Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation.

The course of normal development and response to pathology are strongly influenced by biological sex. For instance, female childhood cancer survivors who have undergone cranial radiation therapy (CRT) tend to display more pronounced cognitive deficits than their male counterparts. Sex effects can be the result of sex chromosome complement (XX vs. XY) and/or gonadal hormone influence. The contributions of each can be separated using the four-core genotype mouse model (FCG), where sex chromosome complement and gonadal sex are decoupled. While studies of FCG mice have evaluated brain differences in adulthood, it is still unclear how sex chromosome and sex hormone effects emerge through development in both healthy and pathological contexts. Our study utilizes longitudinal MRI with the FCG model to investigate sex effects in healthy development and after CRT in wildtype and immune-modified Ccl2-knockout mice. Our findings in normally developing mice reveal a relatively prominent chromosome effect prepubertally, compared to sex hormone effects which largely emerge later. Spatially, sex chromosome and hormone influences were independent of one another. After CRT in Ccl2-knockout mice, both male chromosomes and male hormones similarly improved brain outcomes but did so more separately than in combination. Our findings highlight the crucial role of sex chromosomes in early development and identify roles for sex chromosomes and hormones after CRT-induced inflammation, highlighting the influences of biological sex in both normal brain development and pathology.

Effects and action mechanism of gonadotropins on ovarian follicular cells: A novel role of Sphingosine-1-Phosphate (S1P). A review.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control antral follicular growth by regulating several processes, such as the synthesis of hormones and signaling molecules, proliferation, survival, apoptosis, luteinization, and ovulation. To exert these effects, gonadotropins bind to their respective Gs protein-coupled receptors, activating the protein kinase A (PKA) pathway or recruiting Gq proteins to activate protein kinase C (PKC) signaling. Although the action mechanism of FSH and LH is clear, recently, it has been shown that both gonadotropins promote the synthesis of sphingosine-1-phosphate (S1P) in granulosa and theca cells through the activation of sphingosine kinase 1. Moreover, the inhibition of SPHKs reduces S1P synthesis, cell viability, and the proliferation of follicular cells in response to gonadotropins, and the addition of S1P to the culture medium increases the proliferation of granulosa and theca cells without apparent effects on sexual steroid synthesis. Therefore, we consider that S1P is a crucial signaling molecule that complements the canonical gonadotropin pathway to promote the proliferation and viability of granulosa and theca cells.

Exercise promotes growth and rescues volume deficits in the hippocampus after cranial radiation in young mice.

Human and animal studies suggest that exercise promotes healthy brain development and function, including promoting hippocampal growth. Childhood cancer survivors that have received cranial radiotherapy exhibit hippocampal volume deficits and are at risk of impaired cognitive function, thus they may benefit from regular exercise. While morphological changes induced by exercise have been characterized using magnetic resonance imaging (MRI) in humans and animal models, evaluation of changes across the brain through development and following cranial radiation is lacking. In this study, we used high-resolution longitudinal MRI through development to evaluate the effects of exercise in a pediatric mouse model of cranial radiation. Female mice received whole-brain radiation (7 Gy) or sham radiation (0 Gy) at an infant equivalent age (P16). One week after irradiation, mice were housed in either a regular cage or a cage equipped with a running wheel. In vivo MRI was performed prior to irradiation, and at three subsequent timepoints to evaluate the effects of radiation and exercise. We used a linear mixed-effects model to assess volumetric and cortical thickness changes. Exercise caused substantial increases in the volumes of certain brain regions, notably the hippocampus in both irradiated and nonirradiated mice. Volume increases exceeded the deficits induced by cranial irradiation. The effect of exercise and irradiation on subregional hippocampal volumes was also characterized. In addition, we characterized cortical thickness changes across development and found that it peaked between P23 and P43, depending on the region. Exercise also induced regional alterations in cortical thickness after 3 weeks of voluntary exercise, while irradiation did not substantially alter cortical thickness. Our results show that exercise has the potential to alter neuroanatomical outcomes in both irradiated and nonirradiated mice. This supports ongoing research exploring exercise as a strategy for improving neurocognitive development for children, particularly those treated with cranial radiotherapy.

Impact of implant thread design on insertion torque and osseointegration: a preclinical model.

BACKGROUND: Successful osseointegration of endosteal dental implants has been attributed to implant design, including the macro-, micro- and nano- geometric properties. Based on current literature pertaining to implant design, the resultant cellular and bone healing response is unknown when the thread thickness of the implants is increased, resulting in an increased contact area in implants designed with healing chambers. The aim of this study was to evaluate the effect of two implant designs with different thread profiles on the osseointegration parameters and implant stability at 3- and 6-weeks in vivo using a well-established preclinical dog model. MATERIAL AND METHODS: A total of 48 type V Ti alloy implants were divided in two groups according to their thread design (D1= +0.1x/mm and D2= +0.15x/mm) and placed in an interpolated fashion into the radii of six beagles. Insertion torque was measured at time of placement, radii were extracted for histological processing following 3- and 6-week healing intervals. Histologic and histomorphometric analyses were performed in terms of bone to implant contact (%BIC) and bone area fraction occupancy within implant threads (%BAFO). Statistical analyses were performed through a linear mixed model with fixed factors of time and implant thread design. RESULTS: Surface roughness analysis demonstrated no significant differences in Sa and Sq between D1 and D2 implant designs, which confirmed that both implant designs were homogenous except for their respective thread profiles. For insertion torque, statistically significant lower values were recorded for D1 in comparison to D2 (59.6 ± 11.1 and 78.9 ± 10.1 N⋅cm, respectively). Furthermore, there were no significant differences with respect to histological analysis and histomorphometric parameters, between D1 and D2 at both time points. CONCLUSIONS: Both thread profiles presented equivalent potential to successfully osseointegrate in the osteotomies, with D2 yielding higher mechanical retention upon placement without detrimental bone resorption.

Percutaneous closure of a ruptured right coronary sinus of Valsalva aneurysm that mimics severe aortic regurgitation.

A 34-year-old male was admitted with presumed acute, severe aortic regurgitation. Multimodal imaging was performed and showed a ruptured right coronary sinus of Valsalva aneurysm into the right atrium. He underwent a percutaneous closure of the ruptured sinus of Valsalva aneurysm. The patient had major clinical improvement.

Entropy, purity and optical hysteresis in markovian optical modes.

We describe the synthesis of optical modes whose axial structure follows a random tandem array of Bessel beams of integer order. The array follows fluctuations of Markov-chain type and the amplitude values for each beam are linked to a sequence of random vectors. As a prototype, we describe the synthesis of optical fields for Markov-chain type Ehrenfest. This process models the thermodynamic equilibrium and then it can be related to the evolution and stability of optical systems, in this way, it offers a similitude with partially coherent processes where the coherence degree is now distributed between all the compounds of the resulting random vector. The matrix representation for the stochastic process allows incorporating entropy properties and the calculus of the purity for the optical field. This constitutes the basis to describe the interference between markovian modes. When the set of markovian modes type Ehrenfest reaches a stable configuration they become indistinguishability non-conservative optical field having associated hysteresis features. Computer simulations are presented.

The influence of high-density lipoprotein (HDL) and HDL subfractions on insulin secretion and cholesterol efflux in pancreatic derived ß-cells.

BACKGROUND: High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the ß-cell line MIN-6. METHODS: We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line. RESULTS: Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux. CONCLUSIONS: HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.

The -514C>T polymorphism in the LIPC gene modifies type 2 diabetes risk through modulation of HDL-cholesterol levels in Mexicans.

PURPOSE: Both type 2 diabetes (T2D) and low levels of high-density lipoprotein cholesterol (HDL-C) are very prevalent conditions among Mexicans. Genetic variants in the LIPC gene have been associated with both conditions. This study aimed to evaluate the association of the -514C < T (rs1800588) LIPC gene polymorphism with different metabolic traits, particularly the effects of this polymorphism on HDL-C plasma levels and T2D risk. METHODS: Mediation analysis was used to assess the direct and indirect effects of the -514C>T LIPC gene variant on HDL-C levels, T2D risk, and body mass index (BMI), in 2105 Mexican mestizo participants. We also assessed the functional effect of the -514C>T LIPC variant on the promoter activity of a reporter gene in the HepG2 cell line. RESULTS: Direct effects show that the -514C>T LIPC polymorphism is significantly associated with increased HDL-C plasma levels (ß = 0.03; p < 0.001). The -514C>T variant resulted in an indirect protective effect on T2D risk through increasing HDL-C levels (ß = - 0.03; p < 0.001). Marginal direct association between -514C>T and T2D was found (ß = 0.08; p = 0.06). Variables directly influencing T2D status were European ethnicity (ß = - 7.20; p < 0.001), age (ß = 0.04; p < 0.001), gender (ß = - 0.15; p = 0.017) and HDL-C (ß = - 1.07; p < 0.001). In addition, we found that the -514C>T variant decreases the activity of LIPC promoter by 90% (p < 0.001). CONCLUSIONS: The -514C>T polymorphism was not directly associated with T2D risk. HDL-C acts as a mediator between -514C>T LIPC gene variant and T2D risk in the Mexican population.

R230C but not - 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels.

PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.

Invariant correlated optical fields driven by multiplicative noise.

We describe the evolution of a linear transmittance when it is perturbed with multiplicative noise; the evolution is approximated through an ensemble of random transmittances that are used to generate diffraction fields. The randomness induces a competition mechanism between noise and transmittance, and it is identified through the self-correlation function. We show that the geometry of the self-correlation function is a single peak preserved in the diffraction field that can be matched with localization-like effects. To corroborate the theoretical predictions, we perform an experiment using a linear grating where the noise is approximated by a stochastic Markov chain. Experimental results are shown.

Oviductal Proteins Effect in Rooster Spermatic Cryopreservation.

BACKGROUND: Cryopreservation induces spermatic cryo capacitation, which can decrease thawed sperm fertilizing capability. OBJECTIVE: To evaluate the effect of uterus-vaginal union protein factors to inhibit sperm cryo capacitation and maintain viability and fertilizing capability of rooster spermatozoa. MATERIALS AND METHODS: Rooster spermatozoa was cryopreserved using Lake extender supplemented with different hen's uterus-vaginal junction protein concentrations, to determine spermatic viability, sperm physiological condition and fertilizing capability in vivo. RESULTS: It was possible to induce spermatic decapacitation in vitro, inhibiting cryo capacitation and allowing fertility results comparable to those obtained with fresh semen. CONCLUSION: Uterus-vaginal protein extracts induce spermatic decapacitation in vitro.

Quantitative analysis of the interplay between InAs quantum dots and wetting layer during the GaAs capping process.

A procedure to quantitatively analyse the relationship between the wetting layer (WL) and the quantum dots (QDs) as a whole in a statistical way is proposed. As we will show in the manuscript, it allows determining, not only the proportion of deposited InAs held in the WL, but also the average In content inside the QDs. First, the amount of InAs deposited is measured for calibration in three different WL structures without QDs by two methodologies: strain mappings in high-resolution transmission electron microscopy images and compositional mappings with ChemiSTEM x-ray energy spectrometry. The area under the average profiles obtained by both methodologies emerges as the best parameter to quantify the amount of InAs in the WL, in agreement with high-resolution x-ray diffraction results. Second, the effect of three different GaAs capping layer (CL) growth rates on the decomposition of the QDs is evaluated. The CL growth rate has a strong influence on the QD volume as well as the WL characteristics. Slower CL growth rates produce an In enrichment of the WL if compared to faster ones, together with a diminution of the QD height. In addition, assuming that the QD density does not change with the different CL growth rates, an estimation of the average In content inside the QDs is given. The high Ga/In intermixing during the decomposition of buried QDs does not only trigger a reduction of the QD height, but above all, a higher impoverishment of the In content inside the QDs, therefore modifying the two most important parameters that determine the optical properties of these structures.

Modular control of gait after incomplete spinal cord injury: differences between sides.

STUDY DESIGN: This is an analytical descriptive study. OBJECTIVES: The main goal of this study was to compare the modular organization of bilateral lower limb control in incomplete spinal cord injury (iSCI) patients during overground walking, using muscle synergies analysis. The secondary goal was to determine whether the similarity between the patients and control group correlate with clinical indicators of walking performance. SETTING: This study was conducted in National Hospital for Spinal Cord Injury (Toledo, Spain). METHODS: Eight iSCI patients and eight healthy subjects completed 10 walking trials at matched speed. For each trial, three-dimensional motion analysis and surface electromyography (sEMG) analysis of seven leg muscles from both limbs were performed. Muscle synergies were extracted from sEMG signals using a non-negative matrix factorization algorithm. The optimal number of synergies has been defined as the minimum number needed to obtain variability accounted for (VAF) ⩾90%. RESULTS: When compared with healthy references, iSCI patients showed fewer muscle synergies in the most affected side and, in both sides, significant differences in the composition of synergy 2. The degree of similarity of these variables with the healthy reference, together with the composition of synergy 3 of the most affected side, presented significant correlations (P<0.05) with walking performance. CONCLUSION: The analysis of muscle synergies shows potential to detect differences between the two sides in patients with iSCI. Specifically, the VAF may constitute a new neurophysiological metric to assess and monitor patients' condition throughout the gait recovery process.

Adaptable Optical Fiber Displacement-Curvature Sensor Based on a Modal Michelson Interferometer with a Tapered Single Mode Fiber.

A compact, highly sensitive optical fiber displacement and curvature radius sensor is presented. The device consists of an adiabatic bi-conical fused fiber taper spliced to a single-mode fiber (SMF) segment with a flat face end. The bi-conical taper structure acts as a modal coupling device between core and cladding modes for the SMF segment. When the bi-conical taper is bent by an axial displacement, the symmetrical bi-conical shape of the tapered structure is stressed, causing a change in the refractive index profile which becomes asymmetric. As a result, the taper adiabaticity is lost, and interference between modes appears. As the bending increases, a small change in the fringe visibility and a wavelength shift on the periodical reflection spectrum of the in-fiber interferometer is produced. The displacement sensitivity and the spectral periodicity of the device can be adjusted by the proper selection of the SMF length. Sensitivities from around 1.93 to 3.4 nm/mm were obtained for SMF length between 7.5 and 12.5 cm. Both sensor interrogations, wavelength shift and visibility contrast, can be used to measure displacement and curvature radius magnitudes.

Short-term methionine supplementation during the early post-partum period in primiparous rabbits improves prolificacy associated with an increase in serum concentrations of IGF-I.

The aim of this study was to evaluate the effects of methionine supplementation on energy metabolism and reproductive performance during the early post-partum period in primiparous does. Forty nulliparous New Zealand White does were used. Females were randomized in two groups at calving: the control group (n = 20) was fed with the basal diet, and the methionine group (n = 20) was fed the basal diet plus 1 g/animal/day of methionine from the day of calving to 4 days post-partum. Results showed that methionine supplementation increased (p = 0.032) the concentration of insulin-like growth factor-1 with respect to control group 4 days post-partum. It similarly increased the prolificacy (p = 0.03), the number of kits born alive per litter (p = 0.06) and the body gain weight of the litter during supplementation (p = 0.035). These results were observed despite the does in the methionine group having a deeper negative energy balance than the does in the control group. Finally, methionine supplementation did not affect receptivity (p = 0.23), fertility (p = 0.49), the number of kits born dead per litter (p = 0.86) insulin and metabolites as glucose, non-esterified fatty acids and triglycerides. In conclusion, our results show that methionine supplementation during the first 4 days of the post-partum period in rabbits increases total litter size and the corporal weight of kits and is associated with an increase in blood concentration of IGF-1.

Short-term dietary concentrate supplementation during estrus synchronization treatment in beef cows increased IGF-I serum concentration but did not affect the reproductive response.

The objective of this study was to evaluate if short-term dietary concentrate supplementation increased IGF-I serum concentration and resulted in a reproductive response during estrus synchronization treatment in non-lactating beef cows. Thirty non-lactating beef cows (Bos indicus × Bos taurus) were allocated to the same pastureland and fed native tropical grasses as a basal diet. Cows were synchronized using a 7-day CO-Synch plus controlled internal drug release (CIDR) protocol and received fixed time artificial insemination (FTAI). Cows were divided into two groups; the control group (n = 16) received 0.5 kg of concentrate/cow/day, whereas the supplemented group (n = 14) received 4.0 kg of concentrate/cow/day. The period of supplementation was 10 days from the day of CIDR insert to FTAI. The concentration of IGF-I increased (P < 0.05) in the supplemented group, while no significant changes were observed in the control group. Moreover, at the time of insemination, IGF-I serum concentrations were higher in supplemented cows compared with control cows (P < 0.05). Notably, metabolite and insulin concentrations did not differ (P > 0.05) between treatment groups or sampling day. The response to estrus induction, measured as estrus presentation, ovulation rate, and pregnancy rate, was similar between experimental groups (P > 0.05). In conclusion, our results indicated that supplementation with dietary concentrate for 10 days in non-lactating beef cows changed the endocrine milieu, specifically increasing IGF-I serum concentration. However, these endocrine changes did not affect response to estrous induction treatment.

[Chronic skin ulcer in a 24-year-old man after a journey to Southeast Asia]. / Chronisches Ulkus nach Südostasienreise bei 24­jährigem Mann.

Our report concerns a 24-year-old man with a chronic exsudative skin lesion after a journey to Southeast Asia. The diagnosis of melioidosis was made by the identification of Burkholderia pseudomallei from the ichor. The diagnosis was confirmed by polymerase change reaction. The patient was treated with meropenem i. v. for about 10 days and with trimethoprim/sulfamethoxazole for the following 12 weeks. Melioidosis is an endemic disease in Southeast Asia and North Australia which in some cases can run a severe course and can have a high fatality rate. The relevance of melioidosis becomes more important against the background of the increasing global movement of travelers and migration.

Post-fundoplication symptoms and complications: Diagnostic approach and treatment. / Síntomas y complicaciones posfunduplicatura: abordaje diagnóstico y tratamiento.

Laparoscopic Nissen fundoplication is currently considered the surgical treatment of choice for gastroesophageal reflux disease (GERD) and its long-term effectiveness is above 90%. Adequate patient selection and the experience of the surgeon are among the predictive factors of good clinical response. However, there can be new, persistent, and recurrent symptoms after the antireflux procedure in up to 30% of the cases. There are numerous causes, but in general, they are due to one or more anatomic abnormalities and esophageal and gastric function alterations. When there are persistent symptoms after the surgical procedure, the surgery should be described as "failed". In the case of a patient that initially manifests symptom control, but the symptoms then reappear, the term "dysfunction" could be used. When symptoms worsen, or when symptoms or clinical situations appear that did not exist before the surgery, this should be considered a "complication". Postoperative dysphagia and dyspeptic symptoms are very frequent and require an integrated approach to determine the best possible treatment. This review details the pathophysiologic aspects, diagnostic approach, and treatment of the symptoms and complications after fundoplication for the management of GERD.

Mechanism-based combination treatment dramatically increases therapeutic efficacy in murine globoid cell leukodystrophy.

Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations.

Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry.

Ex vivo magnetic resonance imaging (MRI) requires chemical fixation to preserve tissue during storage or extended imaging sessions. Although it is commonly understood that fixation may alter tissue volume and shape, the potential confounding effects of fixation and storage on morphometric analyses have not been well characterized. With increasing use of ex vivo MRI for mouse brain phenotying and opportunities for inter-study comparisons, we sought to characterize how changes in fixation and/or storage times affected tissue volume, and how this might impact phenotyping results. Mouse brain samples that had been perfusion fixed, within the skull as per our standard protocol, were immersed in formaldehyde-based fixative for 1 to 5days before being stored in saline or water. Throughout fixation and storage, samples were repeatedly scanned using magnetic resonance imaging, and analyzed for volume expansion or shrinkage. We found that most of the brain continued to shrink post fixation, with the rate of shrinkage dependent on the solution in which the samples were submerged. Maximum changes in volume of 3.5% per day and 3% per month were detected during fixation and storage (in PBS), respectively. Most notably, changes were non-uniform, with some structures shrinking slower, or even expanding, when compared to other structures in the brain. Our results highlight that caution is necessary when interpreting results from experiments with inconsistent fixation and storage protocols, so as not to mistake these changes for phenotypic differences.