Artificial intelligence and colon capsule endoscopy: development of an automated diagnostic system of protruding lesions in colon capsule endoscopy.

BACKGROUND: Colon capsule endoscopy (CCE) is a minimally invasive alternative for patients unwilling to undergo conventional colonoscopy, or for whom the latter exam is contraindicated. This is particularly important in the setting of colorectal cancer screening. Nevertheless, these exams produce large numbers of images, and reading them is a monotonous and time-consuming task, with the risk of overlooking important lesions. The development of automated tools based on artificial intelligence (AI) technology may improve some of the drawbacks of this diagnostic instrument. METHODS: A database of CCE images was used for development of a Convolutional Neural Network (CNN) model. This database included anonymized images of patients with protruding lesions in the colon or patients with normal colonic mucosa or with other pathologic findings. A total of 3,387,259 frames from 24 CCE exams were retrospectively reviewed. For CNN development, 3640 images (860 protruding lesions and 2780 with normal mucosa or other findings) were ultimately extracted. Training and validation datasets were constructed for the development and testing of the CNN. RESULTS: The CNN detected protruding lesions with a sensitivity, specificity, positive and negative predictive values of 90.7, 92.6, 79.2 and 96.9%, respectively. The area under the receiver operating characteristic curve for detection of protruding lesions was 0.97. CONCLUSIONS: The deep learning algorithm we developed is capable of accurately detecting protruding lesions. The application of AI technology to CCE may increase its diagnostic accuracy and acceptance for screening of colorectal neoplasia.

Preparation and evaluation of caffeine bioadhesive emulgels for cosmetic applications based on formulation design using QbD tools.

OBJECTIVE: The aim of the present study was to evaluate the influence of the incorporation of caffeine as a model active ingredient on the quality attributes of a bioadhesive emulgel formulation previously optimized by Quality by Design (QbD) tools. Emulgels are emerging topical drug delivery systems for cosmetic or pharmaceutical uses, which combine the advantages of both emulsions and gels. METHODS: In this work, the observed and predicted values for spreadability, phase separation by centrifugation and detachment forces performed by texturometer were compared with those of the control and active-containing emulgel formulations. In addition, rheological properties, release of caffeine and comparative in vitro/ex vivo bioadhesion properties were evaluated using human skin. RESULTS: The flow curves of emulgel formulations showed the typical pseudoplastic and no thixotropic flow with yield stress. The incorporation of active ingredient did not produce significant changes. All emulgels were uniformly spread and no significant differences in spreadability values between control and caffeine containing formulations and neither respect to those predicted values from experimental design optimization were found. Emulgel formulations showed appropriate detachment forces values and no significant differences between caffeine loading and control emulgel formulations were observed. CONCLUSION: Caffeine was successfully vehiculized in this optimized bioadhesive emulgel formulation, which showed high robustness regarding the process variability. There were no significant changes in the critical quality attributes after the incorporation of the active ingredient and a promising stability was observed for at least one year. Results suggested that the optimized emulgel is an interesting topical biodhesive delivery system for cosmetic applications, including agents for skin conditioning, not present in gels formulations.

OBJECTIF: la présente étude visait à évaluer l'influence de l'incorporation de la caféine comme une substance active modèle dans les attributs de qualité d'une préparation d'émulgel bioadhésif préalablement optimisée grâce à des outils QbD (Quality by Design, Qualité par la conception). Les émulgels sont des systèmes d'administration de médicaments topiques émergents destinés à des usages cosmétiques ou pharmaceutiques, qui associent les avantages des émulsions et des gels. MÉTHODES: dans cet étude, les valeurs observées et prédites en matière d'étalement, de séparation des phases par centrifugation et de forces de détachement par texturomètre ont été comparées à celles des préparations de contrôle et d'émulgel contenant des actifs. En outre, les propriétés rhéologiques, la libération de caféine et la comparaison des propriétés de bioadhérence in vitro / ex vivo ont été évaluées sur la peau humaine. RÉSULTATS: les courbes de débit des préparations d'émulgel révèlent un flux pseudoplastique typique et non thixotropique avec charge d'écoulement. L'incorporation de la substance active n'a pas produit de changements importants. Tous les émulgels ont été uniformément étalés et aucune différence significative dans les valeurs d'étalement entre les préparations de contrôle et celles contenant de la caféine n'a été observée. Aucune différence concernant les valeurs prédites dans l'optimisation de la conception expérimentale n'a été observée. Les préparations d'émulgel ont montré des valeurs de forces de détachement appropriées et aucune différence significative n'a été observée entre les préparations d'émulgel à base de caféine et les préparations de contrôle. CONCLUSION: la caféine a été administrée avec succès dans cette préparation optimisée d'émulgel bioadhésif, qui a affiché une grande résistance en ce qui concerne la variabilité du procédé. Il n'y a pas eu de changement significatif dans les attributs de qualité critiques après l'incorporation de la substance active et une stabilité prometteuse a été observée pendant au moins un an. Les résultats ont suggéré que l'émulgel optimisé est un système d'administration de bioadhérence topique intéressant pour les applications cosmétiques, y compris les agents de revitalisation de la peau qui ne se trouvent pas dans les préparations de gels.

Delinted cottonseed in diets for finishing sheep.

The use of agricultural by-products might provide an important alternative to improve animal agriculture and to reduce feeding costs. The effects of inclusion in the diet of four levels of delinted cottonseed (0, 80, 160, and 240 g/kg) on intake, digestibility, nitrogen balance, blood parameters, and the ingestive behaviour of confined sheep were studied. Twenty-four mixed-breed rams with an average body weight of 27.6 ± 2.9 kg were used in a completely randomised design with four treatments. The addition of delinted cottonseed (DCS) did not alter (P > 0.05) the intake of dry matter, crude protein, organic matter, neutral detergent fibre, or ether extract in the two forms calculated (g/day and % body weight). The use of different levels of DCS in sheep feed did not influence (P > 0.05) the voluntary water intake. The dietary DCS levels linearly affected (P < 0.05) the digestibility coefficients of the dry matter (DM), organic matter, neutral detergent fibre, ether extract, and non-fibrous carbohydrates. The DCS inclusion levels did not affect the nitrogen balance (P = 0.22), plasma concentrations of urea (P = 0.51), and glucose (P = 0.17).The feeding efficiency and rumination in g DM/h reduced linearly (P < 0.05) with the addition of DCS in the diet. Therefore, the addition of delinted cottonseed affects the intake, digestibility, and ingestive behaviour of confined sheep, and the addition of up to 80 g/kg delinted cottonseed in the diet of confined sheep is recommended.

Study of the Influence of Formulation Variables in Bioadhesive Emulgels Using Response Surface Methodology.

The aim of the present work was to study the main formulation variables that influence attributes of bioadhesive emulgels based on a combination of polymers, using response surface methodology (RSM). Bioadhesive products continue to gain attention in topical cutaneous administration as they allow long residence times on the application site, which is important when a long dermal action and a reduced product administration frequency are desired. A Box-Behnken design of experiments (DoE) was introduced to study the effect of formulation variables on quality attributes of the emulgels. The effects of concentration of carbomer interpolymer type A (Polym1), xanthan gum (Polym2) and mineral oil (Oil) on detachment force (Fdetch), spreadability (Spread), and phase separation by mechanical stress (PhSep) were investigated. RSM and desirability functions were applied for data analysis. Emulgels were further characterized by viscosity and extrudability measurements. Polym1 showed a positive effect on Fdetch, while the increase in concentrations of Polym2 and Oil decreased this property. Polym1 and Polym2 favored emulgel PhSep. However, their interaction effect decreased it. The combination of 0.4-0.6% of carbomer and 0.2-0.3% of gum was able to produce easy-to-spread bioadhesive emulgels with mineral oil as discontinuous phase in the presence of a low surfactant concentration. Based on the DoE results, value ranges for the variables, which could achieve for the experimental domain to get the critical quality attributes of emulgels jointly within the specification limits, were able to be identified using RSM supported by desirability functions.

Bioadhesive hydrogels for cosmetic applications.

INTRODUCTION: The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. OBJECT: The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. METHODS: Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol(®) 980) or kappa carrageenan potassium salt (Gelcarin(®) GP-812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen(™) TR-1), xanthan gum or guar gum). Hydrogels were characterized by means of physico-chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check-all-that-apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. RESULTS: Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. CONCLUSION: Physico-chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin.

Effect of dietary buriti oil on the quality, fatty acid profile and sensorial attributes of lamb meat.

Forty crossbred (Santa Ines × Dorper) male lambs were used to investigate the effect of dietary buriti oil (BOIL) intake on meat quality, fatty acid (FA) composition and sensory attributes. A completely randomized design with five BOIL intake levels (0, 12, 24, 36 and 48 g/kg DM) was used. Increasing dietary BOIL intake linearly reduced the DMI, slaughter weight, cooking loss, shear force, yellowness, 16:0, c9-18:1 FA concentrations, and the delta-9-desaturase activity index computed using c9-16:1 and 16:0 as product and substrate pair, cis-MUFA and Æ©MUFA/Æ©SFA ratio of lamb meat (P ≤ 0.05); however, increasing dietary BOIL intake quadratically increased the energy intake, lipid content and linearly increased the total FA intake, chroma, collagen, total BI, 18:0, 20:3n-6 concentration and sensory attributes of lamb meat (P ≤ 0.05), without affecting health indexes regarding fat consumption. BOIL addition at levels above 24 g/kg DM in lamb diet reduces growth, however, improves tenderness, flavor and "goat" aroma intensity and slightly changes meat FA levels, promoting better acceptance by panelists.

The influence of the mechanical behaviour of the middle ear ligaments: a finite element analysis.

The interest in computer modelling of biomechanical systems, mainly by using the finite element method (FEM), has been increasing, in particular for analysis of the mechanical behaviour of the human ear. In this work, a finite element model of the middle ear was developed to study the dynamic structural response to harmonic vibrations for distinct sound pressure levels applied on the eardrum. The model includes different ligaments and muscle tendons with elastic and hyperelastic behaviour for these supportive structures. Additionally, the nonlinear behaviour of the ligaments and muscle tendons was investigated, as they are the connection between ossicles by contact formulation. Harmonic responses of the umbo and stapes footplate displacements, between 100 Hz and 10 kHz, were obtained and compared with previously published work. The stress state of ligaments (superior, lateral, and anterior of malleus and superior and posterior of incus) was analysed, with the focus on balance of the supportive structures of the middle ear, as ligaments make the link between the ossicular chain and the walls of the tympanic cavity. The results obtained in this work highlight the importance of using hyperelastic models to simulate the mechanical behaviour for the ligaments and tendons.

Finite element modelling of the surgical procedure for placement of a straight electrode array: Mechanical and clinical consequences.

A cochlear implant is an electronic device implanted into the cochlea to directly stimulate the auditory nerve. Such device is used in patients with severe-to-profound hearing loss. The cochlear implant surgery is safe, but involves some risks, such as infections, device malfunction or damage of the facial nerve and it can result on a poor hearing outcome, due to the destruction of any present residual hearing. Future improvements in cochlear implant surgery will necessarily involve the decrease of the intra-cochlear damage. Several implant related variables, such as materials, geometrical design, processor and surgical techniques can be optimized in order for the patients to partially recover their hearing capacities The straight electrode is a type of cochlear implant that many authors indicate as being the less traumatic. From the finite element analysis conducted in this work, the influence of the insertion speed, the friction coefficient between the cochlear wall and the electrode array, and several configurations of the cochlear implant tip were studied. The numerical simulations of the implantation showed the same pattern of the insertion force against insertion depth, thus indicating the different phases of the insertion. Results demonstrated that lower insertion speeds, friction coefficients and tip stiffness, led to a reduction on the contact pressures and insertion force. It is expected that these improved configurations will allow to preserve the residual hearing while reducing surgical complications.

Effect of mesh anchoring technique in uterine prolapse repair surgery: A finite element analysis.

The female pelvic cavity involves muscles, ligaments, endopelvic fasciae and multiple organs where different pathologies may occur, namely the pelvic organ prolapse (POP). The synthetic implants are used for the reconstructive surgery of POP, but severe complications associated with their use have been reported, mainly related to their mechanical properties (e.g., implant stiffness) and microstructure. In this study, we mimicked a transvaginal reconstructive surgery to repair the apical ligaments (uterosacral ligaments (USLs) and cardinal ligaments (CLs)), by modeling, their impairment (90% and 50%) and/or total rupture. The implants to reinforce/replace these ligaments were built based on literature specifications and their mechanical properties were obtained through uniaxial tensile tests. The main aim of this study was to simulate the effect of mesh anchoring technique (simple stich and continuous stitch), and compare the displacement magnitude of the pelvic tissues, during Valsalva maneuver. The absence/presence of the synthetic implant was simulated when total rupture of the CLs and USLs occurs, causing a variation of the vaginal displacement (9% for the CLs and 27% for the USLs). Additionally, the simulations showed that there was a variation of the supero-inferior displacement of the vaginal wall between different anchoring techniques (simple stich and continuous stitch) being approximately of 10% for the simulation USLs and CLs implant. The computational simulation was able to mimic the biomechanical behavior of the USLs and CLs, in response to different anchoring techniques, which can be help improving the outcomes of the prolapse surgery.

Mechanical Effects of a Maylard Scar During a Vaginal Birth After a Previous Caesarean.

Caesarean section is one of the most common surgeries worldwide, even though there is no evidence supporting maternal and perinatal long-term benefits. Furthermore, the mechanical behavior of a caesarean scar during a vaginal birth after caesarean (VBAC) is not well understood since there are several questions regarding the uterine wound healing process. The aim of this study is to investigate the biomechanical Maylard fiber reorientation and stiffness influence during a VBAC through computational methods. A biomechanical model comprising a fetus and a uterus was developed, and a chemical-mechanical constitutive model that triggers uterine contractions was used, where some of the parameters were adjusted to account for the matrix and fiber stiffness increase in the caesarean scar. Several mechanical simulations were performed to analyze different scar fibers arrangements, considering different values for the respective matrix and fibers stiffness. The results revealed that a random fiber arrangement in the Maylard scar has a much higher impact on its mechanical behavior during a VBAC than the common fibers arrangement present in the uninjured uterine tissue. An increase of the matrix scar stiffness exhibits a lower impact, while an increase of the fiber's stiffness has no significant influence.

Effects of dietary energy content and source using by-products on carcass and meat quality traits of cull ewes.

In cull ewes, energy supply by time short periods can affect growth, carcass traits, and meat quality. The objective of this study was to evaluate the effect of biscuit bran (BB) and cashew nut bran (CNB) in diets with different total digestible nutrient (TDN) content on animal performance and carcass and meat traits of cull ewes. Twenty Morada Nova cull ewes, with the initial BW of 30.1 ±â€¯3.56 kg, and three years of age were distributed in a completely randomized design into factorial scheme 2 × 2, with two energy sources (BB and CNB) × two levels of TDN. All diets were isoproteic with variations in TDN content increased by 10% (TDN10) and 25% (TDN25) above the recommended requirement for the study category, which was 66.0% TDN. The experimental period lasted 56 days, in which daily intake in relation to metabolic weight and weight performance of the animals was determined. The hot carcass, the cold carcass, commercial cuts, loin eye area, and subcutaneous fat thickness were measured, obtained, or calculated. A sample of the Longissimus lumborum (LL) muscle was used by determination of physical-chemical composition, sensory, and fatty acid (FA) profile analysis. The ANOVA was performed to access the effect of diet and energy level on the characteristics studied, and means were compared by the Turkey and Kruskal Wallis tests at 5% of probability. A higher daily gain weight was observed from TDN25 (P = 0.006). Among by-products, higher nutrient intakes were observed in animals fed with BB diets (P < 0.01), except for crude protein. The same patterns have been observed for live weight, reconstituted half-carcass, higher yield in fat thickness, and internal carcass length. Cashew nut bran produced darker colored meat (P = 0.017) and higher cooking weight loss (P = 0.008). Higher lipid content was observed in animals submitted to diets with CNB and TDN25 (P = 0.001). The internal length of the carcass was higher in animals fed with BB (P = 0.041). All diets did not effect on sensory characteristics (P > 0.05). Total digestible nutrient in 25% above recommended promotes higher weight gain and meat with higher lipid content and less weight loss by cooling. The inclusion of BB, compared to CNB, provides a higher weight of carcasses and better conformation, in addition to lower total lipid content with higher proportion for monounsaturated FAs in meat, providing more attractive features for the consumer market.

Characteristics, Origins, and Biosignature Preservation Potential of Carbonate-Bearing Rocks Within and Outside of Jezero Crater.

Carbonate minerals have been detected in Jezero crater, an ancient lake basin that is the landing site of the Mars 2020 Perseverance rover, and within the regional olivine-bearing (ROB) unit in the Nili Fossae region surrounding this crater. It has been suggested that some carbonates in the margin fractured unit, a rock unit within Jezero crater, formed in a fluviolacustrine environment, which would be conducive to preservation of biosignatures from paleolake-inhabiting lifeforms. Here, we show that carbonate-bearing rocks within and outside of Jezero crater have the same range of visible-to-near-infrared carbonate absorption strengths, carbonate absorption band positions, thermal inertias, and morphologies. Thicknesses of exposed carbonate-bearing rock cross-sections in Jezero crater are ∼75-90 m thicker than typical ROB unit cross-sections in the Nili Fossae region, but have similar thicknesses to ROB unit exposures in Libya Montes. These similarities in carbonate properties within and outside of Jezero crater is consistent with a shared origin for all of the carbonates in the Nili Fossae region. Carbonate absorption minima positions indicate that both Mg- and more Fe-rich carbonates are present in the Nili Fossae region, consistent with the expected products of olivine carbonation. These estimated carbonate chemistries are similar to those in martian meteorites and the Comanche carbonates investigated by the Spirit rover in Columbia Hills. Our results indicate that hydrothermal alteration is the most likely formation mechanism for non-deltaic carbonates within and outside of Jezero crater.

Investigating the birth-related caudal maternal pelvic floor muscle injury: The consequences of low cycle fatigue damage.

BACKGROUND: One of the major causes of pelvic organ prolapse is pelvic muscle injury sustained during a vaginal delivery. The most common site of this injury is where the pubovisceral muscle takes origin from the pubic bone. We hypothesized that it is possible for low-cycle material fatigue to occur at the origin of the pubovisceral muscle under the large repetitive loads associated with pushing during the second stage of a difficult labor. PURPOSE: The main goal was to test if the origin of the pubovisceral muscle accumulates material damage under sub-maximal cyclic tensile loading and identify any microscopic evidence of such damage. METHODS: Twenty origins of the ishiococcygeous muscle (homologous to the pubovisceral muscle in women) were dissected from female sheep pelvises. Four specimens were stretched to failure to characterize the failure properties of the specimens. Thirteen specimens were then subjected to relaxation and subsequent fatigue tests, while three specimens remained as untested controls. Histology was performed to check for microscopic damage accumulation. RESULTS: The fatigue stress-time curves showed continuous stress softening, a sign of material damage accumulation. Histology confirmed the presence of accumulated microdamage in the form of kinked muscle fibers and muscle fiber disruption in the areas with higher deformation, namely in the muscle near the musculotendinous junction. CONCLUSIONS: The origin of ovine ishiococcygeous muscle can accumulate damage under sub-maximal repetitive loading. The damage appears in the muscle near the musculotendinous junction and was sufficient to negatively affect the macroscopic mechanical properties of the specimens.

Altered mechanics of vaginal smooth muscle cells due to the lysyl oxidase-like1 knockout.

The remodeling mechanisms that cause connective tissue of the vaginal wall, consisting mostly of smooth muscle, to weaken after vaginal delivery are not fully understood. Abnormal remodeling after delivery can contribute to development of pelvic organ prolapse and other pelvic floor disorders. The present study used vaginal smooth muscle cells (vSMCs) isolated from knockout mice lacking the expression of the lysyl oxidase-like1 (LOXL1) enzyme, a well-characterized animal model for pelvic organ prolapse. We tested if vaginal smooth muscle cells from LOXL1 knockout mice have altered mechanics including stiffness and surface adhesion. Using atomic force microscopy, we performed nanoindentations on both isolated and confluent cells to evaluate the effect of LOXL1 knockout on in vitro cultures of vSMCs cells from nulliparous mice. The results show that LOXL1 knockout vSMCs have increased stiffness in pre-confluent but decreased stiffness in confluent cultures (p* < 0.05) and significant decreased surface adhesion in pre-confluent cultures (p* < 0.05). This study provides evidence that the weakening of vaginal connective tissue in the absense of LOXL1 changes the mechanical properties of the vSMCs. STATEMENT OF SIGNIFICANCE: Pelvic organ prolapse is a common condition affecting millions of women worldwide, which significantly impacts their quality of life. Alterations in vaginal and pelvic floor mechanical properties can change their ability to support the pelvic organs. This study provides evidence of altered stiffness of vaginal smooth muscle cells from mice resembling pelvic organ prolapse. The results from this study set a foundation to develop pathophysiology-driven therapies focused on the interplay between smooth muscle mechanics and extracellular matrix remodeling.

Minimally invasive transforaminal and anterior lumbar interbody fusion surgery at level L5-S1.

This paper presents a finite element analysis to investigate the biomechanical changes caused by transforaminal (TLIF) and anterior lumbar interbody fusion (ALIF) at the L5-S1 level, applying two different implants: T_PAL (TLIF) and SynFix (ALIF). The main objective is to determine which one is more stable for patients. Numerical simulations of segmental motion show that, in the early postoperative phase, displacements and rotation angles obtained in ALIF are greater than the corresponding ones obtained in TLIF, as well as the principal stress values on the ligaments. So, TLIF performed with T_PAL is more stable than ALIF, especially during the recovery phase.

Numerical simulation of lateral and transforaminal lumbar interbody fusion, two minimally invasive surgical approaches.

The present study aims to compare spinal stability after two different minimally invasive techniques, the lateral lumbar interbody fusion (LLIF) and the transforaminal lumbar interbody fusion (TLIF) approaches. Two nonlinear three-dimensional finite element (FE) models of the L4-L5 functional spinal unit (FSU) were subjected to the loads that usually act on the lumbar spine. Findings show that the LLIF approach yields better results for torsion load case, due to the larger surface area of the implant. For extension, flexion and lateral bending loads, the TLIF approach presents smaller displacements probably due to the anterior placement of the cage and to the smaller damaged area of the annulus fibrosus.

Long-term AAV vector gene and protein expression in mouse brain from a small pan-cellular promoter is similar to neural cell promoters.

The neurogenetic, lysosomal enzyme (LSE) deficiency diseases are characterized by storage lesions throughout the brain; therefore, gene transfer needs to provide widespread distribution of the normal enzyme. Adeno-associated virus (AAV) vectors can be effective in the brain despite limited transduction because LSEs are exported to neighboring cells (cross-correction) to reverse the metabolic deficit. The extent of correction is determined by a combination of the total amount of LSE produced by a vector and the spatial distribution of the vector within the brain. Neuron-specific promoters have been used in the brain because AAV predominantly transduces neurons. However, these promoters are large, using up a substantial amount of the limited cloning capacity of AAV vector genomes. A small promoter that is active in all cells, from the LSE beta-glucuronidase (GUSB), has been used for long-term expression in AAV vectors in the brain but the natural promoter is expressed at very low levels. The amount of LSE exported from a cell is proportional to the level of transcription, thus more active promoters would export more LSE for cross-correction, but direct comparisons have not been reported. In this study, we show that in long-term experiments (>6 months) the GUSB minimal promoter (hGBp) expresses the hGUSB enzyme in brain at similar levels as the neuron-specific enolase promoter or the promoter from the latency-associated transcript of herpes simplex virus. The hGBp minimal promoter thus may be useful for long-term expression in the central nervous system of large cDNAs, bicitronic transcription units, self-complimentary or other designs with size constraints in the AAV vector system.

Simulation of the uterine contractions and foetus expulsion using a chemo-mechanical constitutive model.

During vaginal delivery women sustain stretching of their pelvic floor, risking tissue injury and adverse outcomes. Since studies in pregnant women are limited with ethical constraints, computational models have become an interesting alternative to elucidate the pregnancy mechanisms. This research investigates the uterine contractions during foetus expulsion without an imposed trajectory. Such physical process is captured by means of a chemo-mechanical constitutive model, where the uterine contractions are triggered by chemical stimuli. The foetus descent, which includes both pushing and resting stages, has a descent rate within the physiological range. Moreover, the behaviour of the foetus and the uterus stretch agree well with clinical data presented in the literature. The follow-up of this study will be to obtain a complete childbirth simulation, considering also the pelvic floor muscles and its supporting structures. The simulation of a realistic rate of descent, including the pushing and resting stages, is of significant importance to study the pelvic floor muscles due to their viscoelastic nature.

The effect of physiotherapy on fatigue and physical functioning in chronic fatigue syndrome patients: A systematic review.

OBJECTIVE: The objectives of this work were to fill the gap in the scientific literature and to evaluate the results of physical therapy treatments in individuals affected by chronic fatigue syndrome, considering only studies that employed a randomized controlled trial. METHODS: A systematic review was carried out according to PRISMA guidelines. Three bibliographic databases were searched: MEDLINE, Cochrane Library, and PEDro. The minimum prerequisites for papers to be included in the systematic review were that they had to (a) employ a randomized controlled trial; (b) be published in English; and (c) be published during the last ten years (2007-2017). The studies were evaluated according to Jadad score. RESULTS: Four studies were included. This systematic review suggests that a treatment that is more effective than all the others cannot be defined. This conclusion is related to the low number of investigated studies; therefore, the collected results cannot be generalized. CONCLUSION: Chronic fatigue syndrome is not yet a well-understood pathology, and the physical mechanisms that influence the outcomes still need more study. Rehabilitation programs that promote physiotherapy techniques such as exercise, mobilization, and body awareness (e.g., MRT and GET) are the most effective in reducing medium and long-term fatigue severity in CFS patients.