liver by disturbing the redox homeostasis, and PC significantly aggravated the imbalance of redox homeostasis by facilitating the accumulation of IMI in liver. Additionally, compared to single exposure of PC or IMI, PC+IMI exposure caused more severe damage to the gut microstructure and microbial diversity. Several key metabolic pathways, especially the lipid metabolism, were significantly affected. Overall, these findings provide new insight into understanding the potential risk of co-exposure of microplastics and pesticides to animal and human health.


Silver staining of nucleic acids. Applications in virus research and in diagnostic virology.
The rapid and sensitive method of silver staining of nucleic acids in polyacrylamide gels is used to visualise double-stranded (ds) and single-stranded (ss) molecules of both DNA and RNA. The binding of silver ions to nucleic acids in gels is stoichiometric and independent of the GC content of ds DNA. Silver staining can be applied to problems in virus research and to the analysis of clinical virus isolates.


Intraoperative Chertsey Test, is it a Reliable Alternative to Computed Tomography Scan for Diagnosing Syndesmotic Injuries of the Ankle?
The present study aims to evaluate the diagnostic exactitude of the intraoperative Chertsey test in tibiofibular syndesmotic injuries in patients with malleolar fractures, in comparison with a computed tomography (CT) scan. In this study, patients with malleolar fractures operated between 2018 and 2020 were examined. Thirty-nine patients were enrolled in the study. A three-dimensional preoperative CT scan was obtained. The opposite unfractured ankle was also scanned and considered as the control group. The Chertsey test was performed during the operation to assess the syndesmosis injury. Then, patients were partitioned into two distinct groups, considering the condition of their ankle, namely the Chertsey positive (unstable syndesmosis) group and the Chertsey negative (stable syndesmosis) group. The outcomes of the present survey illustrated that the Chertsey test was positive in 16 patients (41.03%) and negative in 23 patients (59.07%). The median of all CT scan parameters (anterior tibiofibular distances (TFD), middle TFD, posterior TFD, and maximal TFD and volume) before surgery in the group of patients with a positive Chertsey test was significantly higher, measured against the unfractured control group (P < 0.001 for all parameters). Furthermore, a comparison of CT scan parameters and syndesmosis space volume before surgery between the two groups of patients with positive and negative Chertsey test results showed that the measurement of parameters in Chertsey-positive patients was significantly higher than the Chertsey-negative patients (P < 0.001). Chertsey test could be used to diagnose syndesmosis injuries in patients with malleolar fractures due to its high importance in the outcome of patients.


Increased prevalence of non-communicable physical health conditions among autistic adults.
Previous research indicates autistic individuals die at a younger age than others and that this is possibly due in part to chronic physical health conditions. The present study used an anonymous, online survey to determine how common certain physical health conditions are among autistic adults, compared with non-autistic adults. We found autistic adults are more likely to develop heart conditions, lung conditions, and diabetes than non-autistic adults. Autistic females may be at higher risk of developing certain conditions (including respiratory conditions, asthma, and prediabetes) than autistic males. Finally, autistic individuals have increased health risks even when considering lifestyle factors (such as smoking, alcohol, and body mass index). This is still a relatively small study, and future research needs to confirm these findings and identify why these risks exist.


Tissue-specific accumulation, bioaccumulation, and depuration of liquid crystal monomers (LCMs) in adult zebrafish (Danio rerio).
This study investigated the properties of bioaccumulation, tissue-specific accumulation, and depuration of liquid crystal monomers (LCMs) in adult zebrafish (Danio rerio) exposed to a mixture of 39 LCMs for 19 days followed by depuration for 12 days. Tissue-specific accumulation of LCMs was examined at the time point of day 19, and we observed that the distribution of LCMs varied among different tissues with the following order of Σ39LCM concentrations, the intestine > brain > gill > liver > muscle. We also observed that the bioaccumulation potential of LCMs varied among LCM groups with different functional groups, and LCMs with the cyan group were prone to accumulate in zebrafish. Among the 39 target LCMs, nine exhibited bioconcentration factors (BCFs) >1000, indicating their great bioaccumulation potential in aquatic environments. The experimental BCFs of 22 LCMs in the present study were lower than the theoretical values predicted by the Estimation Programs Interface (EPI) Suite software developed by U.S. Environmental Protection Agency (USEPA), suggesting that their bioaccumulation potential might be overestimated by theoretical estimation techniques. Another interesting finding was the significant positive correlation relationship in both sexes of zebrafish (p < 0.01, r2 = 0.66 for male; p < 0.01, r2 = 0.41 for female) between logBCFww and logKow values of LCMs. Overall, this study provides fundamental information regarding the bioaccumulation potentials of LCMs, which could be helpful for further investigating the health risks of LCMs in aquatic environments.


To assess the occurrence of middle mesial canal using cone-beam computed tomography and dental operating microscope: An in vitro study.
Failures of root canal treatments are mainly attributed to missed canals and ignorance about the complex anatomy of the root canal system. One such example of anatomic variation is the middle mesial canal (MMC) in mandibular molars which is often missed, and literature on methods for identifying them is limited. This in vitro study aimed to assess the occurrence of MMCs with cone-beam computed tomography (CBCT) and then under magnification in the mandibular first and second molars. A total of 120 extracted intact human permanent mandibular first and second molars were selected. These were subjected to CBCT imaging and magnification for the detection of MMCs. The percentage of incidence in the detection of MMC was compared between these two methods. The incidence of MMC detected in mandibular molars using CBCT was 13.33% (16 of 120 teeth), while using a dental operating microscope, the incidence was 18.33% (22 of 120 teeth) and the comparison between the two methods was statistically not significant. The MMCs were classified based on the Pomeranz Classification. The most prevalent canal configuration was a confluent type which was found to be in 72% cases (16 of 22), followed by fin type which was 22.7% (5 of 22) and independent type was only 4.54% (1 of 22). The incidence of the location of MMC orifice was studied. In 50% of the cases, orifice was located closer to the mesiolingual canal, whereas in 27% of the cases, it was closer to the mesiobuccal canal and in 4.95% of the cases, it was detected midway. Since the incidence of MMC was higher with the use of a microscope, it is preferred to use simpler, chairside aids like magnification and ultrasonic troughing. On the other hand, one should be judicious while subjecting a case to preoperative CBCT evaluation owing to its ionizing radiation.


Gut-specific telomerase expression counteracts systemic aging in telomerase-deficient zebrafish.
Telomere shortening is a hallmark of aging and is counteracted by telomerase. As in humans, the zebrafish gut is one of the organs with the fastest rate of telomere decline, triggering early tissue dysfunction during normal zebrafish aging and in prematurely aged telomerase mutants. However, whether telomere-dependent aging of an individual organ, the gut, causes systemic aging is unknown. Here we show that tissue-specific telomerase expression in the gut can prevent telomere shortening and rescues premature aging of tert-/-. Induction of telomerase rescues gut senescence and low cell proliferation, while restoring tissue integrity, inflammation and age-dependent microbiota dysbiosis. Averting gut aging causes systemic beneficial impacts, rescuing aging of distant organs such as reproductive and hematopoietic systems. Conclusively, we show that gut-specific telomerase expression extends the lifespan of tert-/- by 40%, while ameliorating natural aging. Our work demonstrates that gut-specific rescue of telomerase expression leading to telomere elongation is sufficient to systemically counteract aging in zebrafish.


The prevalence of pediatric metabolic syndrome-a critical look on the discrepancies between definitions and its clinical importance.
The Metabolic Syndrome (MetS) describes the clustering of cardio-metabolic risk factors-including abdominal obesity, insulin resistance, elevated blood pressure, high levels of triglycerides, and low levels of high-density lipoproteins-that increase the risk for developing cardiovascular diseases and type 2 diabetes mellitus. However, a generally accepted definition of MetS in pediatric patients is still lacking. The aim was to summarize current prevalence data of childhood MetS as well as to discuss the continuing disagreement between different pediatric definitions and the clinical importance of such diagnosis. A systematic literature search on the prevalence of pediatric MetS was conducted. Articles that were published during the past 5 years (2014-2019), using at least one of four predetermined classifications (International Diabetes Federation, Cook et al., Ford et al., and de Ferranti et al.), were included. The search resulted in 1167 articles, of which 31 publications met all inclusion criteria. The prevalence of MetS ranged between 0.3 and 26.4%, whereby the rising number of children and adolescents with MetS partly depended on the definition used. The IDF definition generally provided the lowest prevalences (0.3-9.5%), whereas the classification of de Ferranti et al. yielded the highest (4.0-26.4%). In order to develop a more valid definition, further research on long-term consequences of childhood risk factors such as abdominal obesity, insulin resistance, hypertension, and dyslipidemia is needed. There is also a temptation to suggest one valid, globally accepted definition of metabolic syndrome for pediatric populations but we believe that it is more appropriate to suggest definitions of MetS that are specific to males vs. females, as well as being specific to race/ethnicity or geographic region. Finally, while this notion of definitions of MetS specific to certain subgroups is important, it still needs to be tested in future research.


Magnetic resonance images of neuro-Behçet syndrome show precise brain stem lesions. Report of a case.
Neuro-Behçet syndrome was investigated with magnetic resonance imaging (MRI) showing precise images of brain stem lesions, and therefore suggesting the clinical usefulness of MRI in diagnosis of neuro-Behçet syndrome.


A Novel Method for the Delivery of Antimetabolites During Glaucoma Surgery.
Current techniques for the delivery of antimetabolites, such as mitomycin C, tend to be very variable among surgeons and risk uncontrolled contact with the conjunctivae, which may result in delayed wound healing, wound dehiscence, and wound leakage postoperatively. We describe a novel technique which appear to allow a more precise and reproducible delivery of antimetabolite to the target area with minimal contact with the conjunctival edge. The technique involves the injection of an antimetabolite-soaked wick into the subconjunctival space posterior to the scleral flap using an intraocular lens injector system.


Is value-based healthcare a strategy to achieve universal health coverage that includes oral health? An Australian case study.
The 2021 Resolution on Oral Health by the 74th World Health Assembly supports an important health policy direction: inclusion of oral health in universal health coverage. Many healthcare systems worldwide have not yet addressed oral diseases effectively. The adoption of value-based healthcare (VBHC) reorients health services towards outcomes. Evidence indicates that VBHC initiatives are improving health outcomes, client experiences of healthcare, and reducing costs to healthcare systems. No comprehensive VBHC approach has been applied to the oral health context. Dental Health Services Victoria (DHSV), an Australian state government entity, commenced a VBHC agenda in 2016 and is continuing its efforts in oral healthcare reform. This paper explores a VBHC case study showing promise for achieving universal health coverage that includes oral health. DHSV applied the VBHC due to its flexibility in scope, consideration of a health workforce with a mix of skills, and alternative funding models other than fee-for-service.


Radiation dose and diagnostic accuracy of high-pitch dual-source coronary angiography in the evaluation of coronary artery stenoses.
"Flash Spiral" imaging is a new prospective ECG-triggered spiral scan mode that uses a very high-pitch for coronary computed tomography angiography (CTA). This enables complete image acquisition within one cardiac cycle with a very low radiation exposure. The aim of this study was to investigate the diagnostic accuracy, image quality, and effective radiation dose of prospectively ECG-triggered high-pitch spiral method (Flash spiral mode) of coronary CTA using dual-source technology for the evaluation of coronary artery stenoses. The study included 186 consecutive patients (115men, 71women; mean age: 53.37 years) who underwent coronary CTA. Coronary CTA was performed with a 128×2-slice dual-source CT (Somatom Definition Flash, Siemens, Germany) using a prospectively ECG-triggered high-pitch spiral mode. Patients were divided into three groups according to heart rate (≤65bpm, 66-75bpm, ≥76bpm) and body mass index (BMI) (20-24kg/m(2), 25-29kg/m(2), 30-34kg/m(2)) values. The correlation between heart rates, image quality and BMI values are investigated. A four-point scale (1=excellent, 4=poor/non-diagnostic) was used to rank the comparative image quality. Effective radiation doses were calculated. Also the correlation between radiation dose, sex and BMI values were investigated. In addition, diagnostic accuracy of CTA for detection of significant (≥50%) coronary artery stenoses was compared with invasive coronary angiography findings of 612vessel segments in 38patients. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rate were calculated. A total of 2976coronary artery segments were present. Of all coronary artery segments, 2381 (80%) had an image quality score of 1, and 1.5% segments were rated as "poor/non-diagnostic". When the correlation between heart rate and image quality is investigated, there was a significant difference between ≤65bpm and ≥76bpm groups. However, there was no significant difference between ≤65bpm and 66-75bpm groups. The mean effective dose was found as 1.3mSv (min: 0.5, max: 2.4mSv). The correlation between effective radiation dose and BMI was moderate. However, the correlation between gender and radiation dose was significant. Sensitivity, specificity, negative predictive value and accuracy of coronary CTA on a per-vessel segment were 90.1%, 97.4%, 98.6%, and 96.5%, respectively. Prospectively ECG-triggered high-pitch spiral mode coronary CTA provides high image quality and diagnostic accuracy, with very low radiation dose for evaluation and exclusion of coronary artery stenoses.


[Medial femoral neck fractures: possible reasons for delayed surgery. Part 2: Results of data from external inpatient quality assurance within the framework of secondary data evaluation].
In Germany a disproportionate number of patients with a femoral neck fracture still experience a delay in surgery. In 2008 delays of more than 48 h after admission occurred for 15.4 % of patients. This leads to increases in surgical and general complications as well as pressure sores. Possible reasons that lead to delayed operations were investigated in a nationwide study. Using nationwide data from the German inpatient external quality assurance program from the year 2008 the reasons for performing operations later than 48 h after hospital admission were examined both exploratory and analytically using a multiple logistic regression model considering combined effects. Surgery was more frequently delayed for patients who were admitted to hospital on Friday or Saturday, patients with a higher American Society of Anesthesiologists (ASA) classification, men, patients with malignant diseases, in the presence of infectious diseases and patients with heart disease. Operations carried out within the first 48 h were more frequent with displaced fractures and in the presence of hypertension or mental illness. The volume per hospital had no consistent effect on the time delay of surgery. During the week no significant differences between the departments were detected. On Friday or Saturday surgery was delayed more often when patients were admitted to a department of general surgery than to a department of trauma surgery or orthopedics. There are medical and non-medical reasons for delayed surgery of femoral neck fractures. Studies have confirmed that delayed surgery for femoral neck fracture harms the patients. Organizational reasons which prevent an immediate operation, e.g. admission on Friday or Saturday, should therefore be eliminated by improvements in hospital organization and staffing. These can be measures of individual hospitals or of several hospitals in cooperation. The target should be to ensure a comprehensive and timely provision of the highest quality care even at the weekend.


Overwintering of non-migrating strongyles in donkeys in the highveld of Zimbabwe.
Three two-year-old male donkeys from a communal area in the highveld of Zimbabwe were necropsied in July, the middle of the dry season. The strongylid populations of the three animals were very similar. Approximately 80 per cent of these populations consisted of adult worms and only just over 10 per cent were early third stage larvae. The most common species were Cylicostephanus minutus, Cyathostomum montgomeryi, Cylicocyclus nassatus and Cylicocyclus auriculatus. Nine other species of non-migratory strongyles were present in low numbers in one or more of the donkeys. These results indicate that survival of non-migratory strongyles of donkeys throughout the dry season in the highveld of Zimbabwe primarily occurs in the adult stage and not as inhibited early third stage larvae.


Pharmacologic characterization of beta blockers with special reference to the significance of nonspecific membrane effects.
Along with the beneficial effects of beta blockers in the ischemic derangements of myocardial energy metabolism are nonspecific membrane effects, which are thought to derive from the physicochemical interaction of the drugs with the cell membrane. These interactions are observed in various forms (e.g., membrane stabilizing action, quinidine-like action, cardiodepressant action), depending on the intensity of the interaction and on the method used for their detection. There may be still other manifestations that have not been detected so far, owing to our ignorance of their existence and our lack of an adequate method for their detection. The importance of the presence of specific chemical moieties in certain beta blockers with ability to trap peroxy radicals is also discussed.


Hyalinizing Clear Cell Carcinoma: Base of Tongue.
Hyalinizing clear cell carcinoma (HCCC) is a low grade, rare neoplasm originating from the minor salivary glands. It usually follows an indolent course and the main treatment modality is surgery. The prognosis of these tumours are good, hence it needs to be differentiated from other carcinomas with clear cells. Here we report a pathologically proven HCCC of the base of tongue.


Changes in the relationship between ambient fine particle concentrations and childhood lung function over 5 years.
Exposure to ambient fine particles, particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5), is a public health concern. Concentrations of ambient PM2.5 have changed temporally in the past 10 years after a series of action policies for improving air quality were implemented in Taiwan. In this study, temporal changes in the relationship between PM2.5 and lung function among children were investigated. A nationwide respiratory health survey was conducted among Taiwanese elementary and middle school students in 2011 and again in 2016-2017. A questionnaire was administered to students, for whom forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured using spirometry. During the study period, monthly concentrations of ambient PM2.5 were obtained from the monitoring stations of the Environmental Protection Administration. Lung function measurements were compared with ambient PM2.5 exposure using mixed-effects models. In the 2011 survey (mean PM2.5: 40.6 μg/m3), exposure to PM2.5 in the preceding 1-2 months was associated with a 2.2% decrease (95% confidence interval [CI]: -4.1%, -0.3%) in FVC and a 2.3% decrease (95% CI: -4.0%, -0.5%) in FEV1. By contrast, a significant relationship between PM2.5 concentrations and lung function was not observed in the 2016-2017 survey (mean PM2.5: 30.0 μg/m3). As improvement in air quality over time, the negative relationship between PM2.5 and childhood lung function tend to be not significant.


Susceptibility and immune responses after challenge with Flavobacterium columnare and Pseudomonas fluorescens in conventional and specific pathogen-free rare minnow (Gobiocypris rarus).
The susceptibility of fish from different culture environments to bacterial infection is not well known. The susceptibility and pathological changes of conventional (CV) and specific pathogen-free (SPF) rare minnow (Gobiocypris rarus) infected with two gram-negative bacteria, Flavobacterium columnare and Pseudomonas fluorescens are investigated. Rare minnows were intraperitoneally challenged with two bacterial species to first determine semi-lethal doses (LD50), and then with the LD50 dose, determine innate immune response. Infected rare minnows developed characteristic red bellies and then died. LD50 doses of F. columnare and P. fluorescens were 4.586 × 108 cfu/mL and 2.319 × 1010 cfu/mL for CV rare minnow, and 2.575 × 108 cfu/mL and 1.935 × 1010 cfu/mL, respectively, for SPF rare minnow. The results of RT-PCR showed that the highest levels of toll-like receptor 3 (TLR3), interleukin-6 (IL-6), interferon-2 (IFN-2) and rare minnow Z-DNA binding protein kinase (GrPKZ) mRNA were noticed at 6-48 h post-infection (hpi). In addition, TLR3, IL-6 and IFN-2 in F. columnare challenged rare minnow were more highly expressed than those in P. fluorescens challenged rare minnow, whereas as opposed in the expression of GrPKZ mRNA. Stimulation of innate immune responses is closely related to bacterial virulence. SPF rare minnow might be more susceptible to these bacteria than CV rare minnow, possibly due to their clean environment and lack of resistance. We speculate that clean environment renders rare minnow more susceptible to bacterial infections.


A monoclonal antibody directed against an organ-specific liver cell membrane antigen in rabbits.
We generated monoclonal antibodies after immunization of mice with rabbit liver-specific protein (LSP) preparations. One of these antibodies (2D3) showed an organ-specific and species-specific binding pattern as determined by immunohistological and ELISA techniques. Immunoelectron microscopy studies demonstrated that this antibody is bound exclusively to the liver cell membrane except in the region of the bile canaliculi. We further describe a simple ELISA technique for the detection of anti-LSP antibodies. Our study clearly demonstrates the presence of at least 1 organ-specific liver cell membrane antigen in rabbit LSP and shows antigenic differences between areas of the plasma membrane of hepatocytes.


The Fear of Pain Questionnaire-III: further reliability and validity with nonclinical samples.
The Fear of Pain Questionnaire-III (FPQ-III) is a 30-item self-report measure designed recently to assess fears about pain across three pain dimensions: severe, minor, and medical. We conducted three studies to replicate the factor structure of the FPQ-III and examine several psychometric properties of reliability and validity in nonclinical samples. A principal-axis with oblique rotation analysis provided strong empirical support for the three-factor solution of the FPQ-III (Study 1). In Study 2, results of the confirmatory factor analyses (CFA) confirmed the fit of the three-factor oblique model to an independent sample of data. In addition, we evaluated several measurement models to address issues related to convergent and discriminant validity for the FPQ-III. In Study 3, data from adult samples were analyzed for the adequacy of internal consistency and criterion-related validity of the FPQ-III. The FPQ-III total and scales showed high levels of reliability estimates across the three studies. Limitations and future research with the FPQ-III are discussed.


Efficacy of dose-adjusted EPOCH plus rituximab/R-CHOP regimens and the prognosis analysis in patients with MYC, BCL2/BCL6 gene copy number gain lymphoma and double-hit lymphoma: results from a single institution retrospective clinical study.
To compare the efficacy of rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) with traditional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimens in double-hit lymphoma (DHL) and gene copy number gain (CNG) lymphoma and to contrast the prognosis of these two disease types. We retrospectively examined 127 cases of newly diagnosed diffuse large B-cell lymphoma (DLBCL), and used fluorescence in situ hybridization (FISH) to detect genetic abnormalities in MYC, BCL2, and BCL6. In the two schemes, the 2-year progression-free survival (PFS) was higher for R-DA-EPOCH group than for R-CHOP (79.8% vs 57.5%, P=0.002), this advantage was also reflected in 2-year overall survival (OS) (81.6% vs 58.5%, P=0.002). In double CNG patients, R-DA-EPOCH regimen was significantly better than R-CHOP (P=0.007 for PFS, P=0.010 for OS), and R-DA-EPOCH has the same advantage in DHL patients (P=0.001 for PFS, P=0.047 for OS). For the two disease types, the PFS for DHL was inferior to that for double CNG (52.9% vs 72.4%, P=0.008), while the OS was not significantly different (P=0.050). Subgroup analysis showed that the PFS for double CNG with MYC and BCL2 was superior to that for DHL with MYC and BCL2 (P=0.043), this trend is also seen in double CNG and DHL with MYC and BCL6 (P=0.036). However, the OS was not significantly different between the two subgroups. Multivariate analyses showed that in DLBCL patients with genetic abnormality detected by FISH, the treatment and disease types were independent prognostic factors. The adverse reaction rates were similar in R-DA-EPOCH and R-CHOP (P>0.05). Our retrospective study shows that DHL has a poorer prognosis than double CNG. Based on its improved lifetime and good tolerance, R-DA-EPOCH is a promising regimen for DHL or double CNG, which is expected to become the first-line treatment for high-risk DLBCL types based on more clinical research.


Eu2+ as the structural probe in the phase transformation of CMSA by site-selective occupancy and adjustable multimode white luminescence in Ca2(Mg0.5Al0.5)(Si1.5Al0.5O7) akermanite based on high-aluminum blast furnace slag.
A tunable multimode white emission Ca2(Mg0.5Al0.5)(Si1.5Al0.5O7):Eu2+/Eu3+ phosphor was prepared by doping Eu2O3 in molten high-aluminum blast furnace slag. The structural probe Eu2+ was studied during phase transformation between the glassy state and Ca2(Mg0.5Al0.5)(Si1.5Al0.5O7) crystals based on site-selective Eu2+ occupancy. When the doped Eu2+ ions occupied two different Ca2+ sites in the matrix, blue light (421 nm) and green light (516 nm) emissions were observed corresponding to two types of Eu2+Ca2+, namely Eu2+Ca2+ (Mg2+ → Al3+) and Eu2+Ca2+ (Si4+ → Al3+). The effects of Eu concentration (0.1-2.0 mol%), heat treatment temperature (800-1000 °C), and thermal quenching temperature (30-150 °C) on the structural evolution of the emission unit were studied by differential scanning calorimetry (DSC), photoluminescence spectroscopy (PL) and X-ray diffraction (XRD) analyses. The Eu2+Ca2+ (Mg2+ → Al3+) structure formed by site-selective Eu2+ occupancy possessed better structural stability in the Ca2(Mg0.5Al0.5)(Si1.5Al0.5O7) crystal matrix, in favour of light-emitting diode (LED) illumination and plasma display panels (PDPs).


Immunologic release of histamine from dog lung: comparison of in vivo and in vitro responses in the same animal.
The purpose of this study was to compare, for the first time, antigen-induced histamine release from the lung in the same natively allergic dogs both in vitro and in vivo. In six dogs, maximal antigen-induced histamine release from the lung correlated closely in vitro and in vivo (r = 0.94), although it varied widely between dogs (0% to 75.5% of total tissue histamine content); similarly, the antigen concentration to produce 50% of maximal histamine release varied sixfold between dogs (40 micrograms/ml to 250 micrograms/ml). In each of five other dogs, terbutaline sulfate administered intravenously caused a dose-dependent inhibition of antigen-induced histamine release from lung fragments in vitro: the maximal inhibition produced by 1 mg/kg was 60 +/- 4.5% (mean +/- SEM). In these same dogs, 10(-5)M terbutaline incubated with lung fragments in vitro caused inhibition of antigen-induced histamine release comparable to 1 mg/kg terbutaline in vivo. Increasing the dose of terbutaline in vitro produced maximal inhibition at 10(-4)M with no greater effect of the drug at 10(-3)M (71.4 +/- 3.8% inhibition). In both experimental situations propranolol caused a dose-dependent inhibition of beta-adrenergic modulation of Ascaris-induced release of histamine. This result supports the conclusion that terbutaline produced its effects by actions mediated by beta-adrenergic receptors on pulmonary mast cells. This experimental approach provides a suitable preparation in which to estimate the effective dose of agonists that modulate antigen-induced mast cell function in vivo.


Global research trends on maternal separation paradigms as an early life stress model: A bibliometric analysis.
Maternal separation (MS) is an early life stress model that is often studied to determine how early life stress affects brain development and psychopathological adaptation. As society has developed, public health problems have become increasingly prominent, and this research area has attracted significant attention. However, to date, there has been no systematic bibliometric study on MS. The aim of this study was to analyze the trends and frontiers in MS using bibliometrics and provide a scientific reference to researchers in the field. Utilizing VOSviewer, CiteSpace, and Microsoft Excel, examined data obtained from the WoSCC, which encompasses the years 2002-2021. In this bibliometric study, we analyzed 6209 articles related to MS authored by 24,174 researchers across 121 countries and regions and published in 2219 journals. The United States had the most publications (2,232, 35.95%) and both the United States and the United Kingdom had the highest h-index. Institutions in the United States and France had the most published articles and citations. Keyword clustering analysis revealed associations between MS and adverse early life experiences, the hypothalamic-pituitary-adrenal (HPA) axis, stress, gene expression, and depression. This bibliometric analysis highlights the current research focus on the long-term effects of MS on emotional cognition, the HPA axis, epigenetic changes, and their links to gut microbiome imbalances. Future research may expand on these findings to investigate the underlying mechanisms and broader health and societal implications of MS. These results provide a comprehensive overview of the current research landscape in MS and offer valuable insights for researchers to guide future investigations in this field.


Associations of serum cortisol levels, stress perception, and stressful events with suicidal behaviors in patients with depressive disorders.
Stress is a well-known risk factor of suicide. However, there is a lack of research on the best psychobiological markers of stress for monitoring and predicting suicidal behaviors in depressed patients. We aimed to investigate the individual and interactive effects of serum cortisol levels and stress-related parameters, including perceived stress and life stressors, on suicidal behavior in depressed patients. At baseline, serum cortisol levels were measured and stress-related data, i.e., Perceived Stress Scale (PSS) scores and the number of stressful life events (SLEs), were collected from 1,094 patients with a depressive disorder, of whom 884 were followed up for 1 year. Suicidal behaviors evaluated at baseline included previous suicide attempts and baseline suicidal severity, while those at the 1-year follow-up were increased suicidal severity and fatal/non-fatal suicide attempts. Individual and interactive associations of exposure variables with suicidal outcomes were analyzed using logistic regression models after adjusting for relevant covariates. Higher serum cortisol levels were significantly associated with suicidal outcomes at the 1-year follow-up. In addition, higher PSS scores were significantly associated with higher baseline severity, whereas the number of SLEs was not associated with any suicidal outcomes. A significant interactive effect of cortisol level and PSS score on suicidal outcomes at the 1-year follow-up was observed. Higher cortisol levels and PSS scores were associated with increased suicidal severity and more fatal/non-fatal suicide attempts. The combination of serum cortisol levels and PSS scores may be useful for monitoring and predicting suicidal behaviors in depressed patients.