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The ovarian response to a standard chronogest + eCG treatment with plasma levels of insulin, insulin-like growth factor-I (IGF-I), thyroids, non-esterified fatty acids (NEFA), OH-butyrate (BHB) and urea-N (PUN) was studied in lactating Awassi ewes (n = 105) during the late-summer - early autumn transition period. The ewes were inseminated with diluted fresh semen after gestagen removal, and mated thereafter; 26 of them conceived at the fixed-time AI (fix AI; conception rate is calculated from lambing dates). Ovarian function was monitored by milk progesterone (P4) profiles. Before synchronization, the ovary was still acyclic in 33 and already cyclic in 72 ewes. Twenty-nine and 43 of the cyclic animals were in the follicular and luteal phases, respectively. After gestagen removal almost all (n = 104) ewes ovulated, although at AI elevated P4 levels related to the presence of partially luteinized follicles, and short-lived CL-s were observed in 10 and five animals (none of them re-conceived at the fixed time AI). Cycling ewes showed higher insulin and IGF-I levels than the acyclic animals, and those who had not conceived had higher PUN than the pregnant ones. The other metabolic parameters did not differ. Neither conception rate, nor the ovarian response was influenced by the pre-treatment.

Hyperoestrogenism causing progressive alopecia in neutered ferrets may be induced by ovarian remnant syndrome (ORS) and nodular hyperplasia of the adrenocortex (hyperadrenocorticism, NHA). The objective of the study was to determine whether a slow-release implant of a gonadotropin releasing hormone (GnRH) analogue, deslorelin, has any value in therapy of hyperoestrogenism of adrenocortical origin (NHA). Three supposed cases of NHA with alopecia and other clinical signs of hyperoestrogenism (n = 2 spayed females in oestrous and n = 1 castrated male) were treated with a subcutaneous implant of 4.7 mg deslorelin acetate. Blood samples were collected, and plasma levels of estradiol (E2) were determined just before, and some weeks after treatment. For realistic monitoring, blood samples for E2 determination were also taken from intact, healthy (untreated control) females after the beginning of heat (n = 5), or 9-21 days after, with hCG induced ovulation (n = 6), or out of breeding season (n = 3). Before treatment, all three alopecic ferrets showed elevated E2 concentrations (99.45-139.9 pmol/l) similar to the untreated control females in oestrous (61.6-123.02 pmol/l) (P = 0.229). Some weeks after the deslorelin administration, the hair of these ferrets began to grow again and the elevated E2 concentrations significantly decreased compared to the pre-treatment values (P = 0.035). E2 concentrations reached the basal level (12.89-16.08 pmol/l) typical for that of the untreated control females in anoestrus or in luteal phase (12.0-30.58 pmol/l) (P = 0.137). All treated ferrets were examined again 19-21 months after implant insertion (the implant still being present) and all of them had normal hair and were clinically healthy. These observations prove that deslorelin can suppress the E2 production of NHA, and is therefore a useful tool in the therapy of hormonal alopecia neutered ferrets.

Metabolic and endocrine characteristics of pregnancy toxemia are well documented in small ruminants, but less known in other species. The objective of this study was to measure plasma levels of certain metabolites and metabolic hormones related to the energetic status in blood from sick and healthy, non-pregnant (control) ferrets. Blood was collected from moribund, hypothermic, late pregnant females suffering from pregnancy toxemia (n = 4) and from healthy female ferrets (n = 14) to measure glucose, ketone (βOH-butyrate, BHB), insulin, thyroxine (T4) and 3,3',5-triiodothyronine (T3) concentrations. In contrast to healthy animals, hypoglycemia, hyperketonemia, hypoinsulinemia and decreased T4 and T3 levels were detected in females with pregnancy toxemia and necropsy showed excessive hepatic lipidosis. In summary, it can be concluded that pregnancy toxemia caused by a negative energy balance in ferrets resembles the late-gestational hyperketonemia of twin-pregnant ewes, and moreover that similar endocrine changes may occur.

Healthy multiparous Holstein-Friesian cows (n = 22, parity: 2-4) from a large-scale dairy herd in Hungary were subjected to an intravenous glucose tolerance test 10-15 days after calving. AluI genotype of growth hormone, several plasma metabolites and metabolic hormones were determined, and current and previous lactation yields were recorded. We also used the Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) and its modified version (RQUICKIBHB) for the estimation of peripheral insulin sensitivity. The majority of cows (n = 18) was leucine homozygous (LL), four were heterozygous (LV) and there were no valine homozygous (VV) animals in the population. Current average milk production was not different between AluI genotypes, but LV cows tended to have higher 305-day previous lactation yields (P = 0.13). AluI polymorphism was not associated with any of the calculated glucose and leptin parameters of the intravenous glucose tolerance test (P > 0.58). Heterozygous cows were prone to higher basal insulin levels (P = 0.064), longer time to reach half of the maximal and basal insulin concentrations (P = 0.035 and P = 0.054, respectively) and larger insulin area under the curve (P = 0.032). Both RQUICKI and RQUICKIBHB estimated decreased insulin sensitivity in LV compared to LL cows (P = 0.055 and P = 0.044, respectively). Higher plasma NEFA and BHB levels accounted for slower glucose disappearance and lower insulin release and insulin clearance rate (P < 0.05). Average yield was inversely related to glucose area under the curve (P = 0.040) and time to reach baseline concentration (P = 0.005). Plasma cortisol lowered glucose clearance rate (P = 0.040) and prolonged time to reach basal levels (P = 0.006). More weight loss was associated with higher glucose peak and prolonged glucose disappearance time (P = 0.055 and P = 0.024, respectively). All cows became cyclic and showed signs of estrus during the study period. There were no differences between leucine homozygous and heterozygous animals in the onset of ovarian activity and in the time of first observed estrus (P > 0.540). We conclude that Holstein-Friesian cows heterozygous for AluI polymorphism of the growth hormone gene may be more likely to develop insulin resistance during early lactation than leucine homozygous cows. Decreased insulin sensitivity could be part of a homeorhetic adaptation process that supports nutrient partioning for the use of the mammary gland and may allow LV cows to reach higher yields throughout lactation.

Pannon White (n = 12) male rabbits (weight: 4050 to 4500 g, age: 9 months) received 2 ml of a suspension containing purified T-2 toxin by gavage for 3 days. The daily toxin intake was 4 mg/animal (0.78 to 0.99 mg/kg body weight (BW)). Control animals (n = 12) received toxin-free suspension for 3 days. Since a feed-refusal effect was observed on the second day after T-2 administration, a group of bucks (n = 10) were kept as controls (no toxin treatment) but on a restricted feeding schedule, that is, the same amount of feed was provided to them as was consumed by the exposed animals. On day 51 of the experiment (i.e. 48 days after the 3-day toxin treatment), semen was collected, and pH, concentration, motility and morphology of the spermatozoa, as well as concentration of citric acid, zinc and fructose in the seminal plasma, were measured. After gonadotropin-releasing hormone (GnRH) analogue treatment, the testosterone level was examined. One day of T-2 toxin treatment dramatically decreased voluntary feed intake (by 27% compared to control, P < 0.05) and remained lower (P < 0.05) during the first 2 weeks after the withdrawal of the toxin. BW of the contaminated rabbits decreased by 88% on days 17 and 29 compared to controls (P < 0.05). No effect of toxin treatment was detected on pH and quantity of the semen or concentration of spermatozoa. The ratio of spermatozoa showing progressive forward motility decreased from 65% to 53% in the semen samples of toxin-treated animals compared to controls (P > 0.05). The ratio of spermatozoa with abnormal morphology increased (P < 0.05) in the ejaculates collected from the toxin-treated animals. T-2 toxin applied in high doses decreased the concentration of citric acid in seminal plasma (P < 0.05). No effect of T-2 toxin on the concentrations of the other seminal plasma parameters (fructose and zinc) was observed. T-2 toxin decreased the basic testosterone level by 45% compared to control (P < 0.01) and resulted in lower (P < 0.05) GnRH-induced testosterone concentration. Feed restriction, that is, less nutrient intake, resulted in more morphologically abnormal spermatozoa in the semen, but it did not cause significant loss in BW, motility of the spermatozoa, composition of the seminal plasma or testosterone concentration – its effect needs further examination.

Background: Sphingolipids are bioactive lipids that play a role in cancer development. However, the clinical role of sphingolipid (SPL)-related genes in oral cancer (OC) remains not fully understood., Objective: This study, aimed to examine the mRNA expression of 14 sphingolipid-related genes in oral cancer patients and their implication with clinicopathological features and prognosis., Methods: qPCR analysis was performed in 50 OC tissues and their matched surgical margins. Next, Kaplan-Meier, Cox regression, and Receiver operating characteristics (ROC) analysis were applied to evaluate the impact of sphingolipid-related genes expression on the prognosis of OC., Results: The genes SET, ACER3, SK1 and S1PR5 were predominantly up-regulated, while ABCG2, S1PR1, ABCB1 and SPNS2 were down-regulated in OC patients. Analyzing the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) data, which are predominantly composed of OC samples, these genes displayed a similar profile. In OC patients, high levels of SK1 were associated with lymph node metastasis, extracapsular invasion, desmoplasia, locoregional relapse, and disease status. Low levels of SPNS2 were associated with lymph node metastasis, perineural invasion, and disease status. Furthermore, OC and HNSC patients with higher SK1 expression demonstrated shorter disease-free survival (p= 0.0037; p= 0.0087), whereas those with lower SPNS2 expression exhibited shorter overall survival (p= 0.051; p= 0.0012). High levels of ACER3 and low levels of S1PR1 were associated with shorter disease-free and overall survival in HNSC patients., Conclusion: Several sphingolipid-related genes are deregulated in OC at the mRNA level and are associated with clinicopathological features and presented potencial for the prediction of poor prognosis in OC patients.

Background: The lymph node density (LND) is the number of positive metastatic lymph nodes divided by the total number of dissected lymph nodes. The purpose of this study was to evaluate LND as a prognostic factor in patients with laryngeal squamous cell carcinoma (SCC)., Methods: The study included 186 patients with laryngeal SCC submitted to laryngeal surgical treatment with neck dissection between January 2009 and December 2016. Clinical-pathological variables were assessed, as well as the cut-off point for LND., Results: LND value was calculated considering pN+ (LND = 0.060). The Kaplan-Meier curve (log-rank) related to cumulative survival demonstrated that patients with LND ≥ 0.060 had a higher mortality rate than those with LND < 0.060, presenting a more aggressive form of the disease, with earlier recurrence. However, only the LND ≥ 0.060 group had impact on both disease-free survival and overall survival., Conclusion: The LND proved to be an important index in the prognostic evaluation of larynx SCC patients having a direct relationship with disease recurrence. Patients with LND ≥ 0.060 should be considered for adjuvant therapy.

Introduction: Every year in the United States more than 600,000 ischemic stroke patients do not receive proven, effective stroke treatment or may not be medically eligible to receive the one medication endorsed by the U.S. Food and Drug Administration for acute ischemic stroke. The lack of treatment is due partly to shortages of neurological experts in rural and underserved areas. Telestroke programs can improve stroke care for stroke patients in rural and underserved settings by using interactive telecommunication technology that connects centrally located neurological experts to rural healthcare facilities. Many states have enacted policies and practices that facilitate telestroke access., Materials and Methods: We reviewed statutes and regulations in all 50 states that affect the adoption of telemedicine programs and describe examples of state-implemented programs in two states with policies that encourage telestroke use., Results and Discussion: This review presents evidence of the value and effectiveness of telestroke programs, as well as an explanation of common barriers and facilitators of telestroke, including licensing and credentialing rules, reimbursement issues, and liability concerns. Most states have adopted policies that affect the adoption of telestroke programs. Georgia and South Carolina are examples of states implementing stroke policies using a telestroke model to treat stroke patients in rural areas.

Reactions between methyldiphenylphosphane selenide, SePPh(2)Me, and different group 11 metal starting materials {CuCl, [CuNO(3)(PPh(3))(2)], AgOTf, [AgOTf(PPh(3))] (OTf = OSO(2)CF(3)), [AuCl(tht)], [Au(C(6)F(5))(tht)] and [Au(C(6)F(5))(3)(tht)] (tht = tetrahydrothiophene)} were performed in order to obtain several new species with metal-selenium bonds. The new complexes [CuCl(SePPh(2)Me)] (1), [AgOTf(SePPh(2)Me)] (2), [AuCl(SePPh(2)Me)] (5), [Au(C(6)F(5))(SePPh(2)Me)] (6) and [Au(C(6)F(5))(3)(SePPh(2)Me)] (7) were isolated and structurally characterized in solution by multinuclear NMR spectroscopy ((1)H, (31)P, (77)Se and (19)F where appropriate). Solid products were isolated also from the reactions between SePPh(2)Me and [CuNO(3)(PPh(3))(2)] or [AgOTf(PPh(3))], respectively. NMR experiments, including low temperature (1)H and (31)P NMR, revealed for them a dynamic behaviour in solution, involving the transfer of selenium from PPh(2)Me to PPh(3). In case of the isolated silver(i) containing solid an equilibrium between, respectively, monomeric [AgOTf(PPh(3))(SePPh(2)Me)] (3) and [AgOTf(PPh(2)Me)(SePPh(3))] (4), and dimeric [Ag(PPh(3))(μ-SePPh(2)Me)](2)(OTf)(2) (3a) and [Ag(PPh(2)Me)(μ-SePPh(3))](2)(OTf)(2) (4a) species was observed in solution. In case of the isolated copper(i) containing solid the NMR studies brought no clear evidence for a similar behaviour, but it can not be excluded in a first stage of the reaction. However the transfer of selenium between the two triorganophosphanes takes place also in this case, but the NMR spectra suggest that the final reaction mixture contains the free triorganophospane selenides SePPh(2)Me and SePPh(3) as well as the complex species [CuNO(3)(PPh(3))(2)], [CuNO(3)(PPh(2)Me)(2)] and [CuNO(3)(PPh(3))(PPh(2)Me)] in equilibrium. Single-crystal X-ray diffraction studies revealed monomeric structures for the gold(I) 6 and gold(III) 7 complexes. In case of compound 6 weak aurophilic gold(I)···gold(I) contacts were also observed in the crystal. DFT calculations were performed in order to understand the solution behaviour of the silver(I) and copper(I) species containing both P(III) and P(V) ligands, to verify the stability of possible dimeric species and to account for the aurophilic interactions found for 6. In addition, the nature of the electronic transitions involved in the absorption/emission processes observed for 6 and 7 in the solid state were also investigated by means of TD-DFT calculations.

In the title hydrated molecular salt, C(12)H(19)N(2)Se(+)·Br(-)·H(2)O, the two independent bromide anions lie on a twofold rotation axis. Strong intra-molecular N→Se inter-actions [2.185 (3) and 2.181 (3) Å] are established by both N atoms of the organic group in the cation, in trans positions to each other, with an N-Se-N angle of 161.6 (1)°, resulting in a T-shaped (C,N,N')Se core. In the crystal, dimeric associations are formed by Br⋯Se [3.662 (2) Å] and Br⋯H inter-actions [2.56 (6) and 2.63 (7) Å] involving two bromide anions, two cations and two water mol-ecules.

The reaction of [2-(Me(2)NCH(2))C(6)H(4)Se]M (M = Li, K) with the gold(phosphine) complexes [AuCl(PR(3))] gives the mononuclear gold-selenolate species [Au{SeC(6)H(4)(CH(2)NMe(2))-2}(PPh(3))] (1) or [Au{SeC(6)H(4)(CH(2)NMe(2))-2}(PPh(2)py)] (2), respectively. The treatment of the [2-(Me(2)NCH(2))C(6)H(4)Se]M with [Au(2)Cl(2)(mu-P-P)] [P-P = bis(diphenylphosphino)methane (dppm), bis(diphenylphosphino)ethane (dppe), 1,1'-bis(diphenylphosphino)ferrocene (dppf)] derivatives gives complexes with stoichiometry [Au(2){SeC(6)H(4)(CH(2)NMe(2))-2}(2)(mu-P-P)] [P-P = dppm (3), dppe (4), or dppf (5)]. These complexes exhibit a different structural framework, that is, 4 crystallizes as a chain polymer with intermolecular aurophilic bonding, while 5 shows an intramolecular Au(I)...Au(I) interaction. The gold(III) derivative Bu(4)N[Au(C(6)F(5))(3){SeC(6)H(4)(CH(2)NMe(2))-2}] (6) is obtained by reaction of [2-(Me(2)NCH(2))C(6)H(4)Se]K and Bu(4)N[AuBr(C(6)F(5))(3)], in a 1:1 molar ratio. These species exhibit luminescence which probably arises from a mixed (3)LMMCT and (3)MC excited state. The emission properties in these complexes seem to be useful for structural predictions and lead to the proposal of intermolecular aggregation in the solid state and frozen solution for complexes 1, 2, 3, whose crystal structures have not been elucidated.

In the title compound, C(24)H(20)P(2)S(5), the P atoms are arranged trans with respect to the S(3) group and the S=P-S-S systems have cisoid geometry, with an average S-P-S-S torsion angle of -56.7°. The dihedral angles between the two phenyl rings attached to the P atoms are 87.33 (12) and 75.67 (10)°. In the crystal structure, the mol-ecules are linked into chains running parallel to the a axis by weak inter-molecular C-H⋯S hydrogen bonds. Centrosymmetrically related chains are further connected by π-π stacking inter-actions, with a centroid-to-centroid distance of 3.795 (5) Å.

The title compound, C18H24N2Se3, consists of discrete molecules; owing to the presence of strong intramolecular N...Se interactions [N...Se = 2.671 (4) and 2.873 (4) A], the chalcogen Se atoms of the angular Se3 chain exhibit different coordination geometries, i.e. the terminal Se atoms are tricoordinated and exhibit a T-shaped environment of the CNSe2 core [N...Se-Se = 173.73 (9) and 172.29 (9) degrees], while the central Se atom is dicoordinated to the other two Se atoms, with an Se-Se-Se angle of 108.32 (2) degrees.

Cleavage of the Se-Se bond in [2-{O(CH(2)CH(2))(2)NCH(2)}C(6)H(4)](2)Se(2) (1) and [2-{MeN(CH(2)CH(2))(2)NCH(2)}C(6)H(4)](2)Se(2) (2) by treatment with SO(2)Cl(2), bromine or iodine (1 : 1 molar ratio) yielded [2-{O(CH(2)CH(2))(2)NCH(2)}C(6)H(4)]SeX [X = Cl (3), Br (4), I (5)] and [2-{MeN(CH(2)CH(2))(2)NCH(2)}C(6)H(4)]SeI (6). The compounds were characterized in solution by NMR spectroscopy (1H, 13C, 15N, 77Se, 2D experiments). The solid-state molecular structures of 1-3, 4.HBr, 5 and 6 were established by single crystal X-ray diffraction. In all cases T-shaped coordination geometries, i.e. (C,N)SeSe (1, 2), (C,N)SeX (3, 5, 6; X = halogen) or CSeBr(2) (4.HBr), were found. Supramolecular associations in crystals based on hydrogen contacts are discussed.

This study describes the effect of parity (multiparous versus primiparous) and body condition score (BCS) at calving (<3 or > or =3; scale 1-5) on variations of BCS, body weight (BW) and metabolic profiles in Holstein cows grazing on improved pastures. Forty-two cows were studied (21 multiparous and 21 primiparous) from 2 months before to 3 months after calving. BCS, BW and milk production were measured every 2 weeks. Blood samples were taken every 2 weeks to determine total protein, albumin, urea, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), cholesterol, aspartate aminotransferase (AST), calcium, phosphorus and magnesium. Primiparous cows had lower BCS during the early postpartum (PP) period and produced less milk than multiparous. In primiparous cows NEFA concentrations were higher during the early postpartum period; BHB levels were similar in both categories during this period. Primiparous cows showed a more unbalanced metabolic profile than multiparous cows, reflecting that they are recovering from the loss of BCS after calving with less success.

The effect of parity (multiparous vs primiparous) and body condition score (BCS; <3.0 or > or =3.0, lean vs fat) at parturition on metabolic and endocrine profiles from 1 month before to 2 months after parturition were studied in 42 Holstein cows grazing on improved pastures. BCS and milk production were determined every 2 weeks. Non-esterified fatty acids (NEFA), beta-hydroxy-butyrate (BHB), insulin, IGF-I, leptin, thyroxine (T4) and 3,3',5-tri-iodothyroinine (T3) were determined in plasma every 10 days. Progesterone was determined three times per week after parturition. Primiparous cows had a lower BCS during the early postpartum period and produced less milk than multiparous animals. Primiparous cows had higher NEFA concentrations and they presented more samples with BHB concentrations of >1 mmol/l than multiparous cows. Multiparous cows had higher T3, T4 and IGF-I concentrations, while fat cows had higher leptin and IGF-I concentrations. All hormone concentrations were diminished in the first week postpartum. Primiparous cows and fat cows presented a steeper decay of IGF-I and leptin around parturition than multiparous cows and lean cows. While thyroid hormones and IGF-I showed increasing concentrations from approximately day 30, leptin concentrations remained low until the end of the experimental period. The initiation of ovarian cyclicity was delayed in primiparous cows and especially in primiparous lean cows, consistent with longer intervals from parturition to first service and to conception. The endocrine signals most likely to inform the reproductive axis regarding a negative energy balance were IGF-I and leptin.

Six Finnish Ayrshire cows were challenged intramammarily with 1500 CFU of Escherichia coli (E. coli) into single udder quarters, and the challenge was repeated into contralateral quarters 3 weeks later. All cows received flunixine meglumine once, and 3 of them were also treated with enrofloxacin. At the 2nd challenge, treatments were changed vice versa. The development of mastitis was followed by monitoring of systemic and local clinical signs, and with serial milk and serum samples. Intramammary challenge with E. coli produced clinical mastitis in all cows, the severity of the disease varying greatly between the animals. No significant changes between the 2 treatment regimens or sequent challenges were found for any of the clinical parameters. The response of each cow followed the same pattern after both challenges; three of the cows became mildly and the other 3 either moderately or severely affected. Two severely affected cows had to be euthanized because of severe mastitis. Serum haptoglobin and amyloid-A concentrations peaked 2-3 days after bacterial challenge. Serum haptoglobin did not correlate with the severity of the disease. Serum amyloid-A rose gradually in the severely affected cows, and significant differences were found between severely versus moderately or mildly affected cows at day 4. Serum tumor necrosis factor alpha concentrations increased only in the severely affected cows. Serum cortisol response was prolonged in the severely diseased animals, and was significantly lower after the second challenge. Serum nitrite/nitrate concentration increased in the severely affected cows. This indicated excess nitric oxide production during acute E. coli mastitis. Strongly decreased milk production, and high bacterial growth in the infected quarters were best predictors for the outcome from acute E. coli mastitis.