Accurate quantification of the influence of benthic macro- and meio-fauna on the geometric properties of estuarine muds by micro computer tomography

This paper describes the novel application of high resolution micro computer tomography (microCT) to the quantification of the properties of marine biogenic structures. CT scanning has been used to examine sediments in the past but the resolution of most previous techniques has been dependent upon commercial medical CT scanners which only have a slice thickness of ≥ 0.625 mm. In addition adequate software has not previously been available to rapidly quantify all the properties of biogenic structures. The microCT technique developed here used a standard core sample of estuarine sediment and new software was developed to calculate the axial variation of the following burrow parameters: number, diameter, volume, surface area and density. The increased resolution has resulted in the first quantification of meiofaunal burrow structures.A test core has shown, as an example, that the total volume of burrows created by macrofaunal organisms decreased from 827 mm³, within the top 15 mm of the core, to 204.2 mm³ at a depth 60 -75 mm within the core. Total burrow surface area decreased from 1883 mm² to 512 mm², for these depth ranges, respectively and burrow diameter ranged from 2.37-2.58 mm, remaining fairly constant between depths. Meiofaunal burrow structures decreased from 1.3-0.1 mm³ within the top 6 mm of the core with burrow surface area decreasing from 33.52-3.4 mm². Again, burrow diameter remained relatively constant, ranging from 0.23-0.25 mm.Quantification to this resolution is required to identify the impact of infaunal organisms on factors such as oxygen penetration, vertical and horizontal (across burrow walls) gradients in redox conditions and chemical/nutrient speciation and flux. The quantification of these burrow properties will improve the ability to examine the interrelationships between chemical, physical and biological processes and their role in ecological functioning. The present study indicates that there is potential for further development of this software to allow more detailed analysis of burrow structures and surface features including parameters such as burrow length, shape and sediment surface roughness.     

Comparative investigation of the detective quantum efficiency of direct and indirect conversion detector technologies in dedicated breast CT

PurposeTo investigate the dose saving potential of direct-converting CdTe photon-counting detector technology for dedicated breast CT.Materials and methodsWe analyzed the modulation transfer function (MTF), the noise power spectrum (NPS) and the detective quantum efficiency (DQE) of two detector technologies, suitable for breast CT (BCT): a flat-panel energy-integrating detector with a 70 μm and a 208 μm thick gadolinium oxysulfide (GOS) and a 150 μm thick cesium iodide (CsI) scintillator and a photon-counting detector with a 1000 μm thick CdTe sensor.ResultsThe measurements for GOS scintillator thicknesses of 70 μm and 208 μm delivered 10% pre-sampled MTF values of 6.6 mm⁻¹ and 3.2 mm⁻¹, and DQE(0) values of 23% and 61%. The 10% pre-sampled MTF value for the 150 μm thick CsI scintillator 6.9 mm⁻¹, and the DQE(0) value was 49%. The CdTe sensor reached a 10% pre-sampled MTF value of 8.5 mm⁻¹ and a DQE(0) value of 85%.ConclusionThe photon-counting CdTe detector technology allows for significant dose reduction compared to the energy-integrating scintillation detector technology used in BCT today. Our comparative evaluation indicates that a high potential dose saving may be possible for BCT by using CdTe detectors, without loss of spatial resolution.     

Characterizing Photothrombotic Distal Middle Cerebral Artery Occlusion and YAG Laser-Induced Reperfusion Model in the Izumo Strain of Spontaneously Hypertensive Rats

No study has systematically studied the relevance of original Izumo strain of spontaneously hypertensive rats (SHR/Izm) as a stroke model. Furthermore, both SHR/Izm and stroke-prone SHR/Izm (SHRSP/Izm) are commercially available, and recent progress in genetic studies allowed us to use several congenic strains of rats constructed with SHR/Izm and SHRSP/Izm as the genetic background strains. A total of 166 male SHR/Izm and 17 male SHRSP/Izm were subjected to photothrombotic middle cerebral artery (MCA) occlusion with or without YAG laser-induced reperfusion. The pattern of distal MCA was recorded. Infarct volumes were determined with 2,3,5-triphenyltetrazolium chloride. At 24 or 48 h after MCA occlusion, infarct volumes in the permanent occlusion and 2-h occlusion groups (88 ± 22 [SD] and 87 ± 25 mm³, respectively) were significantly larger than that in the 1-h occlusion group (45 ± 14 mm³), indicating the presence of sizeable zone of penumbra. Infarct size in SHRSP/Izm determined at 24 h after MCA occlusion was fairly large (124.0 ± 34.8 mm³, n = 10). Infarct volume in SHR/Izm with simple distal MCA was 76 ± 19 mm³, which was significantly smaller than 95 ± 22 mm³ in the other SHR/Izm with more branching MCA. These data suggest that this stroke model in SHR/Izm is useful in the preclinical testing of stroke therapies and elucidating the pathophysiology of cerebral ischemia/reperfusion.     

不同声强超声对孕鼠子宫收缩及胎鼠神经损伤的影响及机制

目的:探讨不同声强超声对孕鼠子宫收缩及胎鼠神经损伤的影响及机制。方法:将32只孕鼠随机分为A(0)组、B(2)组、C(4)组、D(8)组,每组各8只,分别接受声强为0 W cm~(-2)、2 W cm~(-2)、4 W cm~(-2)和8 W cm~(-2)的超声辐照20 min。记录孕鼠子宫收缩及子宫平滑肌ATP酶的活力,检测胎鼠大脑皮层与海马神经元凋亡及胆碱能神经系统相关酶的活力。结果:超声增加孕鼠子宫收缩频率、收缩幅度、收缩张力和子宫活动度(P均0.05),降低孕鼠子宫平滑肌中钠钾ATP酶、钙ATP酶和钙镁ATP酶的活性(P均0.05)。超声降低胎鼠大脑皮层和海马中Bcl~(-2)水平(P0.05),增加Bax和Caspase-3水平(P均0.05)。以及促进乙酰胆碱酯酶活力,降低乙酰胆碱和乙酰胆碱转移酶水平(P均0.05)。且4 W cm~(-2)和8 W cm~(-2)的超声比2 W cm~(-2)超声对这些指标的作用更强。结论:4 W cm~(-2)和8 W cm~(-2)超声可能通过降低ATP酶的活性促进孕鼠子宫平滑肌收缩,并可引起胎鼠大脑皮层和海马神经元损伤,机制可能与胆碱能神经元系统失衡有关,2 W cm~(-2)声强的超声对胎鼠神经元损伤甚小。     

Extracorporeal shock wave therapy decreases the number of total and degranulated mast cells and alleviates pelvic pain in a rat model of prostatitis

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain. Extracorporeal shock wave therapy (ESWT) has been used to treat patients with CP/CPPS, but the parameters used by ESWT are not uniformly determined. Herein, this study aims to assess the effects of ESWT with different energy flux densities on pelvic pain in CP/CPPS rats and to explore the mechanisms. A rat model of CP/CPPS was induced by intraprostatic injection of 1% carrageenan. ESWT with different energy flux densities (0.09, 0.20, 0.30, 0.40 mJ/mm²) was applied in the pelvic region of CP/CPPS rats once a week for 4 weeks. The results showed that compared with the other energy flux densities (0.09, 0.30, and 0.40 mJ/mm²), ESWT with 0.20 mJ/mm² exhibited a more powerful effect in alleviating pelvic pain and prostate damage. The therapeutic effect is associated with the reduction of the number of total and degranulated mast cells. Collectively, ESWT with 0.20 mJ/mm² achieved the optimal therapeutic effect in alleviating pelvic pain in CP/CPPS rats.

     

A novel LC‐MS/MS method to quantify eumelanin and pheomelanin and their relation to UVR sensitivity – A study on human skin biopsies

Melanin in the skin can be divided into eumelanin and pheomelanin subtypes. Simultaneous quantification of these subtypes could clarify their relation to skin type and skin cancer development. We describe a novel, sensitive liquid chromatography–tandem mass spectrometry method to quantify two eumelanin markers, pyrrole‐2,3,5‐tricarboxylic acid (PTCA) and pyrrole‐2,3‐dicarboxylic acid (PDCA), and two pheomelanin markers, thiazole‐4,5‐dicarboxylic acid (TDCA) and thiazole‐2,4,5 tricarboxylic acid (TTCA), performed in a single run using the same biopsy. Volunteers with either Fitzpatrick skin type (FST) I/II or III/IV (n = 30) each provided a 4‐mm punch biopsy from the buttock. Upon analysis, the FST I + II group had significantly less of all four melanin biomarkers (PTCA, 0.75 ng/mm²; PDCA, 0.08 ng/mm²; TTCA, 0.24 ng/mm²; and TDCA, 0.10 ng/mm²) versus the FST III + IV group (PTCA, 4.89 ng/mm²; PDCA, 0.22 ng/mm²; TTCA, 2.61 ng/mm²; and TDCA, 0.72 ng/mm²), p ≤ 0.003. We find that this new LC‐MS/MS method is sensitive enough to quantify eumelanin and pheomelanin markers even in the lightest skin types.     

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm². A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm². The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm². The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm². Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm² were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm² and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.     

An optimized calibration method for surface measurements with MOSFETs in shaped-beam radiosurgery

Nowadays MOSFET dosimeters are widely used for dose verification in radiotherapy procedures. Although their sensitive area satisfies size requirements for small field dosimetry, their use in radiosurgery has rarely been reported. The aim of this study is to propose and optimize a calibration method to perform surface measurements in 6 MV shaped-beam radiosurgery for field sizes down to 18 × 18 mm². The effect of different parameters such as recovery time between 2 readings, batch uniformity and build-up cap attenuation was studied. Batch uniformity was found to be within 2% and isocenter dose attenuation due to the build-up cap over the MOSFET was near 2% irrespective of field size. Two sets of sensitivity coefficients (SC) were determined for TN-502RD MOSFET dosimeters using experimental and calculated calibration; the latter being developed using an inverse square law model. Validation measurements were performed on a realistic head phantom in irregular fields. MOSFET dose values obtained by applying either measured or calculated SC were compared. For calibration, optimal results were obtained for an inter-measurement time lapse of 5 min. We also found that fitting the SC values with the inverse square law reduced the number of measurements required for calibration. The study demonstrated that combining inverse square law and Sterling–Worthley formula resulted in an underestimation of up to 4% of the dose measured by MOSFETs for complex beam geometries. With the inverse square law, it is possible to reduce the number of measurements required for calibration for multiple field–SSD combinations. Our results suggested that MOSFETs are suitable sensors for dosimetry when used at the surface in shaped-beam radiosurgery down to 18 × 18 mm².     

Capteur SAW implantable dédié à la télémesure de la température et de la pression artérielle : le projet ANR-TECSAN CIMPA

The CIMPA Project (2007-2008), led under the ANR-TECSAN Call, was coordinated by SENSeOR, in partnership with the LEAT and the FEMTO. The aim of the project was to develop a surface acoustic wave sensor demonstrator, passive implantable to monitoring the blood pressure and the temperature. This sensor uses the surface acoustic wave technology (SAW) and is composed of three resonators using quartz as piezoelectric substrate. One resonator for temperature measurement (T), a second resonator for the blood pressure measurement (P) and a third resonator, which is used as reference (R). This sensor is compatible with size requirements inherent to an implantation in an artery, since the size of the resonator with its antennas in its most compact configuration is of the order of 5.2 mm × 3.7 mm × 0.85 mm. It requires no embarked sources of energy and being able to be interrogated by a radiofréquence (RF) connection thanks to a transceiver, which emits a signal in the band industrial, scientific and medical (ISM). The sensor (connected to an integrated antenna on quartz of very small dimension) requested by the signal of interrogation emits in its turn a signal, which carries information of pressure and temperature. The transceiver then collects apart from its transmitting phase the signal emitted by the sensor and extracts by an appropriate signal processing method information of pressure and temperature. The targeted range for pressure measurement extends from 1 bar to 1.35 bar with an accuracy of about 2% FS.     

Evaluation of a SiPM array coupled to a Gd3Al2Ga3O12:Ce (GAGG:Ce) discrete scintillator

PurposeIn this study, we present the results of the evaluation of the SensL ArraySL-4 photo-detector, coupled to a 6 × 6 GAGG:Ce scintillator array, with 2 × 2 × 5 mm³ crystal size elements for possible applications in medical imaging detectors with focus in PET applications. Experimental evaluation was carried out with ²²Na and ¹³⁷Cs radioactive sources and the parameters studied were energy resolution and peak to valley ratio.MethodsArraySL-4 is a commercially available, 4 × 4 array detector covering an active area of 13.4 mm². The GAGG:Ce scintillator array used in this study has 0.1 mm thickness BaSO₄ reflector material between the crystal elements. A symmetric resistive voltage division matrix was applied, which reduces the 16 outputs of the array to 4 position signals. A Field Programmable Gate Array was used for triggering and digital processing of the signal pulses acquired using free running Analog to Digital Converters.ResultsRaw images and horizontal profiles of the 6 × 6 GAGG:Ce scintillator array produced under 511 keV and 662 keV excitation are illustrated. Moreover, the energy spectra obtained with ²²Na and ¹³⁷Cs radioactive sources from a single 2 × 2 × 5 mm³ GAGG:Ce scintillator are shown. The peak to valley ratio and the mean energy resolution values are reported.ConclusionsThe acquired raw image of the GAGG:Ce crystal array under 511 keV excitation shows a clear visualization of all discrete scintillator elements with a mean peak to valley ratio equal to 40. The mean energy resolution was measured equal to 10.5% and 9% respectively under 511 keV and 662 keV irradiation.     

Monte Carlo evaluation of occupational exposure during uterine artery embolization

PurposeUterine fibroids affect women mainly of childbearing age, an alternative for the treatment of these fibroids is uterine artery embolization (UAE), a minimally invasive procedure which uses fluoroscopy, providing radiation doses often high, due to the fact that professionals remain in the room throughout the procedure. In this work, equivalent and effective doses were evaluated for the main physician, for the assistant and for the patient during the UAE procedure.MethodsDoses were calculated using computer simulation with the Monte Carlo Method, and virtual anthropomorphic phantoms, in a typical scenario of interventional radiology with field sizes of 20 × 20, 25 × 25 and 32 × 32 cm², tube voltages of 70, 80, 90 and 100 kV, and projections of LAO45, RAO45 and PA.ResultsThe results showed that the highest doses received by the professionals were for the LAO45 projection with 32 × 32 cm² field size and 100 kV tube voltage, which is in accordance with the existing literature. The highest equivalent doses, without the protective equipment, were in the eyes, skin, breast and stomach for the main physician, and for the assistant they were in the eyes, breast, thyroid and skin. When she used the protective equipment, the highest equivalent doses for the main physician were on the skin, brain, bone marrow and bone surface, and for the assistant they were on the skin, brain, red bone marrow and bone surface.ConclusionsEffective doses increased up to 3186% for the main physician, and 2462% for the assistant, without protective equipment, thus showing their importance.     

Effects of maternal nutrient restriction followed by realimentation during midgestation on uterine blood flow in beef cows

The objective was to examine the effect of maternal nutrient restriction followed by realimentation during midgestation on uterine blood flow (BF). On Day 30 of pregnancy, lactating, multiparous Simmental beef cows were assigned randomly to treatments: control (CON; 100% National Research Council; n = 6) and nutrient restriction (RES; 60% of CON; n = 4) from Day 30 to 140 (period 1), and thereafter, realimented to CON until Day 198 of gestation (period 2). Uterine BF, pulsatility index (PI), and resistance index (RI) were obtained from both the ipsilateral and contralateral uterine arteries via Doppler ultrasonography. Generalized least square analysis was performed. Ipsilateral uterine BF in both groups increased quadratically (P < 0.01) during period 1 and linearly (P < 0.01) during period 2. There was a treatment (P = 0.05) effect during period 2; where RES cows had greater ipsilateral BF versus CON. Ipsilateral uterine PI and RI decreased linearly (P ≤ 0.01) during period 1 across treatments. Contralateral uterine BF in CON cows tended (P < 0.09) to be greater versus RES in both periods. Contralateral PI in both groups increased linearly (P ≤ 0.01) during period 1. Contralateral uterine RI was increased (P ≤ 0.05) in RES cows versus CON in both periods. There was no interaction or treatment effect (P ≥ 0.24) for total BF during either period. Nutrient restriction does not alter total uterine BF, but it may increase vascular resistance. However, up on realimentation, local conceptus-derived vasoactive factors appear to influence ipsilateral uterine BF.     

Cell proliferation and survival in the mating circuit of adult male hamsters: effects of testosterone and sexual behavior

The transient actions of gonadal steroids on the adult brain facilitate social behaviors, including reproduction. In male rodents, testosterone acts in the posterior medial amygdala (MeP) and medial preoptic area (MPOA) to promote mating. Adult neurogenesis occurs in both regions. The current study determined if testosterone and/or sexual behavior promote cell proliferation and survival in MeP and MPOA. Two experiments were conducted using the thymidine analog BrdU. First, gonad-intact and castrated male hamsters (n = 6/group) were compared 24 h or 7 weeks after BrdU. In MeP, testosterone-stimulated cell proliferation 24 h after BrdU (intact: 22.8 ± 3.9 cells/mm², castrate: 13.2 ± 1.4 cells/mm²). Testosterone did not promote cell proliferation in MPOA. Seven weeks after BrdU, cell survival was sparse in both regions (MeP: 2.5 ± 0.6 and MPOA: 1.7 ± 0.2 cells/mm²), and was not enhanced by testosterone. In Experiment 2, gonad-intact sexually-experienced animals were mated weekly to determine if regular neural activation enhances cell survival 7 weeks after BrdU in MeP and MPOA. Weekly mating failed to increase cell survival in MeP (8.1 ± 1.6 vs. 9.9 ± 3.2 cells/mm²) or MPOA (3.9 ± 0.7 vs. 3.4 ± 0.3 cells/mm²). Furthermore, mating at the time of BrdU injection did not stimulate cell proliferation in MeP (8.9 ± 1.7 vs. 8.1 ± 1.6 cells/mm²) or MPOA (3.6 ± 0.5 vs. 3.9 ± 0.7 cells/mm²). Taken together, our results demonstrate a limited capacity for neurogenesis in the mating circuitry. Specifically, cell proliferation in MeP and MPOA are differentially influenced by testosterone, and the birth and survival of new cells in either region are not enhanced by reproductive activity.     

Vascularization of broad ligament of uterus and its relationship with fetal and placental development in gilts

The objective of this study was to evaluate the influence of vascular architecture of broad ligament of the uterus on fetal and placental development in gilts. Fifteen gilts DB-90 (DanBred) were divided into three groups according to gestational age at slaughter (50, 80, and 106 days). After slaughter, fetuses and placentas were collected, weighed, and measured. The uterine arterial system was detached by latex repletion for quantification of the number and diameter of the terminal vessels in different regions of the uterine horns (apex, middle region, and base). Fetal and placental measurements were statistically analyzed and correlated with the number and diameter of arteries in each uterine segment. No correlation was observed (P > 0.10) between the number and diameter of arteries destined to the uterus with the number or weight of fetuses or placental weight in any gestational group. It was observed (P < 0.05) that more vessels destined to the medium region of the uterine horns, independent of the gestational age or uterus side. At the 80th day of gestation, fetuses located at the base of the uterus have (P < 0.05) smaller cephalic and thoracic perimeters. It was concluded that there were differences in vascularization of broad ligament that irrigates the different uterine segments, but this was not sufficient to influence the development of fetuses in gilts. The middle region of the uterine horns was the segment with a greater number of vessels, regardless of gestational age.     

Ductus arteriosus: Developmental response to oxygen and indomethacin

It has been suggested that ineffective constriction in response to an increase in PO₂ is the primary cause for delayed closure of the ductus arteriosus in preterm infants. We studied the isometric contractile effects of increased PO₂ and indomethacin on isolated rings of lamb ductus arteriosus from animals of different gestational ages (87 to 147 days, term is 150 days). Rings from animals less than 110 days have a significantly smaller oxygen-induced contraction (2.53 ± .30 g/mm², n = 16) when compared with rings from animals near term (4.59 ± .69 g/mm², n = 9). Oxygen contracted rings from all gestational ages contract further upon addition of 1 μg/ml indomethacin. Rings from animals less than 110 days have a significantly larger indomethacin induced contraction (1.10 ± .17 g/mm², n = 16) than vessels near term (0.52 ± .12 g/mm², n = 9). Inhibition of prostaglandin production in rings less than 110 days results in a total combined oxygen and indomethacin induced tension that is not significantly different from the oxygen or oxygen and indomethacin induced tension developed in rings from animals near term. This is consistent with the hypothesis that, early during gestation, endogenous prostaglandins inhibit the vessel's ability to contract in response to oxygen. These observations are also consistent with the ability of indomethacin to constrict the patient ductus arteriosus in pre-term infants.     

Multipurpose Love acoustic wave immunosensor for bacteria,virus or proteins detection

A multipurpose Love acoustic wave biosensor is described in this article. As mass loading is one of the main effect involved in acoustic wave sensors, a great range of biomolecules could be detected using such sensors. In this way, the antibody/antigen binding property was used to immobilise the target species. We first compared different coupling agents to link the antibodies sensitive layer to the SiO₂ sensor surface. Results showed that GPTS monolayer, allowing covalent attachment of antibodies bioreceptors, is better suited than DTSP and protein G. It permits to obtain a dense, stable and reproducible sensitive layer of antibodies. Then, different biological species with different size and shape like proteins, bacteriophages or bacteria were detected using such sensor. Different models have been chosen to validate the effective detection of a large species range: an anti-mouse antibody has been used to simulate small molecules (< 10 nm) like proteins or toxins, bacteriophage M13 for species lower than 1 μm like virus, and Escherichia coli for bacteria which are typically longer than 1 μm. Each kind of species were successfully quickly detected from few seconds for small proteins to one hour for bacteria, with detection threshold down to 4 ng/mm² for protein and 10⁶ cfu per milliliter for bacteria.     

Uterine artery blood flow remains unchanged in pregnant mares in response to short-term administration of pentoxifylline

The objective of this study was to use Doppler ultrasound technology to determine whether pentoxifylline administration increased uterine blood flow in normal pregnant pony mares. Thirteen pregnant pony mares between 18 and 190 d of gestation (mean ± SEM, 101 ± 55) were utilized for the study during two trial periods. In each trial, pentoxifylline (17 mg/kg by mouth every 12h, diluted in syrup) was administered to half of the mares for 3 d, while the other mares were treated with syrup only. Doppler measurements were obtained from the right and left uterine arteries from each mare for 2 d prior to treatment and throughout the treatment period. The mean Resistivity Index (RI), Pulsatility Index (PI), Uterine Artery Diameter (D), and Total Arterial Blood Flow (TABF) from each day were compared over time and between groups. Administration of pentoxifylline did not alter uterine blood flow parameters compared with controls (values for all treatment days combined were RI: 0.517 ± 0.014 vs 0.543 ± 0.016; PI: 0.876 ± 0.048 vs 0.927 ± 0.057; D: 0.388 ± 0.018 vs 0.379 ± 0.023 cm; and TABF: 35.26 ± 7.38 vs 30.73 ± 5.29 mL/min). Uterine blood flow increased over the course of the 5 d study, irrespective of treatment, and was higher in mares of greater gestational age than in early gestational mares (RI: r² = 0.35; PI: r² = 0.37; D: r² = 0.66; and TABF: r² = 0.67 - P < 0.00001). We concluded that any immediate benefits of pentoxifylline administration in the pregnant mare were not mediated through enhanced uterine artery blood flow.     

Metastasis‐specific patterns of response and progression with anti‐PD‐1 treatment in metastatic melanoma

This study evaluated patterns of response as discerned by comprehensive metastasis‐specific analysis in metastatic melanoma patients receiving anti‐PD‐1 antibodies. Bi‐dimensional measurements of every metastasis in patients enrolled in the KEYNOTE‐001 trial at a single institution were obtained at baseline and throughout treatment. Twenty‐seven evaluable patients had 399 baseline metastases measurable on CT imaging. Complete response (CR) which occurred in 52.6% of metastases was smaller (mean 223 mm² versus 760 mm², p < .01) and occurred more frequently in the lungs (65% versus 39.4%, p < .01). Response was heterogenous (new/progressing metastases alongside CR metastases) at first assessment in 4/14 patients with objective response (OR) as opposed to 7/13 patients with non‐OR. CR of individual metastases is common and influenced by site and size. Most patients with OR demonstrate homogenous regression in all metastases at the first assessment. In contrast, patients with early heterogeneity had a poor outcome.     

Comparison of the action of La3+ and Ca2+ on contraction threshold and other membrane parameters of frog skeletal muscle

Summary The influence of La³⁺ on contraction threshold, on membrane input resistance, and on action potential parameters was investigated in fibers of the sartorius muscle of the frog, and it was compared to that of Ca²⁺. The dependence of the contraction threshold on [La³⁺]₀ in the presence of 0.5mm Ca²⁺ gave a sigmoid relationship between 0.1 and 5mm La³⁺ with a shift of 23 to 34 mV to less negative potentials following a 10-fold increase of [La³⁺]₀. The membrane input resistance was increased to various degrees in La-containing solutions, the increase beingirreversible. The threshold of action potential generation was shifted to less negative potentials by 28 mV, and the duration at half-maximal amplitude was tripled by 0.5mm La³⁺. In comparison a 10-fold increase of [Ca²⁺]₀ in the range of 0.5 to 50mm shifted the contraction threshold by 15 mV to less negative potentials. 17mm Ca²⁺, a concentration having the same effect on contraction threshold as 0.5mm La³⁺, increased membrane input resistancereversibly, shifted the action potential threshold by 16 mV to less negative potentials, and had only minor effects on action potential duration. Conduction was never blocked by Ca²⁺ as it was with 1mm La³⁺. In a theoretical treatment, it is shown that the influence of Ca²⁺ on contraction threshold, butnot that of La³⁺, may be accounted for by its screening and binding to negative surface charges according to the Gouy-Chapman theory of the diffuse double layer. To describe the action of La³⁺ on the contraction threshold an additional interaction of La³⁺ with neutral but amphoteric sites was considered.     

Relationship of sperm small heat-shock protein 10 and voltage-dependent anion channel 2 with semen freezability in boars

Freezability differences between boar ejaculates exist, but there is no useful method to predict the ejaculate freezability before sperm cryopreservation takes place. In this context, the present study sought to determine whether the amounts of small heat-shock protein 10 (also known as outer dense fiber protein 1) (ODF1/HSPB10) and voltage-dependent anion channel 2 (VDAC2) may be used as boar sperm freezability markers. With this aim, 26 boar ejaculates were split into two fractions: one for protein extraction and the other for cryopreservation purposes. Ejaculates were subsequently classified into two groups (good freezability ejaculates [GFE] and poor freezability ejaculates [PFE]) based on viability and sperm motility assessments after 30 and 240 minutes of after thawing. Although the VDAC2 amounts, analyzed through Western blot, were significantly higher (P < 0.01) in GFE (1.15 ± 0.18 density mm²) than in PFE (0.16 ± 0.03 density mm²), no significant differences were observed in ODF1/HSPB10 between both groups (i.e., 1.97 ± 0.38 density mm² in GFE vs. 1.87 ± 1.54 density mm² in PFE). In addition, principal component and multiple regression analyses indicated that the component explaining most of the variance (78.41%) in ejaculate freezability at 240 minutes after thawing resulted to be significantly (P < 0.05) correlated with VDAC2 content. This result revealed that the amounts of VDAC2 but not those of ODF1/HSPB10 may be used to predict the freezability of a given boar ejaculate before starting cryopreservation procedures.