Rapid nongenomic estrogen signaling controls alcohol drinking behavior.

The sex steroid hormone estrogen is a key modulator of numerous physiological processes and adaptive behaviors, but it may also be co-opted to drive maladaptive behaviors. While many behavioral roles for estrogen signaling have been shown to occur through canonical genomic signaling mechanisms via nuclear receptors, estrogen can also act in a neurotransmitter-like fashion at membrane-associated estrogen receptors to rapidly regulate neuronal function. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high circulating estrogen but a causal role for estrogen in alcohol drinking has not been established. Here, we demonstrate that gonadally intact female mice consume more alcohol and display an anxiolytic phenotype when they have elevated levels of ovarian-derived estrogen across the estrous cycle. We found that rapid, nongenomic estrogen signaling at membrane-associated estrogen receptor alpha in the bed nucleus of the stria terminalis (BNST) is necessary and sufficient for the pro-alcohol drinking effects of ovarian estrogen signaling, regardless of the transcriptional program of a high ovarian estrogen state. We further show that a population of corticotropin-releasing factor (CRF) BNST neurons (BNSTCRF) is a critical mediator of these effects, as high estrogen rapidly enhances synaptic excitation of BNSTCRF neurons and promotes their role in driving binge alcohol drinking. These findings show a causal role for endogenous, ovarian-derived estrogen in hormonal modulation of risky alcohol consumption and provide the first demonstration of a purely rapid, nongenomic signaling mechanism of ovarian estrogen in the brain controlling behavior in gonadally intact females.

A vascularized 3D model of the human pancreatic islet forex vivostudy of immune cell-islet interaction.

Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively byßcells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of isletßcells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlyingßcell damage in diabetes rely onin vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing-key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel,ex vivoplatform for studying human islet biology in both health and disease.

Cytological diagnosis of genital ureaplasma urealyticum and its importance in cervical inflammation.

OBJECTIVE: Cervical smear cytology, which is a gynecological cervical cancer screening test, can provide information about the presence of pathogenic microorganisms or the inflammation they cause. Among them, Ureaplasma urealyticum (Uu), which is a subspecies of Mycoplasma was held responsible for high-grade cervical intraepithelial lesions and malignancy due to long-lasting complicated vulvovaginitis clinic. We aimed at investigating the role of Uu in the inflammatory process of the cervix and to describe the cytological features that enable it to be recognized microscopically in cervical smear test. PATIENTS AND METHODS: Cervical smear and mycoplasma culture data of 123 women with complicated vulvovaginitis findings were evaluated. According to the Uu culture results, women were divided into two groups: the Uu-positive (n=59) and the Uu-negative group (n=64). The groups were compared in terms of cervical smear results, macroscopic view of the cervix, and secondary cytological evaluation results. RESULTS: The presence of inflammatory signs (83.1%) in the Uu-positive group was observed to be 83.1%, whereas 67.2% in the Uu-negative group, and the difference between the two groups was found to be significant (p=0.04). Besides, the difference in aggregated polymorphonuclear leukocytes (PMNL) between Uu-positive group (59.3%) and Uu-negative group (40.6%) was statistically significant (p=0.04). Similarly, nuclear atypia of epithelial cells in the Uu-positive group (33.9%) was observed to be higher than in the Uu-negative group (17.2%) (p=0.03). CONCLUSIONS: Uu causes inflammation of the cervix and cervical intraepithelial lesions. Aggregated PMNL observed in cervical smear cytology may be one of the findings that will give clues for Uu.

The effect of growth hormone addition protocols to poor ovarian responders in in vitro fertilization cycles.

OBJECTIVE: In vitro fertilization failure (IVF) is high in women with poor ovarian response or non-responder. For this reason, the addition of adjuvant treatments to IVF protocols has come to the fore. We assessed to investigate the effects of adjuvant GH therapy initiated in the mid-luteal phase on IVF success in poor ovarian response or non-responder women. PATIENTS AND METHODS: A retrospective study was performed in 93 poor ovarian response or non-responder women from a single center. GH treatment was added (GH-plus group) in the mid-luteal phase of the previous menstrual cycle to 47 of the women who underwent controlled ovarian stimulation with the flexible antagonist protocol. 46 women, as another group, were applied to a flexible antagonist-only protocol (GH-free group). The IVF outcome results were evaluated and compared within the groups. RESULTS: The number of retrieved oocytes was statistically significantly higher in the GH-plus group (2.28±1.975) than in the GH-free group (1.24±1.728) (p=0.01). Although statistically insignificant (p=0.55), the clinical pregnancy rate was higher in the GH-plus group [(8/47), 17%] than in the GH-free group [(5/46, 11%]. The cancellation rate was statistically significantly higher in the GH-free group (65.2%) than in the GH-plus group (44.7%) (p=0.04). No oocyte retrieved cycle rate was higher in the GH-free group (56%) than in the GH-plus group (25%) (p=0.002). CONCLUSIONS: Adjuvant GH therapy administration to IVF protocol in the mid-luteal phase gives poor ovarian response or non-responder women a chance to have a baby.

Human in vitro vascularized micro-organ and micro-tumor models are reproducible organ-on-a-chip platforms for studies of anticancer drugs.

Angiogenesis is a complex process that is required for development and tissue regeneration and it may be affected by many pathological conditions. Chemicals and drugs can impact formation and maintenance of the vascular networks; these effects may be both desirable (e.g., anti-cancer drugs) or unwanted (e.g., side effects of drugs). A number of in vivo and in vitro models exist for studies of angiogenesis and endothelial cell function, including organ-on-a-chip microphysiological systems. An arrayed organ-on-a-chip platform on a 96-well plate footprint that incorporates perfused microvessels, with and without tumors, was recently developed and it was shown that survival of the surrounding tissue was dependent on delivery of nutrients through the vessels. Here we describe a technology transfer of this complex microphysiological model between laboratories and demonstrate that reproducibility and robustness of these tissue chip-enabled experiments depend primarily on the source of the endothelial cells. The model was highly reproducible between laboratories and was used to demonstrate the advantages of the perfusable vascular networks for drug safety evaluation. As a proof-of-concept, we tested Fluorouracil (1-1,000 µM), Vincristine (1-1,000 nM), and Sorafenib (0.1-100 µM), in the perfusable and non-perfusable micro-organs, and in a colon cancer-containing micro-tumor model. Tissue chip experiments were compared to the traditional monolayer cultures of endothelial or tumor cells. These studies showed that human in vitro vascularized micro-organ and micro-tumor models are reproducible organ-on-a-chip platforms for studies of anticancer drugs. The data from the 3D models confirmed advantages of the physiological environment as compared to 2D cell cultures. We demonstrated how these models can be translated into practice by verifying that the endothelial cell source and passage are critical elements for establishing a perfusable model.

Multi-omic molecular comparison of primary versus metastatic pancreatic tumours.

BACKGROUND: Molecular profiling is increasingly used to match patients with metastatic cancer to targeted therapies, but obtaining a high-quality biopsy specimen from metastatic sites can be difficult. METHODS: Patient samples were received by Perthera to coordinate genomic, proteomic and/or phosphoproteomic testing, using a specimen from either the primary tumour or a metastatic site. The relative frequencies were compared across specimen sites to assess the potential limitations of using a primary tumour sample for clinical decision support. RESULTS: No significant differences were identified at the gene or pathway level when comparing genomic alterations between primary and metastatic lesions. Site-specific trends towards enrichment of MYC amplification in liver lesions, STK11 mutations in lung lesions and ATM and ARID2 mutations in abdominal lesions were seen, but were not statistically significant after false-discovery rate correction. Comparative analyses of proteomic results revealed significantly elevated expression of ERCC1 and TOP1 in metastatic lesions. CONCLUSIONS: Tumour tissue limitations remain a barrier to precision oncology efforts, and these real-world data suggest that performing molecular testing on a primary tumour specimen could be considered in patients with pancreatic adenocarcinoma who do not have adequate tissue readily available from a metastatic site.

Hyperbaric oxygen therapy for iatrogenic arterial gas embolism after CT-guided lung biopsy : A case report.

Iatrogenic arterial gas embolism (AGE) can be life-threatening. The only causal treatment is immediate hyperbaric oxygen therapy (HBOT). This article reports on a case of a 74-year-old male patient who underwent computed tomography (CT)-guided lung biopsy of suspect nodules after squamous cell carcinoma of the tonsils. During puncture, sudden cardiovascular arrest occurred. The CT scan documented severe arterial gas embolism in the aorta, spinal canal, left heart ventricle, and brain. The patient was then transferred to our hospital for HBOT. After the first HBOT, an additional CT scan showed regression of all gas inclusions. In the treatment of gas embolism, HBOT is considered the gold standard and is indispensable. It is primarily used to reduce acute bubble effects and to avoid secondary bubble effects. Unfortunately, the long persisting gas occlusions and perfusion deficits led to severe hypoxic brain damage and a poor prognosis for the patient. In this case report we present the management of (iatrogenic) arterial gas embolism and point out the necessity of immediate HBOT. Furthermore, we discuss the pathophysiology leading to arterial gas embolism on the basis of the gas laws.

A virtual molecular tumor board to improve efficiency and scalability of delivering precision oncology to physicians and their patients.

OBJECTIVES: Scalable informatics solutions that provide molecularly tailored treatment recommendations to clinicians are needed to streamline precision oncology in care settings. MATERIALS AND METHODS: We developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations. RESULTS: The VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly 2-fold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support. DISCUSSION: VMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand. CONCLUSION: Further development of such clinical augmentation tools that systematically combine patient-derived molecular data, real-world evidence from electronic health records and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.

Evaluation of Different Decellularization Protocols on the Generation of Pancreas-Derived Hydrogels.

Different approaches have investigated the effects of different extracellular matrices (ECMs) and three-dimensional (3D) culture on islet function, showing encouraging results. Ideally, the proper scaffold should mimic the biochemical composition of the native tissue as it drives numerous signaling pathways involved in tissue homeostasis and functionality. Tissue-derived decellularized biomaterials can preserve the ECM composition of the native tissue making it an ideal scaffold for 3D tissue engineering applications. However, the decellularization process may affect the retention of specific components, and the choice of a proper detergent is fundamental in preserving the native ECM composition. In this study, we evaluated the effect of different decellularization protocols on the mechanical properties and biochemical composition of pancreatic ECM (pECM) hydrogels. Fresh porcine pancreas tissue was harvested, cut into small pieces, rinsed in water, and treated with two different detergents (sodium dodecyl sulfate [SDS] or Triton X-100) for 1 day followed by 3 days in water. Effective decellularization was confirmed by PicoGreen assay, Hoescht, and H&E staining, showing no differences among groups. Use of a protease inhibitor (PI) was also evaluated. Effective decellularization was confirmed by PicoGreen assay and hematoxylin and eosin (H&E) staining, showing no differences among groups. Triton-treated samples were able to form a firm hydrogel under appropriate conditions, while the use of SDS had detrimental effects on the gelation properties of the hydrogels. ECM biochemical composition was characterized both in the fresh porcine pancreas and all decellularized pECM hydrogels by quantitative mass spectrometry analysis. Fibrillar collagen was the major ECM component in all groups, with all generated hydrogels having a higher amount compared with fresh pancreas. This effect was more pronounced in the SDS-treated hydrogels when compared with the Triton groups, showing very little retention of other ECM molecules. Conversely, basement membrane and matricellular proteins were better retained when the tissue was pretreated with a PI and decellularized in Triton X-100, making the hydrogel more similar to the native tissue. In conclusion, we showed that all the protocols evaluated in the study showed effective tissue decellularization, but only when the tissue was pretreated with a PI and decellularized in Triton detergent, the biochemical composition of the hydrogel was closer to the native tissue ECM. Impact Statement The article compares different methodologies for the generation of a pancreas-derived hydrogel for tissue engineering applications. The biochemical characterization of the newly generated hydrogel shows that the material retains all the extracellular molecules of the native tissue and is capable of sustaining functionality of the encapsulated beta-cells.

Consensus guidelines for the use and interpretation of angiogenesis assays.

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative.

Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRB-approved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices. 23 of these patients also underwent traditional tumor tissue-based NGS testing. cfDNA was not detected in 9/34 (26%) patients. Overall concordance between blood and tumor tissue NGS assays was low, with only 25% sensitivity of blood-based NGS for tumor tissue NGS. Mutations in KRAS, the major PDA oncogene, were only detected in 10/34 (29%) blood samples, compared to 20/23 (87%) tumor tissue biopsies. The presence of mutations in circulating DNA was associated with reduced overall survival (54% in mutation-positive versus 90% in mutation-negative). Our results suggest that in the setting of previously treated, advanced PDA, liquid biopsies are not yet an adequate substitute for tissue biopsies. Further refinement in defining the optimal patient population and timing of blood sampling may improve the value of a blood-based test.

Strongly baryon-dominated disk galaxies at the peak of galaxy formation ten billion years ago.

In the cold dark matter cosmology, the baryonic components of galaxies-stars and gas-are thought to be mixed with and embedded in non-baryonic and non-relativistic dark matter, which dominates the total mass of the galaxy and its dark-matter halo. In the local (low-redshift) Universe, the mass of dark matter within a galactic disk increases with disk radius, becoming appreciable and then dominant in the outer, baryonic regions of the disks of star-forming galaxies. This results in rotation velocities of the visible matter within the disk that are constant or increasing with disk radius-a hallmark of the dark-matter model. Comparisons between the dynamical mass, inferred from these velocities in rotational equilibrium, and the sum of the stellar and cold-gas mass at the peak epoch of galaxy formation ten billion years ago, inferred from ancillary data, suggest high baryon fractions in the inner, star-forming regions of the disks. Although this implied baryon fraction may be larger than in the local Universe, the systematic uncertainties (owing to the chosen stellar initial-mass function and the calibration of gas masses) render such comparisons inconclusive in terms of the mass of dark matter. Here we report rotation curves (showing rotation velocity as a function of disk radius) for the outer disks of six massive star-forming galaxies, and find that the rotation velocities are not constant, but decrease with radius. We propose that this trend arises because of a combination of two main factors: first, a large fraction of the massive high-redshift galaxy population was strongly baryon-dominated, with dark matter playing a smaller part than in the local Universe; and second, the large velocity dispersion in high-redshift disks introduces a substantial pressure term that leads to a decrease in rotation velocity with increasing radius. The effect of both factors appears to increase with redshift. Qualitatively, the observations suggest that baryons in the early (high-redshift) Universe efficiently condensed at the centres of dark-matter haloes when gas fractions were high and dark matter was less concentrated.

Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

[Autologous Skin Cell Transplantation and Medical Needling for Repigmentation of Depigmented Burn Scars on UV-protected and UV-exposed Skin]. / Autologe Hautzelltransplantation und Medical Needling zur Repigmentierung von depigmentierten Verbrennungsnarben an UV-exponierter und -geschützter Haut.

Background: Burn scars remain a serious physical and psychological problem for the affected people. Both clinical studies and basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient related to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling does not influence repigmentation of large hypopigmented scars. Objective: The goal is to evaluate whether both established methods - needling (improvement of scar quality) and non-cultured autologous skin cell suspension (NCASCS) "ReNovaCell" (repigmentation) - can be combined. So far, 20 patients with mean age of 33 years (6-60 years) with deep second and third degree burn scars have been treated. The average treated tissue surface was 94 cm² (15-250 cm²) and was focused on areas like face, neck, chest and arm. Methods: Medical needling is performed using a roller covered with 3 mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, NCASCS is applied, according to the known protocol. The patients have been followed up for 15 months postoperatively. The scars were subdivided into "UV-exposed" and "UV-protected" to discover whether the improved repigmentation is due to transfer of melanocytes or to reactivation of existing melanocytes after exposure to UV or the sun. Results: The objective measures show improved pigmentation in both UV-exposed and UV-protected groups. Melanin increases 1 year after NCASCS treatment in the UV-protected group are statistically significant. Conclusion: Medical needling in combination with NCASCS shows promise for repigmentation of burn scars, even in sun protected scars.

Combination of medical needling and non-cultured autologous skin cell transplantation (ReNovaCell) for repigmentation of hypopigmented burn scars.

Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with mean age of 33 years (6-60 years) with scars from deep second and third degree burns have been treated. The average treated surface area was 94cm2 (15-250cm2) and was focused on prominent areas such as the face, neck, chest and arm. Percutaneous collagen induction or "medical needling" was performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (NCASCS) was produced and applied using the ReNovaCell Autologous Cell Harvesting Device (Avita Medical), according to the manufacturer's instructions. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, as well as with patient and observer ratings. Patient satisfaction/preference was also obtained. Taken together, the pigmentation ratings and objective measures indicate individual improvement in 17 of the study participants. The melanin increases seen 12 months after NCASCS treatment are statistically significant. Medical needling in combination with NCASCS shows promise for repigmentation of burn cars.

Effects of partial replacement of corn and alfalfa silage with tall fescue hay on total-tract digestibility and lactation performance in dairy cows.

Our objective was to evaluate the effects of replacing either corn or alfalfa silage with tall fescue hay on total-tract neutral detergent fiber (NDF) digestibility and lactation performance in dairy cows. Twenty-four primiparous (75±35 d in milk) and 40 multiparous (68±19 d in milk) Holstein cows were blocked by parity and randomly assigned to 1 of 4 treatment groups in a pen equipped with 32 feeding gates to record intake by cow. Each gate was randomly assigned to 1 treatment group; thus, each cow had access to all 8 gates within the respective treatment and cow was the experimental unit. Treatments were formulated to replace either corn silage (CS) or alfalfa silage (AS) with tall fescue hay (TF) as follows (DM basis): 33% AS and 67% CS (control; 33AS67CS), 60% TF and 40% AS (60TF40AS), 60% TF and 40% CS (60TF40CS), and 33% TF and 67% CS (33TF67CS). The experiment was a 7-wk continuous lactation trial with a 2-wk covariate period. Milk production did not differ among treatments and averaged 40.4 kg/d. Fat yield and concentration and protein yield and concentration did not differ among treatments and averaged 1.58 kg/d, 3.94%, 1.28 kg/d, and 3.15%, respectively. Dry matter intake was greater for 33AS67CS (24.5 kg/d) compared with 60TF40CS (22.1 kg/d) and 33TF67CS (22.7 kg/d), and tended to be greater than 60TF40AS (23.2 kg/d). In vivo total-tract dry matter digestibility did not differ among treatments and averaged 66.2%. In vivo total-tract NDF digestibility was lower for 33AS67CS (37.8%) compared with 60TF40AS (44.4%) and 33TF67CS (45.3%), and similar to 60TF40CS (42.4%). In vivo total-tract NDF digestibility and an estimate of in situ total-tract NDF digestibility were similar between techniques across all treatment diets (42.3 vs. 42.6%, respectively). Inclusion of tall fescue grass hay increased the total-tract NDF digestibility of the diet and has the potential to replace corn silage and alfalfa silage and maintain milk production if economically feasible based on current market prices.

The effects of calcium hydroxide-treated whole-plant and fractionated corn silage on intake, digestion, and lactation performance in dairy cows.

The objective of this trial was to evaluate, in dairy cattle, the effects of calcium hydroxide treatment of whole-plant corn and a treatment applied to the bottom stalk fraction of the corn plant, achieved by harvesting corn in 2 crop streams. The treatments were calcium hydroxide-treated corn silage (TRTCS), toplage supplemented with calcium hydroxide-treated stalklage (TPL), a positive control of brown midrib corn silage (BMR), and a negative control of conventional whole-plant corn silage (WPCS). The toplage was harvested at a height of 82 cm with 2 of the 6 rows set as ear-snapping to incorporate higher tissues into the stalklage. Stalklage was harvested at 12 cm, and other corn silages were harvested at 27 cm. Sixteen pens, each with 8 Holstein cows averaging 70±25 d in milk and 46±11 kg of milk d(-1), were assigned 4 per treatment in a completely randomized design. The diet was approximately 40% corn silage, 20% alfalfa silage, and 40% concentrate on a dry matter basis. A 2-wk covariate period with conventional corn silage was followed by an 8-wk treatment period in which the 4 corn silage treatments were the only effective difference in diets. Cows fed TPL and TRTCS consumed more (1.9 and 1.4 kg of organic matter d(-1), respectively) than did cows fed WPCS. Milk yield was greater for cows fed BMR, TPL, and TRTCS. Cows fed BMR and TPL produced 2.9 and 2.7 kg d(-1), respectively, more energy-corrected milk (ECM) than cows fed WPCS, and cows fed TRTCS had the greatest ECM production (4.8 kg of ECM d(-1) greater than cows fed WPCS). No differences in body weight or body condition scored were observed. Milk fat concentration was similar among treatments and milk protein concentration was reduced for TRTCS. Starch and neutral detergent fiber digestibility were greater for cows fed TRTCS.

Comparison of in situ versus in vitro methods of fiber digestion at 120 and 288 hours to quantify the indigestible neutral detergent fiber fraction of corn silage samples.

Ruminal digestion of neutral detergent fiber (NDF) is affected in part by the proportion of NDF that is indigestible (iNDF), and the rate at which the potentially digestible NDF (pdNDF) is digested. Indigestible NDF in forages is commonly determined as the NDF residue remaining after long-term in situ or in vitro incubations. Rate of pdNDF digestion can be determined by measuring the degradation of NDF in ruminal in vitro or in situ incubations at multiple time points, and fitting the change in residual pdNDF by time with log-transformed linear first order or nonlinear mathematical treatments. The estimate of indigestible fiber is important because it sets the pool size of potentially digestible fiber, which in turn affects the estimate of the proportion of potentially digestible fiber remaining in the time series analysis. Our objective was to compare estimates of iNDF based on in vitro (IV) and in situ (IS) measurements at 2 fermentation end points (120 and 288h). Further objectives were to compare the subsequent rate, lag, and estimated total-tract NDF digestibility (TTNDFD) when iNDF from each method was used with a 7 time point in vitro incubation of NDF to model fiber digestion. Thirteen corn silage samples were dried and ground through a 1-mm screen in a Wiley mill. A 2×2 factorial trial was conducted to determine the effect of time of incubation and method of iNDF analysis on iNDF concentration; the 2 factors were method of iNDF analysis (IS vs. IV) and incubation time (120 vs. 288h). Four sample replicates were used, and approximately 0.5g/sample was weighed into each Ankom F 0285 bag (Ankom Technology, Macedon, NY; pore size=25 µm) for all techniques. The IV-120 had a higher estimate of iNDF (37.8% of NDF) than IS-120 (32.1% of NDF), IV-288 (31.2% of NDF), or IS-288 technique (25.7% of NDF). Each of the estimates of iNDF was then used to calculate the rate of degradation of pdNDF from a 7 time point in vitro incubation. When the IV-120 NDF residue was used, the subsequent rates of pdNDF digestion were fastest (2.8% h(-1)) but the estimate of lag was longest (10.3h), compared with when iNDF was based on the IS-120 or IV-288 NDF residues (rates of 2.3%h(-1) and 2.4%h(-1); lag times of 9.7 and 9.8 h, respectively). Rate of pdNDF degradation was slowest (2.1% h(-1)) when IS-288 NDF residue was used as the estimate of iNDF. The estimate of lag based on IS-288 (9.4h) was similar to lag estimates calculated when IS-120 or IV-288 were used as the estimate of iNDF. The TTNDFD estimates did not differ between treatments (35.5%), however, because differences in estimated pools of iNDF resulted in subsequent changes in rates and lag times of fiber digestion that tended to cancel out. Estimates of fiber digestion kinetic parameters and TTNDFD were similar when fit to either the linear or nonlinear fiber degradation models. All techniques also yielded estimates of iNDF that were higher than predicted iNDF based on the commonly used ratio of 2.4 × lignin.

Combination of medical needling and non-cultured autologous skin cell transplantation (renovacell) for repigmentation of hypopigmented burn scars in children and young people.

Burn scars remain a serious physical and psychological problem for the affected. Clinical studies as well as basic scientific research have shown that Medical Needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, Medical Needling has no influence on repigmentation of large hypopigmented scars. The goal is to evaluate whether both established methods - Needling (improvement of scar quality) and ReNovaCell (repigmentation) - can be combined. So far, eight patients with mean age of 20 years (6-28 years) with deep second and third degree burn scars have been treated. The average treated tissue surface was 76cm² (15-250cm²) and was focused on areas like face, neck, chest and arm. Medical Needling is performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (ReNovaCell) is applied, according to the known protocol. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, and with patient and observer ratings. Patient satisfaction/preference was also obtained. We present the final study results. Taken together, pigmentation ratings and objective measures indicate improvement in six of the study participants. Melanin increase seen 12 months after ReNovaCell treatment in the study group as a whole is notable. Medical Needling in combination with ReNovaCell shows promise for repigmentation of burn scars.

Les séquelles de brûlures demeurent un problème physique et psychologique pour les victimes. Les études cliniques, ainsi que les recherches scientifiques ont montré que l'Aiguilletage médical peut améliorer de façon significative la qualité des cicatrices de brûlures avec un risque faible et un retentissement psychologique mineur chez les patients et ceci vis-à-vis de l'élasticité cutanée, l'hydratation, l'érythème et la déperdition hydrique trans épidermique. Cependant l'Aiguilletage médical n'a pas d'influence sur la repigmentation des vastes cicatrices hypo pigmentées. Le but est d'apprécier la possible association des deux méthodes: Aiguilletage (amélioration de la cicatrice) et ReNovaCell (re pigmentation). Ainsi 8 patients avec une moyenne d'age de 20 ans (6-28 ans) présentant des cicatrices de brûlures du 2e degré profond et 3e degré ont été traités. La moyenne de surface traitée était de 76cms carrés (15-20cms carrés) et les zones choisies furent la face, le cou, le thorax et les bras. L'Aiguilletage médical était réalisé avec un rouleau couvert d'aiguilles de 3mm de long. Le rouleau est manié verticalement, horizontalement et en diagonale sur la cicatrice provoquant un microtraumatisme. Puis, les cellules cutanées autologues non cultivées en suspension (ReNovaCell) sont appliquées suivant le protocole connu. Les patients furent suivis pendant 12 mois après le traitement. Les changements de pigmentation étaient mesurés de façon objective par le patient et évalués suivant une grille. La satisfaction du patient et son avis étaient alors notés. Nous présentons les résultats de la fin de notre étude. Prenant en compte les taux de repigmentation et les mesures objectives, l'amélioration fut constatée chez 6 de nos patients. L'augmentation de la mélanine fut observée 12 mois après le traitement par ReNovaCell dans l'ensemble du groupe de façon notable. L'association « Aiguilletage médical +ReNovaCell ¼ est riche de promesse pour la repigmentation des cicatrices de brûlures.