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The purpose of this study is that of comparing the effects of aquatic training to the effects of land training, to decrease the fat mass. 24 male students from the UPIT Physical Education and Sport Departament were subjects of the study. The subjects do not practice any performance sport except the loisir sport or the sport exercises from during the faculty hours. The same trainings and testing facilities and methods have been used for each evaluation and each lesson. Each training lasted for 45-70 minutes, 3 days per week. To establish fat mass, we used BIA (bioelectrical impedance analysis) principle. A significant difference of 2.72 has been registered (pre=18.2 and post=15.47) between the two groups with regards to the fat tissue established after the water training programs had ended.

It is a topic that has not been sufficiently researched, thus requiring investigations into the results, that can be had if we apply water-based exercises. In this sense, we conducted a study, during 10 weeks, which consisted in developing and experimenting with muscletraining programs in the aquatic environment and on land, as well as testing two strength indicators on a number of 24 students, aged 20-21 years, who were selected voluntarily and divided into 2 experimental groups in order to compare the results of the development of muscle strength of the upper body. The same training and testing facilities, methods, were used for each assessment and lesson. Each lesson lasted between 60 - 80 minutes, 3 days a week. The subjects improved in strength scores significantly, as compared to the control group, which followed the same muscular training protocol adapted for land, having a value comprised between: 1,25 and 7,98%.

People living with HIV live longer now due to highly active antiretroviral therapy. Due to their increased life expectancy, they have an increased cardiovascular risk cause by the traditional risk factors (smoking, use of ilicit drugs, obesity/lipodystrophy, dyslipidemia, diabetes, hypertension) and particular risk factors (endothelial dysfunction, inflammation, coagulation abnormalities, viral coinfections and antiretroviral therapy. The pathophysiology of accelerated atherosclerosis is complex. Coronary artery disease become an important cause of mortality in these patients. The incidence of coronary artery disease and especially of acute myocardial infarction is generally low among HIV patients, but it may by twice as high as in patients with the similar characteristics. Medical treatment for coronary disease in these patients has no special particularities comparing to general population, but possible drug interactions must be considered. Indication for coronary revascularization, either angioplasty, or aorto-coronary by-pass follows general indications for general population.

Vegetal diamine oxidase (vDAO), an enzyme proposed to relieve symptoms of histaminosis, shows better reactivity with histamine and aliphatic diamines, as well as higher enzymatic activity than DAO of animal origin. The objective of this study was to evaluate the enzyme activity of vDAO from germinating grains from Lathyrus sativus (grass pea) and Pisum sativum (pea), and to verify the presence of a neurotoxin, β-N-Oxalyl-L-α,β-diaminopropionic acid (β-ODAP), in the crude extract obtained from their seedlings. A targeted liquid chromatography–multiple-reaction monitoring mass spectrometry method was developed and used to quantify β-ODAP in the analysed extracts. An optimized sample preparation procedure, involving protein precipitation with acetonitrile followed by mixed-anion exchange solid-phase extraction, allowed for high sensitivity and good peak shape for β-ODAP detection. The Lathyrus sativus extract exhibited the highest vDAO enzyme activity of the extracts, followed by the extract from pea cultivar Amarillo from the Crop Development Centre (CDC). The results have also shown that even though β-ODAP was present in the crude extract from L. sativus, its content was far below the toxicity threshold (300 mg of β-ODAP/kg body/day). CDC Amarillo showed 5000-fold less β-ODAP than the undialysed L. sativus extract. It was concluded that both species can be considered as convenient sources of vDAO for potential therapeutic use.

The primary main aim of this article is to explore the changes and adjustments brought about by the COVID-19 pandemic to the therapeutic process in the transition from face-to-face talking therapy to online therapy. Online therapy sessions, once a niche, have now become the norm in therapeutic work. This, more than ever before, raises the question of the efficacy of online therapy compared to face-to-face talking therapy. A related question is how the “classical” elements of in-person therapies (especially the psychodynamic, affective and relational-based), such as: the therapeutic alliance, the therapeutic containing space, the therapeutic relationship, etc. work in the on-line setting. This article draws on a primary qualitative exploratory research carried among Romanian clients who undergo a psychodynamic type of therapy and who transitioned from face-to-face to online therapy as a reaction to the new constraints engendered by the COVID-19 pandemic and after the measures were relaxed, the transition from on-line to in-person therapy. Our focus is on how they experience online therapy compared to face-to-face therapy in terms of intimacy, therapeutic frame and efficacy, as well as on the boundaries challenged, erased and created by the switch between the two types of therapy settings.

The pandemic changed the paradigm of education at all levels. From primary schools to universities, teachers and students must conform to new patterns for teaching and learning. The goal of this paper is to share the experience resulted from the pilot project developed at the National Institute of Administration in order to deliver online training for public administration in the pandemic context. The project entitled PPP online (Romanian abbreviation for “online training programs”) was a challenge which supposed the redesign of the curricula and finding the best alternatives for delivering knowledge and interaction between trainers and participants. We must emphasize that there was only very limited experience in online training for Romanian public administration until 2020. In this paper we expose the choices considered for the transition to online training and the results of a study about participants’ perception regarding difficulties they encountered and the quality of programs. In this regard, we collected and analysed the feedback from more than 1000 participants (respondents to an online questionnaire). Our study has an optimistic conclusion about changing teaching and learning through technology in public administration. It can be appreciated that both trainers and participants can rapidly adapt to the conditions of the online learning environment and the proposed structure of training programs was validated by the results and positive feedback. We also present some best practices achieved during the pilot project.

Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative recipients develop anti-D antibodies (Abs). Subsequently, anti-D immunization further promotes the synthesis of Abs towards other blood group antigens in or outside the Rh system. The D antigen is also involved in 95% of cases of hemolytic disease of the newborn. Transfusions, hemotherapy, grafts, and obstetric history (abortions, ectopic pregnancy, births) are all risk factors for Rh isoimmunization. In the case of ABO compatibility between mother and fetus, Rh-positive fetal RBCs that have reached the maternal bloodstream are not destroyed by group agglutinins, and Rh antigenic sites are not hidden by the maternal immune system. But a Rh-negative mother with a homozygous Rh-positive husband will certainly have a Rh-positive fetus. As it has an irreversible evolution, the Rh isoimmunization once installed cannot be influenced in the sense of decreasing the Ab titer, therefore, injectable globulin has no effect. A particular case was that of a newborn with Rh system incompatibility associated with hereditary spherocytosis The clinical balance at birth reflects the severe jaundice of the female newborn of 3140 g, gestational age 38∕39 weeks, extracted by lower-segment transverse Caesarean section, with a double loop nuchal cord, Apgar score 8. Because the jaundice was severe and atypical (face and upper chest), we considered the possibility of coexistence of hemolytic disease of the newborn by Rh blood group incompatibility associated with hereditary spherocytosis, as it turned out to be true and mentioned. Changes in genes encoding proteins in the structure of the RBC membrane have amplified hemolysis induced by maternal-fetal isoimmunization in the Rh system. Massive hemolysis accentuated by congenital spherocytosis, confirmed later, imposed blood transfusion and dynamic monitoring.

Bos taurus × Bos indicus crosses are widespread in tropical and subtropical regions, nonetheless, quantitative information about the influence of B. indicus genetics on the reproductive performance of beef cattle is lacking. Herein, we determined the association between level of B. indicus genetics and reproduction from a 31-yr dataset comprising sequential breeding seasons of the University of Florida multibreed herd (n = 6,503 Angus × Brahman cows). The proportion of B. indicus genetics in this herd is evenly distributed by each 1/32nd or approximately 3-percentage points. From 1989 to 2020, the estrous cycle of cows was synchronized for artificial insemination (AI) based on detected estrus or timed-AI (TAI) using programs based on gonadotropin-releasing hormone and prostaglandin, and progestin/progesterone. All cows were exposed to natural service after AI and approximately 90-d breeding seasons, considering the day of AI as day 0. The proportion of B. indicus genetics of cows was associated negatively with pregnancy per AI, ranging from 51.6% for cows with 0%-19% of B. indicus genetics to 37.4% for cows with 81%-100% of B. indicus genetics. Similar association was found for estrous response at the end of the synchronization protocol, ranging from 66.3% to 38.4%, respectively. This reduced estrous response helped to explain the pregnancy results, once the pregnancy to AI of cows showing estrus was 2.3-fold greater than for those not showing estrus and submitted to TAI. Despite reduced pregnancy per AI, the increase in the proportion of B. indicus genetics of cows was not associated with a reduction in the proportion of pregnant cows at the end of the breeding season. Nevertheless, the interval from entering the breeding season to pregnancy was lengthened as the proportion of B. indicus genetics of cows increased. The median days to pregnancy was extended by 25 when the proportion of B. indicus genetics surpassed 78% compared with less than 20%. Thus, the increase in the proportion of B. indicus genetics of cows was related to a reduction in pregnancy per AI and lengthening the interval to attain pregnancy during the breeding season, but not with the final proportion of pregnant cows. As a result, reproductive management strategies directed specifically to cows with a greater proportion of B. indicus genetics are needed to improve the rate of pregnancy in beef herds.Cow–calf operations in the tropics and sub-tropics have benefited from the environmental adaptation provided by Bos indicus genetics. However, reproductive performance has been a cause of concern, although poorly quantified. This study characterized how much the B. indicus genetics in crossbred cows influence herd reproduction. We analyzed data from cows with known proportions of Angus and Brahman genetics, from the same crossbred herd, for 31 sequential breeding seasons. The increase in the proportion of B. indicus genetics reduced estrous response and pregnancy per artificial insemination after estrous synchronization, but not the proportion of pregnant cows at the end of the breeding season. Interval from the beginning of the breeding season to pregnancy was extended by 25 d when the proportion of B. indicus genetics surpassed 78%. In conclusion, reproductive management strategies directed specifically to cows with a greater proportion of B. indicus genetics are needed to improve the rate of pregnancy in beef herds.

Thermal stress limits beef cattle production and a shorter hair coat is a key thermoregulative adaptation that allows cattle to lose heat more efficiently. The objective of this study was to identify genetic variants associated with the length of the undercoat and topcoat of cattle utilizing 1456 Brangus heifers genotyped with the Bovine GGP F250 array. Seven SNPs in the PCCA gene were significantly associated with undercoat length. PCCA belongs to the biotin transport and metabolism pathway. Biotin deficiency has been reported to cause hair loss. Four SNPs in an 110 kb including a missense mutation in the PRLR gene were significantly associated with topcoat length. Whereas the association of this polymorphism with hair length is novel, the SLICK mutation in PRLR has previously been demonstrated to significantly impact hair length in cattle. These newly detected genetic variants may contribute to a shorter hair coat and more thermotolerant animals.

Oral papilloma lesions may appear as a result of HPV infection, or not, and only special molecular methods could differentiate them. Low-risk and high-risk HPV types could induce oral HPV papillomatosis with different natural evolution, clearance and persistence mechanisms. The pathogenic mechanisms are based on the crosstalk between the oral epithelial and immune cells and this very efficient virus. HPV acts as a direct inducer in the process of transforming a benign lesion into a malignant one, the cancerization process being also debated in this paper. According to the degree of malignity, three types of papillomatous lesions can be described in the oral cavity: benign lesions, potential malign disorders and malignant lesions. The precise molecular diagnostic is important to identify the presence of various virus types and also the virus products responsible for its oncogenicity. An accurate diagnostic of oral papilloma can be established through a good knowledge of etiological and epidemiological factors, clinical examination and laboratory tests. This review intends to update the pathogenic mechanisms driving the macroscopic and histological features of oral papillomatosis having HPV infection as the main etiological factor, focusing on its interreference in the local immunity. In the absence of an accurate molecular diagnostic and knowledge of local immunological conditions, the therapeutic strategy could be difficult to decide.

Brahman cattle are used for crossbreeding due to their maternal ability, heat, and parasite tolerance. Brahman displays delayed attainment of puberty compared with taurine breeds. The objective was to identify molecular markers in the blood of prepubertal heifers and bulls that predict early puberty attainment. We hypothesize that Brahmans that attains puberty have a blood metabolite signature that differs from animals that remain prepubertal. Plasma was collected 90 (-90d) and 30 (-30d) days prior to the beginning of the breeding season from 156 yearling Brahman heifers and 28 bulls. Animals were classified as pubertal (pub) or prepubertal (prepub) based on reproductive variables such as the reproductive tract score and pregnancy to insemination for heifers and scrotal circumference and semen quality for bulls. Plasma from 48 pub and 48 prepub heifers and 9 pub and 7 prepub bulls were submitted for quantitative mass spectrometry metabolomics analysis. There was a clear clustering of animals according to puberty status (orthogonal projections of latent structures discriminant analysis). Concentrations of the top three metabolites explaining clustering were analyzed by t-tests. As heifers approached maturity, there was a 3.03-, 11.76- and 2.08-fold change (P < 0.0001) in the concentrations of PC ae C42:3, ProBetaine, and PC ae C42:2 measured at -30 vs. -90 days. Similarly, for bulls, concentrations of HipAcid, C4 and SM (OH) C24:1 were 1.52-, 1.53-, and 1.45-fold greater (P < 0.0001), respectively. Comparing pub vs. prebub heifers on -90 d, there was a 1.26- (P < 0.001), 0.62- (P < 0.01) and 1.11-fold change (P < 0.05) for hArg, Putrescine and AABA concentrations, respectively. Regarding bulls on -90 d, there was a 1.57- (P < 0.01), 1.32- (P < 0.03) and 1.15-fold change (P < 0.03) for FA(18:1), FA(18:2) and DG(16:1_18:2) concentrations, respectively. In conclusion, we discovered potential markers for the prediction of puberty attainment based on plasma metabolomic signatures in Brahman.

The paper is dedicated to the experimental studies and numerical modeling of the airflow in a 3D cylindrical bifurcation. The computations are performed with the standard k – ε turbulence model implemented in the ANSYS Fluid Flow (Fluent) code of Workbench 2021R1. The direct visualizations and the numerical results are corroborated, with the aim to investigate the evolution of the vortical structures and the distribution of the flow rate in the bifurcation.

Introduction/Objective Germ cell tumor (GCT) is the most common cancer among males in the 20–39 year-old age range, representing 21% of invasive cancer diagnoses. Majority of bilateral testicular tumors are metachronous. The synchronous tumors comprise approximately 0.5%-1% of all cases. Most of the synchronous tumors share the same histologic pattern, predominantly seminoma. The synchronous bilateral testicular GCTs (SBTGCTs) with discordant subtypes are extremely rare. Methods/Case Report A 26-year-old male presented with left testicular pain, the ultrasound revealed bilateral testicular masses with calcifications and microlithiasis in the right side. His serum markers showed elevated alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG). Lactate dehydrogenase (LDH) was normal. He underwent bilateral orchiectomy. The pathology report showed a non-seminomatous mixed germ cell tumor, 2.0 cm in greatest dimension, predominantly embryonal carcinoma (90%), with a minor yolk sac tumor component (10%), lymphovascular invasion, Germ-cell neoplasia in situ (GCNIS) and calcifications in the left testicle, and a seminoma, 0.3 cm in greatest dimension with GCNIS and calcifications in the right testicle. The pathologic staging was pT2pNX for the left testicle and pT1pNX for the right testicle. Computed tomography (CT) revealed two mildly enlarged left sided para-aortic retroperitoneal lymph nodes. Radical pelvic lymph node dissection was performed. The pathology report showed four para-aortic lymph nodes positive for metastatic carcinoma. Tumor was positive for CD30 in the embryonal component, positive for Glypican-3 in the yolk sac tumor component, and seminoma was positive for PLAP. The final staging was IIB for the left testicle and IA for the right testicle. He underwent 4 cycles of Etoposide and Cisplatin chemotherapy (EP). He is in complete remission after 10 months of his diagnosis. Results (if a Case Study enter NA) NA. Conclusion The SBTGCTs with discordant subtypes represent a rare entity with no standard therapy. Our patient was treated with 4 cycles of chemotherapy and achieved complete remission.

Heat stress is a principal factor limiting production of animal protein in subtropical and tropical regions, and its impact is expected to increase dramatically. Development of effective strategies to improve the ability to cope with heat stress is imperative to enhance productivity of the livestock industry and secure global food supplies. However, selection focused on production and ignoring adaptability results in beef animals with greater metabolic heat production and increased sensitivity to heat stress. The goal of this research is to describe novel traits which can be used to characterize genetic pathways for thermotolerance which are independent or positively associated with production performance. Variance components, heritabilities, additive genetic correlations, and phenotypic correlations were estimated for skin histology characteristics, hair characteristics, body temperature under high temperature-humidity index (THI) conditions, and ultrasound carcass traits on 330 heifers from the University of Florida multibreed herd. A high heritability of 0.69 was estimated for the sweat gland area. The heritability for body temperature under high THI conditions was estimated to be 0.13 which is similar the heritability estimated reported for rectal temperature in a Brahman x Angus crossbred population (0.19; Riley et al., 2012) and dairy cattle (0.17; Dikmen at al., 2012). Sweat gland area had a negative genetic correlation with sweat gland depth (-0.49), short and long hair length (-0.45 and -0.28, respectively), and body temperature under high THI conditions (-0.65). These negative correlations suggest a similarity in the genetic control underlying these traits which would allow for selection of animals with large sweat glands, short hair (both topcoat and under coat), and able to maintain a lower body temperature under high THI conditions. More importantly, although weak, the genetic correlations between sweat gland area and the two production traits (backfat and intramuscular fat) were favorable (0.22 and 0.20, respectively).

This study investigated the relationship between thermotolerance and residual feed intake (RFI) in Bos-indicus influenced replacement beef heifers. Multiple individual vaginal temperatures (VT) collected during the summer in Florida were used to select the most (n = 14; thermotolerant) and least (n = 13; non-thermotolerant) heat tolerant heifers to undergo a feed efficiency test in the fall. The maximum initial VT difference between groups was of 0.19 and 1.2 ± 0.065 °C (P < 0.01) for thermotolerant and non-thermotolerant heifers, respectively. Heifers (398 ± 11.3 kg; approximately 720 d of age) were randomly allocated to four concrete-floored pens equipped with two GrowSafe feed bunks each and received a common ad libitum total mixed ration (16.9% crude protein and 52% total digestible nutrients) for 56 d (14 d adaptation and 42 d evaluation period). Body weight (BW) was collected on d -1, 0, 14, 28, 41, and 42, while VT was recorded (10 min intervals for 4 consecutive d) from d 29 to 32, using temperature probes placed intravaginally with a hormone-free controlled internal drug release device. Final BW, average daily gain (ADG), dry matter intake (DMI), DMI as a percentage of BW, RFI, and VT were analyzed as a completely randomized design. Final BW, ADG, DMI, and VT collected during the feeding period were not affected by thermotolerance phenotype (P ≥ 0.42); however, heifers previously classified as thermotolerant had decreased RFI (P = 0.01; -1.32 vs. 1.27 ± 3.31 kg, respectively) and DMI as a percentage of BW (P = 0.01) when compared with non-thermotolerant heifers. In conclusion, Bos-indicus influenced replacement beef heifers previously classified as thermotolerant based on multiple vaginal temperature measurements collected throughout the summer had decreased residual feed intake when measured in the fall, indicating the potential of more heat tolerant heifers to be more feed efficient.

Summary Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding UK National Institute for Health Research Health Technology Assessment Programme.

Interventional radiology has made significant progress to the care of severe acute pancreatitis complications with the introduction of percutaneous procedures. More recently, radiologic intervention has become the gold standard in treating a rare condition like pancreatic pseudoaneurysms. We report the case of an 40 years old male, heavy drinker and smoker, at the second episode of acute pancreatitis that developed an pseudoaneurysm cured through angiographic embolotherapy.

Anaerobic digestion of organic matter with high moisture content has proven to be a suitable method for disposal of wet organic residuals with several advantages compared to other treatment technologies. This paper aimed at evaluating the theoretical and experimental biomethane potential of food processing residuals that are responsible for negative environmental impact, with exemplification for the potato processing waste. The biomethane potential is a useful parameter to assess the economic efficiency of anaerobic digestion processes as it can considerably influence the efficiency and the economic feasibility of the energy recovery technologies. Both experimental and theoretical biomethane potentials of potato waste in mesophilic anaerobic digestion as well as biodegradability of the substrate were estimated. Moreover, effects of microalgal extract addition on the digestion of potato waste were examined in an attempt to stimulate the anaerobic digestion. Cone model and a modified Gompertz model were used to predict the dynamics of biomethane production.

Summary Background The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. Methods In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of −20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than −20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. Findings Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13–CT-P13 group and 55 to the CT-P13–infliximab group) and 109 to initiate infliximab (54 to the infliximab–infliximab group and 55 to the infliximab–CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference −4·9% [95% CI −16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13–CT-P13 group, 34 [62%] in the CT-P13–infliximab group, 37 [69%] in the infliximab–infliximab group, and 40 [73%] in the infliximab–CT-P13 group). Interpretation This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. Funding Celltrion, Pfizer.

Introduction/Objective The brown recluse spider, Loxosceles reclusa, is commonly found in the southern and central United States and is known for its venomous bite. It has six eyes, uniformly colored abdomen and legs, is around 1 cm in length and prefers to live in warm, dark and dry places. Its bite in humans can cause skin necrosis as well as more severe manifestations including acute hemolytic anemia, disseminated intravascular coagulation (DIC), rhabdomyolysis and renal failure. Methods/Case Report We present a case report of a 27 year old male with no known past medical history who was referred from another medical center with a critical hemoglobin of 3.6 g/dl and acute hemolytic anemia that was not responsive to packed red blood cell transfusion and intravenous immunoglobulin treatment. He reported of having bitten by a brown recluse spider 8 days ago on the right scapular region. He started developing wound and pain in the area 2 days later when he was admitted to the hospital for a day and treated with antibiotics. His white blood cell count (WBC) at the time was mildly elevated with near normal hemoglobin and was incidentally found to have COVID 19 positivity. After being discharged, he developed fever with chills, dark urine, body ache, headache, nausea and vomiting. When presented to our hospital, laboratory review exhibited normocytic normochromic anemia with elevated bilirubin and decreased haptoglobin showing a hemolytic picture. The patient also displayed severe leukocytosis (WBC count: 53.50) with absolute neutrophilia, lymphocytosis, and monocytosis. Monocyte distribution width (MDW) was 30.02. These changes were attributed to be reactive to venom effect and sepsis. The patient showed significant improvement with plasmapheresis. Results (if a Case Study enter NA) NA. Conclusion The diagnosis of systemic loxoscelism is often difficult and delayed. Brown recluse spider bites may not always present with sharp stings to be noticed and reported by the patient. Presence of another infectious condition, like COVID 19 in this case, may divert the diagnosis. An elaborate patient history, physical examination for bite wound and patient education may help in identifying the cause early. Spider bites should be considered as a differential diagnosis in a patient with dermonecrosis and abrupt onset hemolysis or sepsis. Prompt treatment can prevent development of DIC, renal failure and life threatening conditions.

Thermal stress in subtropical regions is a major limiting factor in beef cattle productions with around $370 million being lost annually due to reduced performance. About 45% of beef cattle in the United States are in the southern and southeastern states where tropical and subtropical climates are most prevalent. Cattle utilize sweating to dispense most of their excess heat allowing them to return to their thermoneutral zone. The objective of this study was to conduct a genome-wide association study on sweat gland area in the Multi-breed Angus-Brahman herd of the University of Florida. Skin samples were collected along the shoulder from 337 cows of varying Brahman and Angus percentages. Cows were genotyped with the Bovine GGP F250k array. The biopsies were processed into histology slides and then ImageJ software was used to measure sweat gland area. A general linear model was used to test the significance of breed composition and age group on sweat gland area. Breed composition and age group had a significant effect on sweat gland area (P < 0.0001 and P < 0.0001, respectively), with sweat gland area increasing with Brahman percentage. Quality control was conducted using BLUPF90 software including a call rate of 0.90 and a minor allele frequency of 0.01 which left 125,035 SNPs available for the single-step genome wide association analysis. BLUPF90 software was used to fit a single locus mixed model to test the effect of each marker. There were a significant SNPs located in the MINDY1 and PRUNE1 gene, which are involved in cell proliferation and induction of cell motility. These results show that with selection on these SNPs, can improve the ability of cattle to adapt to thermal stress.

Beef is high in key nutrients; however, it is often perceived as unhealthy because of its high fat content, particularly its saturated fat. The fat content of beef is controlled by multiple genetic factors and impacts meat quality traits. The objectives of this study were to 1) characterize the natural variation in fatty acid (FA) composition of Bos taurus indicus influenced beef cattle, 2) estimate phenotypic and genetic correlations of FA composition with carcass and meat quality traits, 3) use genome-wide association (GWAS) to identify genes with the greatest effect on FA composition, and 4) use gene network analysis to identify genes with small effects on FA content. The following traits were recorded on 1,066 Brangus steer: carcass weight (kg; 373 ± 36.3); marbling (436 ± 84.2); quality grade; back fat (cm; 1.6 ± 0.6); ribeye area (cm2; 83.3 ± 9.5); yield grade (3.2 ± 0.9); Warner-Bratzler shear force (kg; 5.1 ± 1.0); and 27 FA [saturated (%; 47.6 ± 3.1), monounsaturated (%; 46.3 ± 3.5), and polyunsaturated (%; 6.1 ± 2.0)]. Carcass traits had weak beneficial correlations to FA composition suggesting the possibility to manage or select for beef with less saturated fat without negatively impacting meat quality. GWAS identified four QTL and gene network analysis identified 177 genes related to lipid storage, transportation, and modification.

Heat stress in cattle has recently received growing attention because of anticipated increases in environmental temperature by global warming. Heat stress limits the production efficiency of cattle, and it is one of the principal causes of economic loss for beef cattle producers in these environments. Thermotolerance can be defined as the ability to maintain optimal growth, feed intake, and reproduction under the presence of heat stress, and it varies among individual animals and breeds. The objectives of the analysis were to investigate the amount of variation on epidermis thickness, test the effect of breed composition and age group on skin histology traits and to conduct a genome-wide association study on skin properties of beef cattle, focusing on the epidermis thickness. Skin biopsy samples were collected from 318 heifers from a UF multibreed population (animals ranging from 100% Brahman to 100% Angus), genotyped with the Bovine GGP F250K chip. Quality control was conducted with BLUPF90 software, including a call rate of 0.90 and a MAF < 0.01. BLUPF90 software was used to fit a single locus mixed model to test the effect of each marker. Breed group and age group were included as fixed effects. There is a significant effect in breed group ((P < 0.0001) and in age group (P < 0.0001). This study shows there is a large amount of variation in epidermis thickness across and within breed groups. Significant SNPs for the thickness of the epidermis were found in the HBEGF gene, which is a protein coding involved in several processes, including epidermal growth factor receptor signaling pathway and there is a variation across breed Skin histology traits are fundamental for the ability to lose heat more efficiently and allow the maintenance of normal body temperatures under extreme conditions. This study could contribute toward improving cattle’s adaptation to thermal stress.

Angiogenesis is the process of developing new blood vessels from pre-existing ones. This review summarizes the main features of physiological and pathological angiogenesis and those of angiogenesis activation and inhibition. In healthy adults, angiogenesis is absent apart from its involvement in female reproductive functions and tissue regeneration. Angiogenesis is a complex process regulated by the action of specific activators and inhibitors. In certain diseases, modulating the angiogenic balance can be a therapeutic route, either by inhibiting angiogenesis (for example in the case of tumor angiogenesis), or by trying to activate the process of new blood vessels formation, which is the goal in case of cardiac or peripheral ischemia.

Funding Acknowledgements Type of funding sources: None. Background. Transcatheter aortic valve replacement (TAVR) prostheses have better hemodynamics compared to surgical prostheses, with lower incidence of prosthesis-patient mismatch (PPM). Nonetheless, this complication is neither rare nor benign in the expanding population of TAVR patients (pts). Data regarding the effect of TAVR PPM on cardiac function is scarce. Our aim was to determine the short-term impact of PPM on left atrium (LA) function in patients undergoing transfemoral TAVR. Methods. One hundred forty-three consecutive pts (76.3 ± 7.5 yrs, 74 men) considered to be at high risk for SAVR were enrolled and examined before and 30 days after TAVR. All pts underwent a comprehensive echocardiogram, including speckle tracking echocardiography (STE) for LA and left ventricular (LV) strain analysis. Longitudinal LA strain parameters were assessed from the apical 4-chamber view. Peak values of global longitudinal LA strain (LAε) and LA systolic strain rate (SSr, reservoir function) and early diastolic strain rate (ESr, conduit function) were measured in all. Contractile LA function (late diastolic strain rate, ASr) was assessed in patients in sinus rhythm (106 pts). Results. Fifty-five pts (38%) had PPM (defined as an indexed effective orifice area, EOA ≤0.85 cm2/m2). Most of these pts (71%) had moderate PPM (indexed EOA between 0.65 and 0.85 cm2/m2). No significant differences in age (76.4 ± 8.1 vs 76.3 ± 7.2 yrs, p = 0.9), gender (p = 0.2), body surface area (p = 0.8), body mass index (p = 0.2) and the presence of cardiovascular risk factors (p > 0.2 for all) were observed between pts with and without PPM. The severity of post-TAVR aortic regurgitation was mild in 92 pts (64%) and moderate in 12 pts (8%) without any significant difference between pts with and without PPM. The post-TAVR prevalence of ³moderate mitral regurgitation was not different between the two groups (p = 0.40). After TAVR, there were no significant differences in terms of indexed LV mass, volumes, ejection fraction (p > 0.5 for all). LV global longitudinal strain was also similar between groups (-13.7 ± 4.3 vs -14 ± 3.6%, p = 0.7). Although LA volumes were similar between patients with and without PPM (47.8 ± 12.4 vs 49.3 ± 20.3 ml/m2, p = 0.6), in the mismatch-group we found a significantly reduced systolic global LA strain (12.7 ± 6.2 vs 15.9 ± 7.9%, p = 0.009) and impaired LA contractile function (ASr: -1.0 ± 0.4 vs -1.2 ± 0.5, p = 0.03). Parameters of LV diastolic function were also worse in the mismatch-group, with an E/e’sep ratio of 22 ± 10 vs 17 ± 7, p = 0.01. Conclusions. In our study group TAVR was associated with an incidence of PPM of 38%. The short-term follow-up of these patients revealed a significantly impaired LA function and increased LV filling pressure in patients with PPM compared to those without PPM. To our knowledge, this is the first report about the effect of PPM on the LA global and contractile function.

Bos taurus indicus cattle have superior ability for regulation of body temperature during heat stress due to a number of physiological and cellular level adaptive traits. The objectives of this study were to quantify the change in body temperature in heifers with various proportions of Brahman genes per unit increase in heat stress as measured by THI and to assess the impact of skin properties on the phenotypic plasticity. A total of 299 two-year old heifers from six breed groups ranging from 100% Angus to 100% Brahman were evaluated under hot and humid conditions during 2017 and 2018 summer days. The plasticity in body temperature of breed groups in response to environmental challenges was estimated using a random regression mixed model. Six mm skin biopsies were collected from the right side of sixth thoracic bone of each heifer. Cross-sections of biopsy samples with a thickness of 7 µm were stained with Hematoxilin–Eosin technique. The number and area of sweat and sebaceous glands and the thickness of dermis and epidermis were determined using the ImageJ program. The 100% Brahman group had the lowest intercept and slope (38.66 and 0.18) representing the body temperature under the low THI conditions and the increase in body temperature for 2 units of THI, respectively. Except for the 100% Angus group, which had a slightly higher intercept (38.68), all other breed groups had lower intercepts. Body temperature in the 100% Angus heifers increases by 0.42 for every 2 units of THI. There was a significant linear effect of Brahman percentage on the sweat gland size, with the 100% Brahman having the largest sweat gland size (203.57µm2) and purebred Angus the smallest (94.31µm2). Effective strategies will require the identification of the genes conferring the superior thermotolerance in Brahman cattle.

Expression QTL mapping provides information about genetic variant with modulatory effects on gene expression which are useful for understanding the genetic architecture of complex phenotypes. This mapping allows for uncovering of genomic regions associated with transcription regulation of genes which can be related to phenotypic variation when they colocalize with QTLs (cis and trans effects), providing a molecular basis for the phenotype-genotype association. The objectives of the present research were to perform eQTL mapping for meat quality traits in longissimus dorsi muscle and to uncover genes whose expression is influenced by local or distant genetic variation. A total of 120 steers from the University of Florida Beef Unit multibreed Angus-Brahman herd born between 2013 and 2014 were used in this study. The first three principal components from a principal component analysis for all meat quality phenotypes were used to construct a meat quality index. Eighty animals were selected based on extreme meat quality index for mRNA sequencing and 100 bp paired-end reads were mapped against to the Btau_4.6.1 reference genome. eQTL mapping was performed using 112,042 SNPs and 8,588 genes. A cis QTL was defined as an SNP located no more than 1 Mb upstream of the transcription start site or downstream of the transcription end site of an annotated gene. Polymorphisms associated with expression of at least 20 genes in the case of eQTL were considered hot spots. The harboring or adjacent gene was defined as master regulators. Multiple cis eQTLs and sQTLs effects were identified and genes such as LSM2, SOAT1, TTN and TEK are a few examples of potential expression and splicing regulatory genes. A total of 27 expression and 13 splicing master regulator genes were uncovered, mainly cytoskeletal or membrane-associated proteins, transcription factors and DNA methylases.

Plant biostimulants, an emerging class of agricultural inputs, are complex products. The reproducibility of their specific action on plant metabolism and plant physiology, which lead to an enhanced nutrient use efficiency, stress tolerance and edible yield quality, is still a challenge. Development of quality insurance systems for plant biostimulants need complex investigation based on adapted analytical, physico-chemical and chemical methods. The objective of this work was to characterize commercial humate biostimulants through different analytical techniques (Fourier transform infrared spectroscopy - FTIR, thermogravimetric analysis- TGA) and to evaluate their textural and chemical (pH, C, N, humic acids, inorganic components) parameters. The first derivative curve from TG analysis showed decomposition of different compounds, classified according to the results obtained by FTIR. The humic substances determined by TGA method was comparable with the results obtained by gravimetric reference method. The inductively coupled plasma-optical emission spectrometry (ICP-OES) technique was applied to determine the inorganic elements either from the production process of humate or from raw materials, as well as for the control of humate in terms of requirements for safety and quality. Their complementary properties obtaining through different analytical techniques provide essential information on the chemical characteristics of the humate plant biostimulant formulations.

The hydroxyapatite (HA) nano and microparticles were synthesized by wet-chemical precipitation in order to use them as drug carriers for biomedical applications. Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FTIR) were performed to assess their size, external morphology and chemical composition. The properties of HA particles as drug carriers for antibiotics delivery were evaluated with doxycycline and chloramphenicol. The amount of drug loading and release was determined by UV-Visible spectrophotometry. The antibacterial properties of loaded HA particles were evaluated using gram-positive Bacillus subtilis bacteria and gram-negative Pseudomonas aeruginosa bacteria. The synthesized particles of HA exhibit a high adsorption capacity (around 99%) and good controlled release properties for doxycycline. The adsorption of chloramphenicol on HA was extremely low (about 2%). According to the results, the compatibility between the drug and substrate is an important factor in the absorption process, and the hydroxyapatite is a very promising carrier for controlled release of antibiotics.

Bos taurus indicus cattle have the superior ability for the regulation of body temperature during heat stress due to a number of physiological and cellular level adaptive traits. The objectives of this study were to quantify the change in body temperature in heifers with various proportions of Brahman genes per unit increase in heat stress as measured by temperature–humidity index (THI) and to assess how different breed groups responded to varying intensity and duration of heat stress. A total of 299 two-yr-old heifers from six breed groups ranging from 100% Angus to 100% Brahman were evaluated under hot and humid conditions during 2017 and 2018 summer days. Two strategies were used to estimate the plasticity in body temperature of breed groups in response to environmental challenges: 1) a random regression mixed model was used to estimate reaction norm parameters for each breed group in response to a specified environmental heat stress and 2) a repeated measures mixed model was used to evaluate the response to different environmental heat loads. The reaction norm model estimated an intercept and slope measuring the change in body temperature per unit increase in THI environmental heat stress for different breed groups of animals and allowed the identification of genotypes which are robust, with low slope values indicative of animals that are able to maintain normal body temperature across a range of environments. The repeated measures mixed model showed that Brahman cattle have an advantage under moderate or high heat stress conditions but both Angus and Brahman breed groups are greatly affected when heat stress is severe. A critical factor appears to be the opportunity to cool down during the night hours more than the number of hours with extreme THI. With heat stress conditions predicted to intensify and expand into currently temperate zones, developing effective strategies to ensure sustainable beef production systems are imperative. Effective strategies will require the identification of the genes conferring the superior thermotolerance in Brahman cattle.

Background. Colonoscopy is a common performed procedure in Gastroenterology, and it’s widely used for diagnosis, treatment and surveillance of a wide range of conditions and symptoms. Properly performed, it’s generally safe, more accurate than a virtual colonoscopy and well-tolerated by patients. The completion of a colonoscopy is defined by cecal intubation with the visualization of colonic mucosa and distal terminal ileum when it’s possible. Patients and methods. We reviewed retrospectively all consecutive endoscopies database of the lower digestive tract, done over a period from 2014-2017 in our clinic. The recommended completion based on the latest guidelines ranges from 90-95% completion rate according to the indication. Results. 11214 consecutive colonoscopies were done. Overall cecal intubation was successful in 9456 procedures (87.3%). If we exclude the interventional procedures (414 procedures), where cecal intubation was not necessary, the main reasons of non-intubation were due to intolerance of the patients (388 patients), followed on the second place by patients with obstructive cancer (299 patients). The presence of diverticulosis, poor preparation for colonoscopy and post-surgical adhesions were significant findings in non-successful procedures. Conclusions. In normal daily practice, colonoscopy is completed in 88.01% of the procedures but we think that this result will stimulate the efforts to incorporate more quality measures and time in our endoscopy laboratory.

Water is an essential nutrient, but there are few recent studies that evaluate how much water individual beef cattle consume and how environmental factors affect an individual’s water intake (WI). Most studies have focused on WI of whole pens rather than WI of individual animals. Thus, the objective of this study was to evaluate the impact of environmental parameters on individual-animal WI across different seasons and develop prediction equations to estimate WI, including within different environments and management protocols. Individual daily feed intake and WI records were collected on 579 crossbred steers for a 70-d period following a 21-d acclimation period for feed and water bunk training. Steers were fed in 5 separate groups over a 3-yr period from May 2014 to March 2017. Individual weights were collected every 14 d and weather data were retrieved from the Oklahoma Mesonet’s Stillwater station. Differences in WI as a percent of body weight (WI%) were analyzed accounting for average temperature (TAVG), relative humidity (HAVG), solar radiation (SRAD), and wind speed (WSPD). Seasonal (summer vs. winter) and management differences (ad libitum vs. slick bunk) were examined. Regression analysis was utilized to generate 5 WI prediction equations (overall, summer, winter, slick, and ad libitum). There were significant (P < 0.05) differences in WI between all groups when no environmental parameters were included in the model. Although performance was more similar after accounting for all differences in weather variables, significant (P < 0.05) seasonal and feed management differences were still observed for WI%, but were less than 0.75% of steer body weight. The best linear predictors of daily WI (DWI) were dry mater intake (DMI), metabolic body weights (MWTS), TAVG, SRAD, HAVG, and WSPD. Slight differences in the coefficient of determinations for the various models were observed for the summer (0.34), winter (0.39), ad libitum (0.385), slick bunk (0.41), and overall models (0.40). Based on the moderate R2 values for the WI prediction equations, individual DWI can be predicted with reasonable accuracy based on the environmental conditions that are present, MWTS, and DMI consumed, but substantial variation exists in individual animal WI that is not accounted for by these models.

Consumers demand meat that is both healthy and palatable, 2 attributes of meat that are affected by lipid content. Many cattle in the southern United States are Bos indicus influenced, as this improves the ability to survive and thrive in these subtropical regions. However, these animals tend to have leaner carcasses and less marbled meat products. Thus, the objective of this study was to examine the effect of percent Brahman genetics on carcass characteristics, palatability, fatty acids profile, and minerals content in LM of steers from a multibreed population ranging from 100% Angus to 100% Brahman. Breed effect was significant for birth weight (P = 0.0003), weaning weight (P < 0.0001), HCW (P < 0.0001), dressing percentage (P = 0.0008), ribeye area (P = 0.002), quality grade (P < 0.0001), and marbling score (P < 0.0001), and all these traits except dressing percentage decreased as the percentage of Brahman increased. Among palatability traits, breed group had a significant effect only on tenderness (TEND) and connective tissue (CT) scores (P < 0.0001). Least squares means decreased from Angus (5.75 ± 0.13 TEND score and 6.29 ± 0.14 CT score, respectively) to Brahman (4.84 ± 0.10 TEND score and 5.49 ± 0.11 CT score, respectively) as indicated by a significant linear effect. Breed group significantly affected the percentage of several individual fatty acids, saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA), but not monounsaturated fatty acids (MUFA). The 100% Angus group had the highest percentage of SFA at 49.92%, which was significantly higher (P < 0.05) than the SFA percentage in the 50%, 75%, and 100% Brahman breed groups. Brangus animals also had an increased SFA percentage compared with the 100% Brahman animals (P < 0.05). No significant effect was identified for the concentration of PUFA across the 6 breed groups (P = 0.14). Least squares means decreased from 100% Angus to 100% Brahman for concentration of total fat, SFA, and MUFA (g/mg meat). The concentration of magnesium (P < 0.0001), phosphorus (P = 0.06), and potassium (P = 0.06) increased as the percentage of Brahman increased. Our study shows that breed has a significant effect on the fatty acid profile of beef. Cattle with high Brahman percentage, which are characterized by lower marbled meat, will present a more favorable healthfulness profile with reduced content of SFA and MUFA but the same content of PUFA as purebred Angus animals.

Heat stress is a cause of major economic losses to cattle producers, especially in tropical and subtropical environments. The objectives of this study were to assess the phenotypic variability in core body temperature and sweating rate and to evaluate the effect of coat type, temperament, and BW on core body temperature and sweating rate in Brangus heifers. During August and September of 2016, 725 Brangus heifers were evaluated on pasture in four separate groups (n = 200, 189, 197, and 139). Environmental measurements of dry bulb temperature (T(db)) and relative humidity (RH) were measured every 15 min during the entire time of data collection and the temperature–humidity index (THI) was used to quantify heat-stress potential. Coat score, sweating rate, chute score, exit score, and live weight were recorded as the animals passed through the chute. Vaginal temperature was recorded every 5 min for five consecutive days. There was significant variation in vaginal temperature between heifers in the same environmental conditions (σ(2)(u) = 0.049), suggesting opportunities for selective improvements. A repeatability of 0.47 and 0.44 was estimated for sweating rate and vaginal temperature, respectively, suggesting that one measurement would be able to adequately describe the sweating capacity or ability to control the body temperature of an individual. Vaginal temperature increased as THI increased, with approximately 1 h lag time in the animal’s response. Vaginal temperature (−0.047 °C, P = 0.015) and sweating rate were lower (−5.49 ± 2.12 g/(m(2)·h), P < 0.01) for heifers that demonstrated a calmer behavior in the chute. Animals with shorter, smoother hair coats had significantly lower vaginal temperatures when compared to animals with longer hair coats (P < 0.01). Also, heavier heifers in this study maintained lower (P < 0.0001) vaginal temperature than the lighter heifers. Our results showed that hair coat, temperament, and weight influenced vaginal temperature regulation.

Background Accurate assessment of disease activity in inflammatory bowel disease (IBD) is of paramount importance in decisions regarding treatment strategies. To apply a treat-to-target strategy, a tight assessment of activity is mandatory. MicroRNAs (miRNAs) are small, non-coding short (ribonucleic acid) RNAs that have a role in the regulation of genes and protein expression. MiRNAs have altered expression in multiple autoimmune disorders including IBD. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn’s disease (CD). Methods The study included 45 patients with histopathologically confirmed CD and active disease (defined as fecal calprotectin (fCal) > 50 ug/g and Short Endoscopic Score of Crohn’s Disease (SES-CD) > 3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fCal), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic (ROC) analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. Results Mean fCal was 1540 +/- 890 ug/g. Mean SES-CD was 8.9 +/- 4.2. Tissue and circulating miR-31 was significantly correlated with fCal (r = 0.81, r = 0.83, p < 0.01) and with SES-CD (r = 0.82, r = 0.79, p < 0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24 ± 1.57 vs. 3.70 ± 1.44; p < 0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated than in control serum samples (-2.07 ± 1.00 vs. 0.78 ± 0.42; p < 0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25 ± 0.93 vs. -4.69 ± 0.80, p = 0.03 for miR-200b, and -0.86 ± 0.96 vs. 0.39 ± 0.66, p < 0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated than in the control serum samples (p < 0.05). ROC analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. Conclusion Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active CD. Furthermore, circulating miR-31, miR-200b, and miR-200c may be used as non-invasive biomarkers for active CD patients.

Background MicroRNAs (miRNAs) are small, non-coding short (ribonucleic acid) RNAs that have a role in the regulation of genes and protein expression. MiRNAs have altered expression in multiple autoimmune disorders including inflammatory bowel diseases (IBD). This emerging role has led to investigations into miRNA expression profiles in IBD to understand the pathogenesis of these diseases and lead to clinical advances in this area. Due to shared pathways in fibrosis, miRNAs that have a potential role in intestinal fibrosis are worthy of investigation, and miR-192 seems to be associated with fibrosis and strictures in Crohn’s disease (CD). The study aimed to assess the expression levels of tissue and circulating miR-192 in patients with CD. Methods The study included 58 patients with CD and 31 subjects as controls for the validation cohort. Demographic and clinical data (including phenotype of the disease), biomarkers: fecal calprotectin (fCal), endoscopy data: Short Endoscopic Score of Crohn’s disease (SES-CD), the expression levels of miR-192 in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic (ROC) analysis was performed to assess the miR-192 expression level as a potential biomarker for stricturing phenotype of CD. Results The mean fCal was 345+/- 112 μg/g. The mean SES-CD was 3.4 +/- 1.1. Regarding disease phenotype, 26 (44.8%) had inflammatory phenotype, 32 (55.2%) had stricturing phenotype, and no patient had penetrant phenotype. Regarding location, 20 (34.5%) were ileal, 5 (8.7%) were colonic, and 33 (56.8%) were ileocolic. Strictures were all located in the terminal ileum. The expression level of miR-192 was significantly upregulated in CD tissue samples compared to the control tissue samples only in the patients with stricturing phenotype (8.27 ± 2.87 vs. 4.20 ± 1.94; p < 0.01), whereas in inflammatory phenotype miR-192 was downregulated (-3.47 ± 1.02 vs. - 4.30 ± 0.84; p < 0.01). Similarly, serum miR-31 expression level in CD patients was significantly upregulated than in control serum samples only in the patients with stricturing phenotype (4.07 ± 1.00 vs. 1.55 ± 0.91; p < 0.01), whereas in inflammatory phenotype miR-192 was downregulated (- 0.25 ± 0.79 vs. 0.76 ± 0.83; p < 0.01). There was a strong correlation between tissue and circulating miR-192 with stricturing phenotype (r = 0.89, r = 0.85, p < 0.05). ROC analysis revealed that the expression level of miR-192 could help to discriminate stricturing CD patients from other phenotypes with very good specificity and sensitivity. Conclusion MiR-192 is associated with stricturing phenotype in CD and could be a biomarker of intestinal fibrosis. Furthermore, circulating miR-192 could be a non-invasive biomarker of intestinal fibrosis.

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to ≥60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], ≥1.3; P≥0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P = 0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P = 0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3%vs. 0.1%, P = 0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P≥0.001). CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARETIMI 58 ClinicalTrials.gov number, NCT01730534

Anal canal duplication (ACD) is a very rare condition, diagnosed and treated mostly in childhood. Less than 90 cases have been reported in the literature so far. We are presenting a case of a young woman who underwent surgical excision of the duplication when she was 27 years old. The patient was unaware of her condition and was referred from a gynaecological office to the surgical department with a history of perianal discomfort and mucus discharge. Local examination showed an external orifice posterior to the anal opening, on the median line, which had the macroscopic appearance of a secondary anal orifice. The opening was about 0.5 cm in diameter. Exploration of the tract revealed a length of about 4 cm. MRI described the aforementioned tract, parallel to the anal canal, with no other anomalies mentioned. Under spinal anesthesia, with the patient in jackknife position, the accessory anal canal was surgically excised. The pathology report showed the presence of smooth muscle fibers and typical anal glands in the specimen. After a five-year follow-up, the patient showed no recurrence or any other related local symptoms. Absence of perianal abscess from the patient history, along with the macroscopic aspect of the opening similar to a secondary anal orifice on the midline, should raise the suspicion of ACD. Due to the lack of bothersome symptomatology, the patient did not seek any special investigations for her condition until she was in her late twenties. ACD is a very rare condition in adults that might pass unnoticed, but a midline opening posterior to the anus should always raise the suspicion of a secondary anal canal. Surgery is the only cure for this condition with good results after a proper pre-operative workout to reveal others simultaneous malformations.

The success of endovascular repair of abdominal aortic aneurysms remains limited due to the development of endoleaks. Sac embolization has been proposed to manage endoleaks, but current embolizing materials are associated with frequent recurrence. An injectable agent that combines vascular occlusion and sclerosing properties has demonstrated promise for the treatment of endoleaks. Moreover, the inhibition of aneurysmal wall degradation via matrix metalloproteinases (MMPs) may further prevent aneurysm progression. Thus, an embolization agent that promotes occlusion, MMP inhibition and endothelial ablation was hypothesized to provide a multi-faceted approach for endoleak treatment. In this study, an injectable, occlusive chitosan (CH) hydrogel containing doxycycline (DOX)—a sclerosant and MMP inhibitor—was developed. Several CH-DOX hydrogel formulations were characterized for their mechanical and sclerosing properties, injectability, DOX release rate, and MMP inhibition. An optimized formulation was assessed for its short-term ability to occlude blood vessels in vivo . All formulations were injectable and gelled rapidly at body temperature. Only hydrogels prepared with 0.075 M sodium bicarbonate and 0.08 M phosphate buffer as the gelling agent presented sufficient mechanical properties to immediately impede physiological flow. DOX release from this gel was in a two-stage pattern: a burst release followed by a slow continuous release. Released DOX was bioactive and able to inhibit MMP-2 activity in human glioblastoma cells. Preliminary in vivo testing in pig renal arteries showed immediate and delayed embolization success of 96% and 86%, respectively. Altogether, CH-DOX hydrogels appear to be promising new multifunctional embolic agents for the treatment of endoleaks. Statement of Significance An injectable embolizing chitosan hydrogel releasing doxycycline (DOX) was developed as the first multi-faceted approach for the occlusion of blood vessels. It combines occlusive properties with DOX sclerosing and MMP inhibition properties, respectively known to prevent recanalization process and to counteract the underlying pathophysiology of vessel wall degradation and aneurysm progression. After drug release, the biocompatible scaffold can be invaded by cells and slowly degrade. Local DOX delivery requires lower drug amount and decreases risks of side effects compared to systemic administration. This new gel could be used for the prevention or treatment of endoleaks after endovascular aneurysm repair, but also for the embolization of other blood vessels such as venous or vascular malformations.

The aim of this work is the synthesis of calcium carbonate (CaCO3) nano and microparticles and their application as biomaterials (vehicles) for the sustained release of doxycycline. CaCO3 micro particles were synthesized by water-in oil (W/O) emulsion method using emulsion liquid membranes with bis (2-ethylhexyl) phosphate (D2EHPA) as carrier, Span 80 as surfactant, and toluene and kerosene as organic solvents. The aqueous phases contained 1 M CaCl2, and 1 M Na2CO3, respectively. The Dynamic Light Scattering (DLS) data showed CaCO3 particles with sizes ranging from around 100 nm to 3500 nm. The CaCO3 particles with the average diameters around 600 nm attained an adsorbtion of doxycycline of maximum 97.9%, and a slow and steady release with a cumulative value of approximative 50% after ten days.

The Insentec Roughage Intake Control (RIC) system has been validated for the collection of water intake; however, this system has not been validated for water restriction. The objective of this validation was to evaluate the agreement between direct observations and automated intakes collected by the RIC system under both ad libitum and restricted water conditions. A total of 239 crossbred steers were used in a 3-d validation trial, which assessed intake values generated by the RIC electronic intake monitoring system for both ad libitum water intake ( = 122; BASE) and restricted water intake ( = 117; RES). Direct human observations were collected on 4 Insentec water bins for three 24-h periods and three 12-h periods for BASE and RES, respectively. An intake event was noted by the observer when the electronic identification of the animal was read by the transponder and the gate lowered, and starting and ending bin weights were recorded for each intake event. Data from direct observations across each validation period were compared to automated observations generated from the RIC system. Missing beginning or ending weight values for visual observations occasionally occurred due to the observer being unable to capture the value before the monitor changed when bin activity was high. To estimate the impact of these missing values, analyses denoted as OBS were completed with the incomplete record coded as missing data. These analyses were contrasted with analyses where observations with a single missing beginning or end weight (but not both) were assumed to be identical to that which was recorded by the Insentec system (OBS). Difference in mean total intake across BASE steers was 0.60 ± 2.06 kg OBS (0.54 ± 1.99 kg OBS) greater for system observations than visual observations. The comparison of mean total intake across the 3 RES validation days was 0.53 ± 2.30 kg OBS (0.13 ± 1.83 kg OBS) greater for system observations than direct observations. Day was not a significant source of error in this study ( > 0.05). These results indicate that the system was capable of limiting water of individual animals with reasonable accuracy, although errors are slightly higher during water restriction than during ad libitum access. The Insentec system is a suitable resource for monitoring individual water intake of growing, group-housed steers under ad libitum and restricted water conditions.

Onchocerca lupi is a filarial nematode, which infects the scleral conjunctival tissue of dogs, wolves and cats. Whilst adult nematodes localize in the conjunctive tissue of sclera or in the retrobulbar, microfilariae are found in the skin, and they are rarely diagnosed in asymptomatic animals. Since the first report of human ocular infection 5 years ago, up to 10 zoonotic cases have been identified in patients worldwide. We report, for the first time in Romania, three cases of canine ocular onchocercosis in dogs. Fragments of the harvested worms were characterized morphologically and molecularly. This article expands knowledge on the distribution of this parasite in Eastern Europe and sounds an alarm bell for ophthalmologists about the possible occurrence of human cases of O. lupi infection.

Over the last few decades, copper‑containing amine oxidase (Cu‑AO) from vegetal sources, and belonging to the class of diamine oxidase, has been documented to exhibit beneficial effects in both in vivo and ex vivo animal models of inflammatory or allergic conditions, including asthma‑like reaction and myocardial or intestinal ischemia‑reperfusion injuries. The aim of the present study was to assess the potential of vegetal Cu‑AO as an anti‑inflammatory and an antiallergic agent and to clarify its antioxidant properties. In cell‑free systems, the reactive oxygen species and reactive nitrogen species scavenging properties of Cu‑AO that is purified from Lathyrus sativus were investigated. Its effect on the formyl‑methionyl‑leucyl‑phenylalanine peptide (fMLP)‑activated cellular functions of human neutrophils were subsequently analyzed. The obtained results demonstrated that Cu‑AO is not a scavenger of superoxide or nitric oxide, and does not decompose hydrogen peroxide. However, it inhibits the fMLP‑dependent superoxide generation, elastase release and cell migration, and interferes with the process of calcium flux, supporting the idea that plant Cu‑AO can interact with human neutrophils to modulate their inflammatory function. Therefore, the importance of these properties on the possible use of vegetal Cu‑AO to control inflammatory conditions, particularly intestinal inflammation, is discussed in the current study.

Background Anemia is common in patients (pts) with severe aortic stenosis (AS). Untreated anemia and severe AS are individually associated with the development of heart failure, however data regarding the potential detrimental effect of anemia on left ventricular (LV) function and prognosis in pts with severe AS are controversial. Aim To investigate the impact of anemia on clinical status, echocardiographic parameters and prognosis in pts with severe AS and preserved LV ejection fraction (LVEF). Methods Consecutive patients with severe AS (aortic valve area [AVA] index ≤ 0.6 cm2/m2) and preserved LVEF (>50%) referred to our echocardiography laboratory were prospectively screened. All patients underwent complete clinical examination and comprehensive echocardiography, including speckle tracking-derived measurements of LV and left atrial (LA) strain. Baseline clinical variables included NYHA class, cardiac risk factors, haemoglobin (Hb) level and glomerular filtration rates (GFR, by MDRD formula). The definition of anemia was based on gender-specific cut-off values, as recommended by the WHO (Hb Results The study population included 264 patients (pts) (66 ± 11 yrs, 147 men). Anemia was present in 64 pts (24%). Aortic valve replacement (AVR) was performed in 151 pts. Dividing the study population into 2 groups, according to the presence/absence of anemia, no significant differences were found between groups regarding: age (p = 0.09), body surface area (p = 0.6), LVEF (62 ± 7 vs 63 ± 6%, p = 0.2), LV Global Longitudinal Strain (-15.2 ± 4 vs -14.7 ± 3 %, p = 0.4), LV mass index (p = 0.9), mean aortic gradient (p = 0.2) and indexed AVA (0.40 ± 0.09 vs 0.39 ± 0.09 cm2/m2, p = 0.6), or presence of significant coronary artery disease (p = 0.9). Compared to pts with normal Hb level, in pts with anemia NYHA class (p = 0.03), brain natriuretic peptide values (p = 0.004), lateral E/e’(16.2 ± 6.9 vs 13.7 ± 6.3, p = 0.01) and average E/e" ratio (15.9 ± 5.9 vs 14.1 ± 5.3, p = 0.03), LA volume index (54.3 ± 16.9 vs 45.0 ± 12.1 ml/m2, p Conclusions In our study including pts with severe AS and preserved LVEF, patients with baseline anemia presented worse functional status and LV diastolic dysfunction and increased 3-year all-cause mortality compared to those with normal Hb levels. However, in pts who underwent surgical AVR, there was no impact of baseline anemia on 3-year survival.

Background Transcatheter aortic valve replacement (TAVR) reverses LV remodeling and improves overall cardiac function, but data regarding its effect on left atrial (LA) function is scarce. Our aim was to evaluate the short-term effect of TAVR on LA myocardial deformation parameters and the relationship between the improvement of LA function and baseline echocardiographic parameters. Methods Fourty-eight consecutive pts (75 ± 6 yrs, 28 men) considered to be at increased risk for surgical aortic valve replacement were enrolled and examined before and 30 days after TAVR. All pts underwent a comprehensive echocardiogram, including speckle tracking echocardiography (STE) for deformation analysis. Longitudinal LA strain parameters were assessed from the apical 4-chamber view. Peak values of global longitudinal LA strain (LAε) and LA systolic strain rate (SSr, reservoir function) and early diastolic strain rate (ESr, conduit function) were measured in all. Contractile LA function (late diastolic strain rate, ASr) was assessed in patients in sinus rhythm (39 pts). Results Compared with baseline, the mean indexed LV mass was significantly reduced after TAVR (141 ± 26 vs 160 ± 37 g/m2, p = 0.009) but the mean increase in LVEF was not statistically significant (51 ± 14% vs 47 ± 15%, p = 0.2). There was a significant reduction in systolic pulmonary pressure after TAVR (34 ± 12 vs 42 ± 13, p = 0.004). Although there was no significant decrease in indexed LA volume (51 ± 22 vs 56 ± 20 ml/m2, p = 0.3), the contractile LA function significantly improved 30-days after TAVR (mean ASr, -1.1 ± 0.5 vs -0.8 ± 0.4 %, p = 0.02). There was a tendency of improvement in global longitudinal LA strain (15 ± 7 vs 12 ± 6%, p = 0.06) and global longitudinal LV strain (-13 ± 4 vs -11 ± 5%, p = 0.06) as well. Parameters of LV diastolic function, including TDI derived e’ and E/e’ ratios were not significantly improved 30 days after TAVI. While LA volumes and function parameters were not significantly different between genders at baseline, the improvement of LA function was more frequently found in male pts (p = 0.05). There were no significant correlations between the improvement of LA function parameters and baseline echocardiographic parameters in our study group. The only predictor of LA booster function improvement was the baseline value of ASr (p = 0.01). Conclusions TAVR is associated with a significant recovery of LA function as assessed by STE, suggesting a reverse cavity remodeling. This was accompanied by a significant reduction in LV mass and systolic pulmonary pressure. Men seem to show a more significant improvement in LA contractile function, suggesting a gender-related LA response to chronic afterload reduction.

Thermoregulation is important for beef cattle but tends to be negatively correlated with production traits. The objective of this study was to determine the variation in core body temperature and to estimate genetic parameters of skin traits in Angus, Brahman, and different levels of crossbred heifers (n = 337) reared in hot and humid conditions. Core body temperature was recorded as vaginal temperature every 15 minutes for 5 consecutive days. Dry bulb temperature and relative humidity in the pasture were also measured every 15 min and used to calculate a temperature-humidity index (THI). Five mm skin biopsies were collected from the right side of sixth thoracic bone of each heifer. Cross-sections of biopsy samples with a thickness of 7 µm were stained with Hematoxilin–Eosin technique. The number and area of sweat and sebaceous glands, and the thickness of dermis and epidermis were determined using the ImageJ program. Data were analysed using PROC MIXED in SAS 9.4 with a model including the effect of breed, year, and their interaction. Genetic parameters were estimated using WOMBAT. Average core body temperature of Angus, 25%, 37.5%, 50%,75% and 100% Brahman were 39.50±0.05, 39.30±0.04, 39.15±0.05, 39.2±0.0, 39.03±0.05, 39.04±0.05, respectively. Brahman heifers had lower core body temperature compared to Angus heifers (P = 0.0006). Heifers with smaller and more numerous sweat glands had higher (P < 0.01) and more variable core body temperature (P < 0.0001). Heritability of core body temperature under high and low THI was 0.44±0.006 and 0.61±0.003, respectively. Dermis and epidermis thickness had the lowest heritability (0.231±0.002) and the highest heritability (0.75±0.007), respectively. Heritabilities for the number of sweat glands and total sweat gland area were 0.375±0.02 and 0.432±0.006, respectively. In conclusion, thermoregulation was highly correlated with breed composition, number of sweat glands and the average size of sweat glands.