Treatment Research Articles

A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer.

Alofanib is a small-molecule allosteric extracellular FGFR2 inhibitor. We report safety and preliminary efficacy from the first-in-human phase 1b study of alofanib in heavily pretreated patients with advanced gastric cancer. The standard dose-escalation design 3+3 aimed to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Alofanib was administered daily intravenously 5 days on, 2 days off. There were five dose levels (50-350 mg/m2). All patients received alofanib until disease progression or unacceptable toxicity. 21 patients were enrolled. Patients were predominantly male (71%), 67% had 2 and more metastatic sites, including liver metastases (43%), 19% had ECOG PS 2, and were heavily pretreated (86% had previous 2 and more treatment lines). During dose escalation, no dose-limiting toxicities were observed, and MTD was not defined. 15 (71.4%) patients had at least one adverse event associated with the treatment (TRAE). Grade 3 or higher TRAEs were observed in 6 patients (28.6%). The most common TRAEs included reactions immediately after administration, diarrhea, thrombocytopenia, arthralgia, and headache. The median progression-free survival and overall survival was 3.63 (95% CI 1.58-5.68) and 7.0 (95% CI 3.82-10.18) months, respectively. The 6- and 12-month overall survival rates were 57.1% and 33.3%. Disease control rate was 68% with one durable partial response. The MTD has not been reached and dose of 350 mg/m2, 5 days on, 2 days off has been declared as RP2D. Alofanib showed acceptable tolerability and preliminary signs of clinical activity in the late-line treatment of metastatic gastric cancer. (ClinicalTrials.gov identifier: NCT04071184).

Associations of Eliminating Free-Stall Head Lock-Up during Transition Period with Milk Yield, Health, and Reproductive Performance in Multiparous Dairy Cows: A Case Report

The objective of this retrospective case study was to understand the effects of eliminating free-stall lock-up time during 21 days postpartum on milk yield, reproductive performance, and health events at a large dairy herd. A group of 200 cows were selected as the treatment (TRT) group, which did not receive a lock-up time during early lactation, and a separate group of 200 cows served as the control (CON) group, which received on average 2 h/day of lockup time. The TRT group had greater milk yield (mean ± SE) on the third monthly milk test day (33.1 ± 0.75 vs. 29.9 ± 1.22; p = 0.04) and tended to have greater milk yield on the second test day (38.3 ± 1.55 vs. 39.1 ± 0.79; p = 0.06) compared to the CON cows. Milk fat% (mean ± SE) was greater in the TRT group than in the CON group on the first monthly milk test (3.65 ± 0.06 vs. 3.31 ± 0.12, p = 0.01). The TRT group had lower linear somatic cell scores on the first monthly milk test day compared to the CON group (2.6 ± 0.24 vs. 3.2 ± 0.11; p = 0.01). Cows in the TRT group had lower days in milk at first breeding (DIMFB) (66.2 ± 3.7 vs. 76.7 ± 2.9; p = 0.02) and were confirmed pregnant earlier as indicated by smaller days in milk to pregnancy (DIMPREG) (96.9 ± 12.32 vs. 112.1 ± 5.5; p < 0.01). Cows in the TRT group also had fewer incidences of all health events combined (13% vs. 30.5%; p < 0.001), lameness (3% vs. 9.5%; p = 0.01), and mastitis (3% vs. 16%; p < 0.001). We conclude that eliminating the stall lockup may have contributed to the increased milk yield, health, and reproductive performance of dairy cows in this dairy herd. Future prospective cohort studies are needed to further assess the potential effect of eliminating lock up time on cow performance.

Onconephrology: acute kidney disease after preventive ileostomy in a patient with colorectal cancer

The risk of acute kidney injury (AKI) in cancer patients is much higher than in the general population. Common causes of AKI in this group of patients are toxicity of chemotherapy com ponents and water-electrolyte imbalances. The risks of AKI increase significantly if the patient has a history of chronic kidney disease of any etiology. Risk assessment and correction, prevention and treatment of acute and chronic renal dysfunction are the standard tasks of onconephrology The clinical case of acute kidney disease described here illustrates the main mechanisms and factors of organ dysfunction and its outcomes as a con­ sequence of colorectal cancer treatment. The necessity of multidisciplinary cooperation in determining the management and treatm ent tactics of such patients is shown, that is essential for the long-term prognosis.

Effects of timing of grouping and split-weaning on growth performance and behaviour of piglets in a multi-suckling system

Variation in body weight (BW) of piglets at weaning is a drawback for successful implementation of multi-suckling (MS) systems. The current study investigated the combination of two intervention strategies, i.e. the timing of grouping and split-weaning, aiming to improve the BW gain of low birthweight piglets in an MS system and thereby reduce the BW variation at weaning on day 48 postpartum (p.p.). Eight batches of 5 sows with their litters were divided into 4 control (CTRL) and 4 treatment (TREAT) batches. In each litter, the second lowest (LBW) and highest (HBW) birthweight piglets from both sexes were selected as focal piglets. CTRL piglets were grouped on day 8 p.p. and no split-weaning was applied; TREAT piglets were grouped on day 13 p.p. and the three heaviest non-focal piglets per litter were split-weaned on day 35 p.p. Behaviour and feed intake were measured in focal piglets, and BW and mortality were measured in all piglets. Results showed that: (1) Throughout lactation there were no differences in BW or BW gain between CTRL and TREAT, nor were birthweight × treatment interactions found. (2) After grouping, there were no obvious differences between CTRL and TREAT in feeding and suckling behaviours on day 18, damage scores on snout, ear or tail and skin lesions on day 27, nor were birthweight × treatment interactions found. (3) After split-weaning, in week 6, piglets in TREAT tended to consume less feed than CTRL (P = 0.072). Low birthweight piglets in TREAT consumed numerically less feed and spent numerically less time contacting feed during the day than CTRL piglets. In week 6, there was a significant birthweight × treatment interaction in dry matter milk intake (P = 0.030), caused by a higher milk intake of TREAT-LBW piglets compared with CTRL-LBW piglets. In week 6, TREAT piglets tended to be present more at front and middle teats (P = 0.052) and tended to have lower snout damage scores (P = 0.084) than CTRL piglets. (4) Piglet crushing of all piglets in TREAT tended to be higher during the period when TREAT piglets were not yet grouped i.e. during days 9–14 than CTRL (P = 0.087). To conclude, split-weaning of the heavy piglets increased milk intake particularly of low birthweight piglets but this did not lead to a reduction in BW variation at weaning, as the increased milk intake was largely compensated for by a simultaneous decrease in feed intake.

Feeding a Saccharomyces cerevisiae fermentation product before and during a feed restriction challenge on milk production, plasma biomarkers, and immune function in Holstein cows.

Periods of decreased feed intake may disrupt function of the intestinal barrier. Feeding NutriTek® (NTK; Diamond V, Cedar Rapids, IA), a postbiotic from S. cerevisiae fermentation (SCFP), improved health and supported anti-inflammatory functions. We investigated the effects of feeding NTK to cows before and during a period of feed restriction (FR) designed to model periods of intestinal barrier dysfunction. In total, 16 multiparous cows (97.1 ± 7.6 DIM; n = 8/group) were fed a control diet (CON) or CON plus 19 g/d NTK for 9 wk (Phase 1; P1) and then were subjected to an FR challenge for 5 d, during which they were fed 40% of their ad libitum intake from the 7 d prior to FR. Milk yield (MY) and DMI were collected daily. During FR, milk was collected daily for composition, blood daily to measure plasma biomarkers and to measure monocyte and neutrophil phagocytosis and oxidative burst on d 1, 3, and 5. Data were analyzed using a mixed model in SAS 9.4. All data were subjected to repeated measures ANOVA. Dietary treatment (TRT), Day, and their interaction (TRT × Day) were considered as fixed effects and cow as the random effect. For analysis of P1, data collected during a 7-d adaptation phase were used as a covariate. During P1, NTK cows tended to have greater DMI and had greater fat, ECM and FCM yields, and feed efficiency (ECM/DMI and FCM/DMI). Protein yield tended to be greater in NTK compared with CON cows. A tendency for greater monocyte phagocytosis was detected with NTK. However, during FR, feeding NTK led to lower MY and lactose yield and tended to lower solids percentage. While NTK cows tended to have reduced neutrophil oxidative burst than CON cows during FR (NTK: 26.20%, CON: 36.93%), there was no difference in phagocytosis (NTK: 7.92%, CON: 6.31%). Plasma biomarkers of energy metabolism, liver function, inflammation, and oxidative stress during the FR period did not differ. Overall, results suggested that feeding NTK increased the yield of FCM, ECM, feed efficiency and milk components prior to FR.

Возможности повторного использования дождевых сточных вод

The problems of the efficiency of the implementation of sustainable development Programs in terms of the conservation of water resources in urbanized areas are aimed at finding alternative solutions with the inclusion of innovative technologies and the search for optimal criteria for controlling water use conditions. It should be noted that there is insufficient knowledge and elaboration of technologies for the use of rain water resources. The purpose of the research is to develop and supplement the standardized requirements governing the possibility of reusing rainwater with the justification of the criteria for choosing systems for their collection and treatment. There are discrepancies and methodically insufficient elaboration of the problem of substantiating the criteria for choosing rain water collection and treatment systems, taking into account current trends in technology development, it is necessary to add standardized requirements regulating the mechanism of their reuse. To solve the problem, it is proposed to conduct studies clarifying the qualitative composition of surface wastewater, for which laboratory sampling of rainwater from various catchment surfaces was carried out. The results of chemical analyses showed a difference in the characteristics of rainwater collected from roofs, roads and courtyards. Based on the qualitative composition of rainwater, it was found that rainwater collected from roofs has the least pollution. Technological features of rainwater collection and treatme nt for their further reuse are described. It is proposed to create an accumulating reservoir, the replenishment of which will be carried out as it is used, taking into account the calculated values of the basic techniques. A technological scheme for the treatment of rainwater collected from roofs has been developed, the simplicity and cheapness of the proposed technology is noted.

Transcriptomic analysis reveals the molecular mechanisms underlying osteoclast differentiation in the estrogen-deficient pullets

Several previous reports have suggested that estrogen (E2) is a vital signal responsible for the regulation of skeletal homeostasis and bone remodeling in mammals. E2 could efficiently accelerate the growth of medullary bone in pullets during sexual maturity. Furthermore, the low E2 level can strengthen the mechanical bone functions in female hens. However, mechanistic studies to describe the effects of E2 on bone in pullets during the initiation of the puberty period are remaining elusive. Therefore, the aim of this study was to explore the effect of inhibiting E2 biosynthesis on the biomechanical properties and its molecular mechanism during sexual maturity of pullets. In this study, a total of 90 Hy-line Sonia pullets with comparable body weight at 13 wk of age were selected and categorized into 2 separate groups. Daily, 0.5 mg/4 mL of letrozole (LZ) was orally administered to the treatment (TRT) group and 4 mL of saline to the control (CON) group of pullets for 6 wk. Compared with the CON group, a lower plasma E2 level was observed in the TRT group. Furthermore, plasma P, Gla protein (BGP), and 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) levels were markedly suppressed, whereas the plasma alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels were significantly elevated. Moreover, the cortical bone thickness and breaking strength of the tibia and femur, the bone mineral density of the humerus, and the bone mineral content of the humerus as well as the femur were increased significantly. The expression levels of 340 differentially expressed genes (DEGs) differed significantly between the CON and TRT group in the tibia at 19 wk of age. Among them, 32 genes were up-regulated, whereas 308 were down-regulated in the TRT group. The variations in candidate genes associated with osteoclast differentiation and cell adhesion may indicate that LZ inhibits E2 biosynthesis, consequently, reduces osteoclast differentiation by suppressing inter-cellular communication and cells attaching to extracellular matrix components. Taken together, the present study demonstrated that inhibiting E2 synthesis during sexual maturity of pullets decreased osteoclast differentiation and considerably enhanced bone quality.

Trea tment of polypoid choroidal vasculopathy complicated by extensive subretinal hemorrhage. A case report

Polypoid choroidal vasculopathy (PCV) is a type of wet form of age-related macular degeneration (AMD). It is characterized by formation aneurysmal dilations of abnormal choroidal vessels (polyps) under the retinal pigment epithelium (RPE) in the choroid. The disease leads to a vision loss due to formation of serous retinal detachment, neuroepithelium detachment and RPE, subretinal hemorrhages, fibrosis, atrophy of RPE. The generally accepted treatment of PCV is antiangiogenic therapy.The purpose of this work is to present and to analyze the clinical case of polypoid choroidal vasculopathy treatment complicated by extensive subretinal hemorrhage.Description of the case. This clinical case of PCV in the right eye that is complicated by extensive subretinal hemorrhage on the background of antiangiogenic therapy in a 72-year-old man is presented. In addition to standard ophthalmological research methods, we performed optical coherence tomography (OCT) with Cirrus HD-OCT 5000 Zeiss (Carl Zeiss, Germany), angio-OCT with Optovue Solix High-Speed Spectral Optical Coherence Tomograph (Optovue, USA) and fundus photo registration with Topcon TRC-NW8F Retinal Camera (Topcon, Japan). The comprehensive surgical approach was applied to this patient, including posterior subtotal vitrectomy with our Stellaris PC microsurgical system (Baush&Lomb, USA) and the prourokinase subretinal injection against the background of aflibercept antiangiogenic therapy and removal of a concomitant cataract with implantation of an intraocular lens (IOL).Discussion. The early treatment of this patient and at the right time procedure of microinvasive 25-G vitrectomy combined with prourokinase subretinal injection contributed to the resorption of hemorrhage in the shortest possible time and improved visual functions from 0.02 to 0.6.Conclusions. The presented comprehensive approach of PCV treatment and its complications made possible to provide social rehabilitation of the patient and to preserve high values of visual functions in the affected eye.

CATALASE ACTIVITY IN INTERACTION WITH IONIZED WATER AND OTHER ANTIOXIDANTS IN BLOOD PLASMA, LIVER, AND KIDNEY OF THE RAT DURING HYPERTHERMIC STRESS

The similarity between the responses seen after heat stress and those happening in the condition of oxidative stress suggests that heat stress is an environmental element that stimulates the generation of reactive oxygen species (ROS). Alkaline water, also known as ionized or reduced water (ERW), is water that has undergone electrochemical activation and has a pH greater than 7. The ERW also has excellent redox properties and other reducing features. ERW mimics the activity of the antioxidant enzyme, such as catalase (CAT) by scavenging ROS. The aim of this study was to examine the catalase activity in interaction with ERW under hyperthermic stress by including non-enzymatic antioxidants, glutathione, and vitamin C. White laboratory Young female Wistar rats weighing 180–220 g were divided into three groups of 15 for the experiment. Oxidative stress was caused by 41°C acute hyperthermic exposure. The first group is referred to as the control group (CPM), the second group is referred to as the ionized water treatment (TAM), and the third group is referred to as the ionized water treatment with added glutathione and vitamin C (TAD). The treatment period lasted 21 days. The treatment applied respectively to each group during the period of hyperthermic exposure caused a significant difference in CAT activity in blood plasma among the three groups. Liver CAT activity was increased in all three groups. Treatment for 21 days in all three groups led to a decrease in CAT activity in the blood plasma and in the kidneys. Acute hyperthermic exposure on the 21st day in the CPM and TAD groups for blood plasma has a statistically significant difference (p < 0.01). Also, in both the TAM and TAD groups there is a statistically significant difference (p < 0.01) in CAT activity, which is in contrast to the difference in the liver and kidney CAT activity between the remaining compared groups, which was shown to be statistically insignificant.

Treated tannery effluent and its impact on the receiving stream water: physicochemical characterization and cytogenotoxic evaluation using the Allium cepa test.

Tanneries are considered some of the most polluting industries due to the heavy use of toxic compounds, most of which are released into water bodies, thus exerting adverse effects on aquatic biota. However, the effects on organisms of treated effluents when released into the natural environment are rarely evaluated. This study aims to assess the physicochemical parameters of a tannery effluent after treatment (TE) at a Common Effluent Treatment Plant as well as the water of the receiving stream and to evaluate cytogenotoxic effects in Allium cepa. Three sampling sites (A: TE discharge point; B: 100m downstream from site A along the receiving stream; C: 100m upstream from site A along the stream) were selected. Onion bulbs were exposed to TE (100%, 80%, 60% v/v), water samples from sites B and C, and tap water for 72h. Chromosomal aberration and mitotic index were analyzed on the root cells of A. cepa. The TE was above the standard limits for ammoniacal nitrogen, COD, and total nitrogen. No cytogenotoxicity was observed in A. cepa exposed to samples from sites A and C. However, the stream water sampled downstream from the TE discharge site significantly reduced the mitotic index, indicating a cytotoxic effect. Therefore, this demonstrates the effects of interactions between the receiving water and the complex chemical mixtures in the TE. The findings thus showed that the toxicity assessment of treated effluents along with the receiving water body would provide valuable and more realistic information about the joint toxicity of chemical pollutants in aquatic environments.

Direct Resin Composite Restoration in Anterior Tooth: 10 Years of Clinical Follow-Up

The emergence and development of resin-based materials, such as resin composites and adhesive systems, have shifted the restorative treatment of anterior teeth with caries lesions and/or fractures. Thus, based on the disadvantages of indirect restorations, direct esthetic restorations are restorative options even for anterior teeth with exten sive loss of hard tissues. This study aimed to describe and discuss the direct resin composite restoration performed to solve the esthetic and functional impairments of the upper anterior teeth with diastemas. The upper left central incisor received total crown preparation for indirect restoration. Clinical results after 10 years were recorded. Considering the clinical characteris tics of dental restorations, it is possible to conclude that direct resin composite restorations reestablished the esthetic and functional properties satisfactorily, even in a tooth with extensive coronal destruction. The success of the restorative treatm ent was dependent on factors related to the materials´ properties, oral habits of the patient, and mostly the clinical skills of th e dental clinician.

Nourishing neonatal piglets with synthetic milk and Lactobacillus sp. at birth highly modifies the gut microbial communities at the post-weaning stage.

The importance of probiotics in pig production is widely recognized. However, the precise role of probiotics in regulating the gut microbiota of piglets has not been assessed extensively. Therefore, we intend to examine whether suckling pigs ingesting with synthetic milk (SM) and probiotics along with mother milk has a carryover effect on its growth and gut health at the post-weaning stage. A total of 40 [Duroc× (Yorkshire× Landrace)] neonates with an initial BW of 1.49 ± 0.28 kg were assigned to one of two treatments groups: control (CON) and treatment (TRT). Control group piglets were nourished with synthetic milk, while TRT group piglets were nourished SM with (1 × 109 CFU/g) Lactobacillus sp. probiotics. The treatment group piglets showed higher (p < 0.05) body weight and daily gain at week 3 than the CON group piglets. 16S metagenome sequencing showed average demultiplexed reads and denoised reads counts of 157,399 and 74,945, respectively. The total ASV taxonomy number classified with a confidence threshold > 70% (default) on sequence alignment with the SILVA v138 reference database was 4,474. During week 1, Escherichia-Shigella, Clostridium sensu stricto 1, and Bacteroides were confirmed as the major dominant bacterial genera in both the groups at the genus level. However, during week 2, the relative proportion of Escherichia-Shigella, Clostridium sensu stricto 1, and Proteobacteria was decreased, while that of Lactobacillus and Bacteroidota was increased in pigs receiving the probiotic supplement. During weeks 2 and 3, Firmicutes, Proteobacteria, and Bacteroidota phyla were dominant in both groups. During week 6, the relative proportion of Proteobacteria was slightly increased in both groups. Furthermore, Prevotella was confirmed as the major dominant bacterial genus in both groups during weeks 3 and 6. This study suggests that nourishing neonatal piglets with synthetic milk and Lactobacillus sp. probiotics from birth to 21 days would be beneficial to enhance the gut health of piglets and to overcome post-weaning mortality.

Pemanfaatan Kopi Arabika (Coffea arabica) dalam Pembuatan Minuman Yoghurt sebagai Pangan Fungsional

The increase in the number of consumers of coffee drinks encourages variations in fermented beverage products that use coffee as an additive, one of which is yogurt. The addition of Arabica coffee which contains polyphenols are thought to stimulate growth and increase the activity of lactic acid bacteria. The purpose of this study was to determine the right concentration in the manufacture of Arabica coffee yogurt so as to produce good characteristics and fit into the yogurt standard SNI 01 - 2981 - 2009 and can increase the growth acti vity of lactic acid bacteria. The research method used was the descriptive experimental method with two replications and 4 treatments of added coffee concentration variations (0%, 1%, 2%, and 3%). The addition of 1% Arabica coffee to yogurt was the best tr eatment with the characteristics of total titratable acidity of 1.10% and total lactic acid bacteria of 8.94 Log CFU/g which has met the requirements of SNI 01 - 2981 - 2009, pH 4.15, and total polyphenols of 1.54 mgGAE/100 mL.

Effects of microbial inoculum on microbial community and enzyme activity involved in nitrogen-sulfur metabolism during sewage sludge composting

The purpose of this study was to access the effects of thermotolerant nitrifying microorganisms and sulfur-oxidizing bacteria on microbial community and enzyme activity involved in nitrogen‑sulfur metabolism during laboratory-scale sewage sludge (SS) composting，and to do a microbial-environmental factor association analysis to promote composting key species for nitrogen‑sulfur transformation in the body. The microbial community structure and the activities variation of six key enzyme involved were detected. The microbial inocula added had little impact on the diversity of the microbial community but changed its succession direction, and the abundance of Actinobacteria was decreased obviously of inoculation treatment (TR). The three dominant genera and indicator species in TR were significantly correlated with the conversion of nitrogen and sulfur. The addition of microbial inocula promoted the conversion of nitrogen and sulfur in SS compost, and increased the activities of the key enzymes and the microbial genera involved in nitrogen‑sulfur conversion. In other words, the nitrification and sulfur oxidation were enhanced simultaneously in the later stage of composting in TR.

A preliminary evaluation on mixed probiotics as an antimicrobial spraying agent in growing pig barn

The purpose of this study is to examine whether spraying an anti-microbial agent into the slurry pit will reduce the noxious odor substances from piggery barns. For this, a total of 200 crossbred ([Landrace × Yorkshire] × Duroc) growing pigs with an initial average body weight (BW) of 23.58 ± 1.47 kg were selected and housed in two different rooms, i.e. control (CON) and treatment (TRT). Each room has 100 pigs (60 gilts and 40 borrows). For a period of 42 days, all pigs were fed with corn-soybean meal-based basal diet. Later the noxious odor substances were measured by the following methods. First, fecal samples were randomly collected and stored in sealed and unsealed containers, and sprayed with the non-anti-microbial agent (NAMA) (saline water) and multi-bacterial spraying (MBS) agent (200 :1, mixing ratio-fecal sample : probiotic), Second, the slurry pit of CON and TRT rooms were directly sprayed with NAMA and MBS, respectively. The fecal sample that was stored in sealed and un-sealed containers and sprayed with MBS significantly reduced NH3 and CO2 concentration at the end of day 7. However, at the end of day 42, the fecal sample showed a lower H2S, methyl mercaptans, acetic acid, and CO2 concentration compared to the unsealed container. Moreover, at the end of days 7, 14, 21, 28, 35, and 42 compared to the CON room and TRT room slurry pit emits lower concentrations of NH3, acetic acid, H2S, and methyl mercaptans, and CO2 into the atmosphere. Based on the current findings, we infer that spraying anti-microbial agents on pig dung would be one of the better approaches to suppress the odor emission from the barn in the future.

Effect of substructural inhomogeneity on the anisotropy of physical and mechanical properties of textured materials

Today, anisotropy of the physical and mechanical properties of textured materials is mainly calculated based on average properties of a single crystal and information about the volume percent of grains that have different orientations, which can be determined with the help of distribution function. It is a fact that, in addition to the crystallographic texture, substructural inhomogeneity develops in rolled materials, which manifests itself as a difference in the distortion of the crystalline lattice (hardening) and elastic microstrains in grains belonging to different texture components. Substructural characterization is based on the X-ray method of Generalized Direct Pole Figures, which implies that a full profile of X-ray reflections is registered for different positions of the specimen, i.e. as a direct pole figure is being built. As a result, one can obtain the FWHMs of X-ray lines and elastic microstrains distributed on the stereographic projection. It means that a textured polycrystalline material that has undergone thermo-mechanical treatme nt is characterized with a certain spectrum of structural states and the presence of residual elastic microstrains. Therefore, the degree of macroscopic anisotropy of the product properties is defined both by the predominant grain orientation in the polycrystal and by the parameters of substructural inhomogeneity of grains belonging to different texture components. In spite of the fact that the elastic properties of an individual crystallite do not change and the tensile and compressive elastic microdeformations are balanced in the studied volume of the material, the elasticity of the whole system, i.e. of a polycrystal, changes due to interacting grains and the elastic energy stored in them. The authors propose a method for calculating elastic moduli and thermal expansion coefficients while accounting for the substructural inhomogeneity of the material by minimizing the elastic energy of the textured material. The efficiency of this method is demonstrated on specimens of a semi-finished channel pipe made of Zr &ndash; 2.5% Nb alloy.This research was funded by the Ministry of Science and Higher Education of the&nbsp;Russian Federation; Agreement No. 075-15-2021-1352.

Transcranial Electromagnetic Treatment Stops Alzheimer's Disease Cognitive Decline over a 2½-Year Period: A Pilot Study.

Background: There is currently no therapeutic that can stop or reverse the progressive memory impairment of Alzheimer’s disease (AD). However, we recently published that 2 months of daily, in-home transcranial electromagnetic treatment (TEMT) reversed the cognitive impairment in eight mild/moderate AD subjects. These cognitive enhancements were accompanied by predicted changes in AD markers within both the blood and cerebrospinal fluid (CSF). Methods: In view of these encouraging findings, the initial clinical study was extended twice to encompass a period of 2½ years. The present study reports on the resulting long-term safety, cognitive assessments, and AD marker evaluations from the five subjects who received long-term treatment. Results: TEMT administration was completely safe over the 2½-year period, with no deleterious side effects. In six cognitive/functional tasks (including the ADAS-cog13, Rey AVLT, MMSE, and ADL), no decline in any measure occurred over this 2½-year period. Long-term TEMT induced reductions in the CSF levels of C-reactive protein, p-tau217, Aβ1-40, and Aβ1-42 while modulating CSF oligomeric Aβ levels. In the plasma, long-term TEMT modulated/rebalanced levels of both p-tau217 and total tau. Conclusions: Although only a limited number of AD patients were involved in this study, the results suggest that TEMT can stop the cognitive decline of AD over a period of at least 2½ years and can do so with no safety issues.

Effect of DHA supplementation on broilers' growth performance, meat quality and blood profile.

Docosahexaenoic acid (DHA) is vital in the meat composition of broilers which is helpful to maintain a healthy diet in humans. The purpose of this study is to observe the effect of DHAfrom fish oil on growth performance, organ weight, and meat quality along with the blood profile of broilers. A total of 1600, 1-day old, Ross 308 broilers with an average body weight of 43.15 ± 1.35 g were used in 5 weeks trail. Birds were randomly allotted into one of four dietary treatment groups named: control (CON), basal diet; treatment (TRT)1, CON + 0.05% DHA; TRT2, CON + 0.1% DHA; TRT3, CON + 0.15% DHA. Each treatment group consisted of 20 replications with 20 broilers per pen. The experiment was divided into threephases. Phase 1 (Day 1-7), Phase 2 (Day 7-21), and overall phase (Day 21-35). During Phase 1 and 2, no significant changes were observed on body weight gain (BWG) as the DHA levels increased in the diet. However, during Phase 3, broilers fed diet supplemented with DHA at increasing levels linearly increased (p < 0.05) BWG and feed intake (FI). Also, water holding capacitywas reduced and drip loss percentage on Day 7 was increased linearly (p < 0.05) with the increase in DHA supplementation. At the end of trial, pH value of the meat was increased linearly (p < 0.05) with DHA levels. Moreover, blood cholesterol level, high-density lipoprotein, low-density lipoproteinwas significantly and linearly (p < 0.05) decreased in DHA supplemented groups. Broiler-fed diet with DHA supplement decreased the red blood celllinearly (p < 0.05) in blood. The results of the study indicate that DHA supplementation increased BWG with FI. Moreover, it has reduced blood lipid constituents with some adverse effect on meat quality.

Tanshinone IIA and Neural Stem Cell Combination Therapy Decreases Gut Inflammation and Maintains Gut Integrity in a Translational Pig Ischemic Stroke Model

ObjectivesImpaired gut homeostasis has been found in stroke, leading to leaky gut syndrome, increased levels of gut, brain, and systemic inflammation that further exacerbating brain damage. Tanshinone IIA (Tan IIA) and induced pluripotent stem cell derived neural stem cells (iNSCs) have been shown to decrease inflammation in the brain post-stroke resulting in reduced lesion volume and improved recovery response in rodent models. However, no group has evaluated the effect of Tan IIA and iNSCs brain treatments on intestinal changes. We evaluate the effects of Tan IIA and iNSCs delivered to the brain post-stroke on gut homeostasis in an ischemic stroke pig model.MethodsYucatan pigs (n = 12) underwent middle cerebral artery occlusion surgery and received either PBS (CON) or Tan IIA loaded PLGA nanoparticle (Tan IIA-NPs) and iNSCs treatment (TRT). PBS or Tan IIA-NPs were administered intracisternally at 1 hour post-stroke and PBS or iNSCs were transplanted into the perilesional region at 5 days post-stroke. Changes in fecal total SCFAs level were analyzed up to 12 weeks (wk) post-treatment (PT) and jejunum scrapings were collected at 12 wk PT for analysis.ResultsTRT had higher levels of total SCFAs than CON throughout the study period. Protein levels of jejunal TNF-α, TNFR1, and phosphorylation of Ikbα at 12 wk PT were lower in TRT compared to CON, suggesting that the treatment in brain decreased gut inflammation. The expression of jejunal Occludin, Claudin1, and ZO-1 was higher in TRT compared to CON. Moreover, protein levels of TNF-α and phosphorylation of Ikbα were negatively correlated with fecal total SCFAs levels at early stages of treatment (1–4 wk PT). Interestingly, total SCFA level at early treatment stages (up to 4 wk PT) was inversely related to hemorrhage volume measured by magnetic resonance imaging 1 day post-stroke, indicating a potential link between stroke severity and gut homeostasis.ConclusionsThe findings of the study indicate that local post-stroke brain treatment with Tan IIA and iNSCs decreases inflammation and membrane permeability through dynamic interplay with SCFAs in the gut. This study suggests further research on inflammation and SCFAs as key regulatory components and potential therapeutic targets that can modulate the gut brain axis to enhance stroke recovery in patients.Funding SourcesThis work was supported by the National Institutes of Health.

Cover Cropping Increases Soil Fungal-Bacterial Community Diversity and Network Complexity in Apple Orchards on the Loess Plateau, China

Soil microorganisms play a key role in soil fertility. Exploring the microbial community composition and diversity in response to cover crops is important for improving soil fertility in orchards. This study investigated how cover cropping can improve soil fertility by altering microbial community composition and the interrelations among soil microorganisms. Soil physicochemical and biological indicators and microbial community composition were evaluated after a 6-years application of cover cropping in an apple (Malus pumila cv. Fuji) orchard located on the Loess Plateau, China. Three treatments were applied: Trifolium repens treatment (TR), Lolium perenne treatment (LP), clear tillage treatment (CT). The soil of the cover crop treatments had a more complex microbial co-occurrence network than that of the clear tillage treatment; in particular, the correlations among fungi were significantly increased. Cover cropping increased the levels of soil organic matter (SOM), microbial biomass carbon (MBC), and total nitrogen (TN) in orchard soil. Changes in the fungal community were more related to microbial biomass nitrogen (MBN), TN, and carbon-nitrogen ratio (C:N). This indicates that cover cropping not only increases the diversity of soil microorganisms but also increases the interrelations between microbial groups, thereby improving the soil fertility of apple orchards on the Loess Plateau.