Formation of (Aza)fulvenallene, Cyanocyclopentadiene, and (Aza)fluorenes in the Thermal Rearrangements of Indazoles, Azaindazoles, and Homoquinolinic Anhydride.

Flash vacuum pyrolysis (FVP) of pyrazoles and indazoles constitutes a valuable route to carbenes and nitrenes. In this study, we employed M062X and CCSD(T) calculations to provide a mechanistic rationale for the formation of fulvenallene and fluorenes from indazoles and the corresponding formation of azafulvenallene 15, cyanocyclopentadiene 19, and azafluorenes, e.g. 45, from azaindazoles, e.g. 12, and from homoquinolinic anhydride. The results reveal the importance of initial tautomerization in the pyrazole moiety of 7-azaindazole 12, which drives the mechanism toward 2-diazo-3-methylene-2,3-dihydropyridine 29 and hence 3-methylene-2,3-dihydropyridin-2-ylidene 26, followed by Wolff-type ring contraction to 1-azafulvenallene 15. This path has a calculated activation energy ∼10 kcal/mol lower than that for an alternate route involving ring opening to 3-diazomethylpyridine, dediazotization, and rearrangement of 3-pyridylcarbene to azacycloheptatetraene and phenylnitrene 24. FVP of 2,5-diphenyltetrazoles and phenyl(pyridyl)tetrazoles leads to nitrile imines, which cyclize to 3-phenylindazoles and -azaindazoles. Nitrogen elimination from these (aza) indazoles results in the formation of (aza) fluorenes, for which two alternate mechanisms are described: route A by rearrangement of (aza) indazoles to diazo(aza)cyclohexadienes and (aza)cyclohexadienylidenes and route B by rearrangement to diaryldiazomethanes and diarylcarbenes. Both paths are energetically feasible, but path A is preferred and corresponds to the azafluorenes obtained experimentally.

Thermal Rearrangement of Azulenes to Naphthalenes: A Deeper Insight into the Mechanisms.

The thermal rearrangement of azulene to naphthalene has been the subject of several experimental and computational studies. Here, we reexamine the proposed mechanisms at the DFT level. The use of different functionals showed that the HF-exchange contribution significantly affects reaction energies and barrier heights. Accordingly, all proposed pathways were investigated with the optimal method, M06-2X/6-311+G(d,p), which confirms the norcaradiene-vinylidene mechanism (A) as the dominant unimolecular route (Ea ≈ 76 kcal/mol) able to account for the major products of pyrolyses using 13C- or substituent-labeled azulenes. Moreover, a facile vinylidene-acetylene interconversion will scramble the terminal carbon atoms in the vinylidene. Several other potential intramolecular reaction mechanisms (B-E) are ruled out because of higher activation energies (>84 kcal/mol) and failure to reproduce the results obtained with substituted and 13C-labeled azulenes and benzazulenes. These experimental results also demonstrate that the proposed free radical or H atom-induced intermolecular methylene walk and spiran mechanisms cannot be major contributors, especially under flash vacuum pyrolysis conditions.

Azulene-Naphthalene, Naphthalene-Naphthalene, and Azulene-Azulene Rearrangements.

The mechanism(s) of thermal rearrangement of azulenes have been enigmatic for several decades. Herein, we have employed density functional theory (DFT) calculations at the M06-2X/6-311+G(d,p) level together with single-point calculations at the CCSD(T) level to assess possible mechanisms of the experimentally observed azulene and naphthalene automerizations. Of the two mechanisms proposed for naphthalene automerization, it is found that the benzofulvene (BF) route is favored over the naphthvalene mechanism by ∼6 kcal/mol and is energetically lower than the norcaradiene-vinylidene mechanism (NVM) for the azulene-naphthalene rearrangement (Ea ∼ 76.5 (74.6) kcal/mol). Moreover, contrary to older reports, we observe that a pathway involving indenylcarbene intermediates is a viable, alternate mechanism. Therefore, the naphthalene automerization is expected to take place during azulene pyrolysis, especially under conditions of low-pressure FVP, where it will be aided by chemical activation. Furthermore, thermal azulene-azulene isomerization is feasible through vinylidene-acetylene-vinylidene (VAV), dehydrotriquinacene (DTQ), and azulvalene (AV) pathways with activation energies lying below that required for the azulene-naphthalene conversion, i.e., the NVM. These results, together with the previously published NVM, provide reasonable explanations for most of the products of the thermal azulene-naphthalene rearrangement.

Mechanism-Based Inactivation of Cytochrome P450 Enzymes: Computational Insights.

Mechanism-based inactivation (MBI) refers to the metabolic bioactivation of a xenobiotic by cytochrome P450s to a highly reactive intermediate which subsequently binds to the enzyme and leads to the quasi-irreversible or irreversible inhibition. Xenobiotics, mainly drugs with specific functional units, are the major sources of MBI. Two possible consequences of MBI by medicinal compounds are drug-drug interaction and severe toxicity that are observed and highlighted by clinical experiments. Today almost all of these latent functional groups (e.g., thiophene, furan, alkylamines, etc.) are known, and their features and mechanisms of action, owing to the vast experimental and theoretical studies, are determined. In the past decade, molecular modeling techniques, mostly density functional theory, have revealed the most feasible mechanism that a drug undergoes by P450 enzymes to generate a highly reactive intermediate. In this review, we provide a comprehensive and detailed picture of computational advances toward the elucidation of the activation mechanisms of various known groups with MBI activity. To this aim, we briefly describe the computational concepts to carry out and analyze the mechanistic investigations, and then, we summarize the studies on compounds with known inhibition activity including thiophene, furan, alkylamines, terminal acetylene, etc. This study can be reference literature for both theoretical and experimental (bio)chemists in several different fields including rational drug design, the process of toxicity prevention, and the discovery of novel inhibitors and catalysts.

When a "Dimroth Rearrangement" Is Not a Dimroth Rearrangement.

In the Dimroth rearrangement of heterocycles, often pyrimidines, an exocyclic and a ring substituent are interchanged. However, the term Dimroth rearrangement is frequently used even when there is no knowledge of the reaction mechanism and alternatives are likely. Here, we have employed density functional theory (DFT) calculations at the M06-2X/6-311+G(d,p) level to determine the most plausible rearrangement pathways of 3-aminothiocarbonylquinazoline 5, tetrahydrofuranylpyrimidine 21, and 5-allyltriazocine 30. For the rearrangement of quinazoline 5 to 9, the [1,3]-sigmatropic shift of the thioamido group with an activation barrier of 26.7 kcal/mol is much preferred over the Dimroth rearrangement (∼46 kcal/mol). An even lower barrier of 21.6 kcal/mol applies to a stepwise [1,3]-shift. The migration of the tetrahydrofuranyl unit in pyrimidines like 21 → 23 can take place by means of a [1,3]-sigmatropic shift with a low barrier (≤17.5 kcal/mol) rather than a Dimroth rearrangement under acidic conditions and most likely also under neutral conditions (∼30 kcal/mol). In the rearrangement of 5-allyl-6-iminotriazocine 30 to 32, the [3,3]-sigmatropic shift (aza-Cope rearrangement) is preferred over the Dimroth mechanism under neutral conditions, but in the presence of acid, the azonia-Cope rearrangement of an allyl group and the true Dimroth rearrangement have comparable activation energies.

Effects of linseed oil and rumen undegradable protein:rumen degradable protein ratio on performance of Holstein dairy calves.

The present study evaluated the interaction effects of n-3 fatty acids (from linseed oil (LSO), 0 v. 2·5, % DM basis) with rumen undegradable:degradable protein (RUP:RDP) ratios (low ratio (LR) 27:73; high ratio (HR) 38:62 based on crude protein %) in dairy calves' starter diet. Forty-eight 3-d-old female Holstein dairy calves (41·5 kg of body weight (BW)) were allocated in a 2 × 2 factorial arrangements in the following treatments (n 12 calves/each): (1) no supplementation of LSO with LR (NLSO-LR); (2) no supplementation of LSO with HR (NLSO-HR); (3) supplementation of LSO with LR (LSO-LR) and (4) supplementation of LSO with HR (LSO-HR). The calves were weaned on day 53 of the experiment and remained in the study until day 73. Intake was not affected by LSO and RUP:RDP ratio. However, average daily gain (ADG) was improved with LSO supplementation. Feeding the HR diet increased ADG compared with the LR diet during the entire period. Final BW was greater in calves fed on the LSO than those fed the NLSO diet. Microbial protein production did not differ among treatments. Calves fed on LSO diets had greater feed efficiency than those which were not fed on LSO diets. The calves supplemented with LSO had greater wither and hip heights compared with the unsupplemented calves. The glucose, cholesterol, HDL and insulin concentrations increased in calves supplemented with LSO. In conclusion, the HR diet improved calves' performance post-weaning; however, LSO could enhance growth performance of dairy calves during the pre-weaning period.

Effects of physical forms of starter and milk allowance on growth performance, ruminal fermentation, and blood metabolites of Holstein dairy calves.

A 2 × 2 factorial study was conducted to evaluate the effects of milk allowance and physical forms of starter on growth performance, ruminal fermentation, and blood metabolites of Holstein dairy calves. A total of 48 calves [40.4 ± 1.55 kg of body weight (BW), n = 12 per treatment: 6 males and 6 females] were randomly assigned to 1 of the 4 treatments: (1) calves fed low milk allowance and finely ground (FG) starter feed [low-FG; 1.47 ± 2.12-mm geometric mean particle size (GMLP)], (2) calves fed low milk allowance and textured (TS) starter feed [low-TS, includes steam-flaked grains (corn and barley) with a pelleted supplement, GMLP 4.15 ± 1.77 mm], (3) calves fed high milk allowance and FG starter feed (high-FG); and (4) calves fed high milk allowance and TS starter feed (high-TS). The starter diets were blended with 7% of chopped alfalfa hay as a proportion of diet dry matter (DM). No milk refusal was observed in any treatments, and calves on both treatments were weaned from milk by wk 8 of the study using a gradual weaning procedure. We observed no interaction between milk allowance and physical forms of starter on feed intake, average daily gain, feed efficiency, BW, and structural growth. Calves fed high milk allowance had lower starter feed intake but greater feed efficiency and overall BW compared with those fed low allowance. Total DM intake and average daily gain were not different among treatments. Regardless of the physical form of starter feed, hip height, heart girth, the molar proportion of ruminal acetate, acetate to propionate ratio, plasma cholesterol, and high-density lipoprotein were greater, but ruminal total volatile fatty acids, the molar proportion of propionate, and plasma ß-hydroxybutyrate were lower in calves fed high milk allowance compared with those fed low allowance. Regardless of the milk allowance, calves fed the FG starter feeds had greater blood urea nitrogen concentrations compared with calves fed the TS starter diets. In conclusion, both forms of the starter feeds can be used when calves are fed high milk allowance with no negative effect on their performance.

Effects of step-down weaning implementation time on growth performance and blood metabolites of dairy calves.

The current study evaluated the effects of step-down weaning implementation time on starter feed intake, growth performance, blood metabolites, and ruminal pH in dairy calves. A total of 48 Holstein dairy calves (24 male and 24 female; 3 ± 1 d old; 41.2 ± 1.8 kg of body weight) were assigned (n = 12 per treatment; 6 male and 6 female) to 4 experimental treatments in a completely randomized block design. All calves were fed 6 L/d of milk from d 3 to 10 of age, and the treatments consisted of the following: calves were offered 8 L/d of milk from d 11 to 28 of age and then 4 L/d from d 29 to 63 (Step-28; total milk offered = 326 L); calves were offered 8 L/d of milk from d 11 to 42 of age and then 4 L/d from d 43 to 63 (Step-42; total milk offered = 382 L); calves were offered 8 L/d of milk from d 11 to 56 of age and 4 L/d from d 57 to 63 (Step-56; total milk intake = 438 L); and calves were fed 8 L/d of milk from d 11 to 63 of age and abruptly weaned (control; total milk offered = 466 L). All calves were housed individually in pens and had ad libitum access to water and solid feed throughout the experiment. All calves were completely milk weaned on d 64, and their performance was measured until d 80 of age. During the experiment, the starter intake (kg/d and % of body weight) was greater in calves in the Step-28 group compared with those in the other groups. However, the total metabolizable energy intake was greater in the Step-56 calves compared with the other calves. Overall, the average daily gain (ADG), feed efficiency (ADG/dry matter intake), and ADG/total metabolizable energy intake were similar across the treatments. Circulating glucose, ß-hydroxybutyrate, blood urea nitrogen, albumin, total protein, alanine aminotransferase, and aspartate aminotransferase, as well as ruminal pH, were not affected by the treatments. The implementation of step-down weaning in early life (4-6 wk of age) could stimulate solid feed intake compared with weaning at a later age with no negative effect on performance.

Poultry by-product meal as a replacement to xylose-treated soybean meal in diet of early- to mid-lactation Holstein cows.

The objectives were to compare the effectiveness of poultry by-product meal (PBM) with xylose-treated soybean meal (x-SBM) as a conventional protein source and rumen-undegraded protein (RUP):rumen-degraded protein (RDP) ratio on nutrient digestibility, nitrogen metabolism, and production of early- to mid-lactation Holsteins. Twelve multiparous cows averaging (mean ± SD) 50 ± 9 days in milk were randomly assigned to a replicated 4 × 4 Latin square design within a 2 × 2 factorial arrangement of treatments. Each period was 28 days in length. Treatments were RUP sources (PBM or x-SBM) with either a high or a low RUP:RDP ratio (high ratio = 40:60 or low ratio = 36:64; based on % of crude protein (CP)). Experimental diets were balanced to be similar in protein and energy contents (CP = 16.7% of DM; NEL = 1.67 Mcal/kg DM). Prior to diet formulation, an in situ pilot experiment was conducted to estimate the RUP fractions of x-SBM and PBM as 63.9% and 54.1% of CP, respectively. Treatments had no effect on ruminal pH and total volatile fatty acid (VFA) and molar percentage of individual VFAs. Treatments had no effect on total tract apparent digestibility of DM, OM, and neutral detergent fiber (NDF), with the exception of N that was greater in diets with a low RUP:RDP ratio (68.2 vs. 70.1% of DM). DM consumption was 0.70 kg/day higher when cows were fed PBM diet compared with x-SBM diet. No treatment effect was observed on milk yield and milk composition; however, milk protein yield and milk urea N were greater in cows fed PBM. Inclusion of PBM in the diet in substitution to x-SBM resulted in increased blood levels of urea N, cholesterol, and non-esterified fatty acid (NEFA). There was no interaction between the RUP source and the RUP:RDP ratio for urinary and fecal N excretion. Efficiency of N utilization expressed as milk N secretion as a proportion of N intake tended to be greater in cows fed PBM. Feeding diets with a low ratio of RUP:RDP increased efficiency of milk production expressed as milk yield as a proportion of total N excretion (fecal and urinary N). Feeding a diet with PBM supported milk production comparable with x-SBM and had positive effects on feed intake, milk protein yield, and milk N efficiency.

Evaluation of an education program based on the theory of planned behavior for salt intake in individuals at risk of hypertension.

This study was conducted to evaluate an education program based on the theory of planned behavior (TPB) for salt intake in individuals at risk of hypertension. This randomized controlled trial was conducted from February 2017 to December 2017 in Shahediyeh, Yazd Province, Iran. For this purpose, 140 people were selected and assigned to two groups of 70 each, namely, intervention and control. Data were gathered by a self-administered TPB based questionnaire, and also 24-h urinary sodium and potassium levels and systolic and diastolic blood pressure were measured. The intervention group received TPB based on a training package, while the control group received no intervention. Post-test was administered 2 months after completion of the intervention. Independent and paired t-tests, χ2 and analysis of covariance (ANCOVA) were used for data analysis. All mean scores on TPB constructs increased significantly except motivation to comply and power of control for intervention group. Average salt intake decreased in intervention group compared with the control group (-4.73 g/day �0.73 versus -0.24 g/day �0.94, P < 0.001), but systolic and diastolic blood pressure did not change significantly in intervention group compared with control group. TPB can be implemented along with other approaches in educational programs to reduce salt intake. Code: IRCT201701108803N3.

Effects of rumen-degradable protein:rumen-undegradable protein ratio and corn processing on production performance, nitrogen efficiency, and feeding behavior of Holstein dairy cows.

This study was conducted to investigate the effects of the ratio of rumen-degradable protein (RDP) to rumen-undegradable protein (RUP) and corn processing method on production performance, nitrogen (N) efficiency, and feeding behavior of high-producing Holstein dairy cows. Twelve multiparous Holstein cows (second parity; milk yield = 48 ± 3 kg/d) were assigned to a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Factor 1 was corn processing method [ground corn (GC) or steam flaked corn (SFC) with a flake density of about 390 g/L], and factor 2 was RDP:RUP ratio [low ratio (LR) = 60:40; high ratio (HR) = 65:35] based on crude protein (%). The crude protein concentrations were kept constant across the treatments (16.7% of DM). No significant interactions of main treatment effects occurred for lactation performance data. Cows fed 2 different RDP:RUP ratios exhibited similar dry matter intake (DMI), but those fed SFC showed decreased feed intake compared with those receiving GC (25.1 ± 0.48 vs. 26.2 ± 0.47 kg/d, respectively). Cows fed HR diets produced more milk than did those fed LR diets (44.4 ± 1.05 vs. 43.2 ± 1.05 kg/d, respectively). Milk fat content decreased but milk protein content increased in cows fed SFC compared with those fed GC. Feed efficiency (i.e., milk yield/DMI) was enhanced with increasing ratio of RDP:RUP (1.68 ± 0.04 vs. 1.74 ± 0.04 for LR and HR, respectively). Apparent N efficiency was higher in cows fed HR than in those fed LR (30.4 ± 0.61 vs. 29.2 ± 0.62, respectively). Compared with cows fed the GC-based diet, those receiving SFC exhibited lower values of N intake, N-NH3 concentration, and fecal N excretion. Cows receiving SFC-based diets spent more time ruminating (min/kg of DMI) than did those fed GC. Although these results showed no interaction effects of RDP:RUP ratio and corn processing method on performance, higher RDP:RUP ratios and ground corn can be effective feeding strategies for feed to lactating cows receiving high-concentrate diets.

Interaction between the physical forms of starter and forage source on growth performance and blood metabolites of Holstein dairy calves.

The objective of this study was to investigate the effects of the physical forms of starter and forage sources on feed intake, growth performance, rumen pH, and blood metabolites of dairy calves. Forty male Holstein calves (41.3 ± 3.5 kg of body weight) were used (n = 10 calves per treatment) in a 2 × 2 factorial arrangement of treatments with the factors being physical forms of starter (coarse mash and texturized) and forage source [alfalfa hay (AH) and wheat straw (WS)]. Individually housed calves were randomly assigned to 1 of the 4 dietary treatments, including (1) coarsely mashed (CM; coarse ground grains combined with a mash supplement) starter feed with AH (CM-AH), (2) coarsely mashed starter feed with WS (CM-WS), (3) texturized feed starter (TF; includes steam-flaked corn, steam-rolled barley combined with a pelleted supplement) with AH (TF-AH), and (4) TF with WS (TF-WS). Both starters had the same ingredients and nutrient compositions but differed in their physical forms. Calves were weaned on d 56 and remained in the study until d 70. All calves had free access to drinking water and the starter feeding at all times. No interaction was detected between the physical forms of starter feeds and forage source concerning starter intake, dry matter intake, metabolizable energy (ME) intake, average daily gain (ADG)/ME intake, ADG, and feed efficiency (FE). The preweaning and overall starter feed intake, dry matter intake, and ME intake were greater for calves fed TF starter diets than those fed CM starter diets. The ADG/ME intake was greater for calves fed TF starter diets than that fed CM starter. The FE was greater for calves fed TF starter diets compared with those fed CM starter during the preweaning, postweaning, and overall periods. The WS improved FE during the postweaning period compared with AH. The physical form of starter, forage source, and their interaction did not affect plasma glucose, triglycerides, and very low-density lipoprotein concentrations. Ruminal pH was greater for calves fed TF starter diets than those fed CM starter on d 30 of life. An interaction was observed between the physical forms of starter diets and forage source for ß-hydroxybutyrate on d 28. These results showed that when starter diets contained similar ingredients and nutrient contents, processing calf starters to reduce the number of fine particles can improve the growth performance in dairy calves. Furthermore, the provision of WS improved FE and ADG of calves during the postweaning period.

Performance, nutritional behavior, and metabolic responses of calves supplemented with forage depend on starch fermentability.

This study evaluated the interactive effects of forage provision on performance, nutritional behavior, apparent digestibility, rumen fermentation, and blood metabolites of dairy calves when corn grains with different fermentability were used. Sixty 3-d-old Holstein calves were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Dietary treatments were (1) steam-flaked (SF) corn without alfalfa hay (AH) supplementation (SF-NO), (2) SF corn with AH supplementation (SF-AH), (3) cracked (CR) corn without AH supplementation (CR-NO), and (4) CR corn with AH supplementation (CR-AH). All calves received the same amount of pasteurized whole milk and weaned on d 56 of the experiment; the study was terminated on d 70. Steam-flaked corn contained higher amounts of gelatinized starch in comparison with cracked corn (44.1 vs. 12.5% of total starch, respectively). Starter intake was not affected by corn processing methods or AH provision during the pre- or postweaning periods. However, we noted an interaction between corn processing methods and forage supplementation for starter intake during d 31 to 50 of the experiment, where calves fed on SF-AH starter had greater starter intake than those fed SF-NO starter, but the starter intake was not different between CR-NO and CR-AH fed calves. Furthermore, AH increased average daily gain (ADG) of calves fed an SF-based diet but not in calves fed a CR-based diet during the preweaning and overall periods. Interaction between forage provision and time was significant for ADG and feed efficiency, as calves supplemented with forage had higher ADG (0.982 vs. 0.592, respectively) and feed efficiency compared with forage unsupplemented calves at the weaning week. Forage supplementation resulted in more stable ruminal condition compared with nonforage-fed calves, as evidenced by higher ruminal pH (5.71 vs. 5.29, respectively) at postweaning and lower non-nutritive oral behavior around weaning time (55 vs. 70.5 min, respectively). The concentration of blood ß-hydroxybutyrate was also greater in calves supplemented with forage than in unsupplemented calves. Results of the present study indicated that performance response and skeletal growth were the same between 2 corn processing methods. Forage provision improved ADG of calves fed the SF-based diet, but not the CR-based diet throughout the study.

Effects of forage source and forage particle size as a free-choice provision on growth performance, rumen fermentation, and behavior of dairy calves fed texturized starters.

We investigated the interactive effects of forage source and forage particle size (PS) as a free-choice provision on growth performance, rumen fermentation, and behavior of dairy calves fed texturized starters. Forty-eight Holstein calves (42 ± 3 kg of body weight) were randomly assigned (n = 12 calves per treatment) in a 2 × 2 factorial arrangement of treatments with the factors of forage source [alfalfa hay (AH) and wheat straw (WS)] and forage PS [(AH: medium = 1.96 mm or long = 3.93 mm) and (WS: medium = 2.03 mm or long = 4.10 mm), as geometric mean diameters]. The treatments were (1) AH with medium PS (AH-MPS), (2) AH with long PS (AH-LPS), (3) WS with medium PS (WS-MPS), and (4) WS with long PS (WS-LPS). Regardless of forage PS, the preweaning starter intake, dry matter intake, metabolizable energy intake, weaning body weight, and forage intake were greater for AH calves than WS calves. Average daily gain, average daily gain/metabolizable energy intake, feed efficiency, and final body weight of the calves did not differ among groups. An interaction of forage source and forage PS influenced acetate, propionate, and acetate-to-propionate ratio in the rumen on d 35, with the greatest acetate proportion and acetate-to-propionate ratio, but the least propionate proportion for AH-MPS calves than the other calves. The total volatile fatty acid concentration and the rumen proportions of propionate (d 70), butyrate (d 35), and valerate (d 35) were greater in AH-MPS calves than in AH-LPS calves. Calves fed AH had greater total volatile fatty acid concentration (d 35 and 70) and propionate proportion (d 70), but lesser ruminal proportions of butyrate (d 35 and 70), valerate (d 35 and 70), and acetate-to-propionate ratio (d 70) compared with calves fed WS. The ruminal valerate proportion (d 70) was greatest in WS-MPS calves than the other calves. An interaction of forage source and forage PS influenced preweaning standing time and starter eating time, with the least standing time for WS-MPS calves and the greatest eating starter time for AH-LPS calves. Calves fed AH spent less time for rumination, but devoted more time to non-nutritive oral behaviors than WS calves. Calves fed forage with long PS spent more time for rumination, eating forage, and spent less time lying and non-nutritive oral behaviors than medium PS. In conclusion, forage source and PS interacted, affecting behavior and rumen fermentation when calves were fed texturized starters. In addition, a desirable ruminal pH in dairy calves can be obtained with texturized starters.

Effects of preweaning total plane of milk intake and weaning age on intake, growth performance, and blood metabolites of dairy calves.

The objective of this study was to evaluate the effects of preweaning total plane of milk intake and weaning age on intake, growth performance, and blood metabolites of dairy calves. A total of 48 Holstein calves (40 ± 1.6 kg of body weight) were used in a 2 × 2 factorial arrangement with the factors of weaning age (d 60 vs. 75) and the total plane of milk intake (medium vs. high) during the preweaning period. Calves were assigned to 1 of 4 treatments: (1) calves fed medium plane of milk (MPM) intake and weaned on d 60 of age (MPM-60d, 4 L/d of milk from d 3 to 10, 6 L/d of milk from d 11 to 55, and 3 L/d of milk from d 56 to 60 of age; total milk intake = 317 L), (2) calves fed MPM intake and weaned on d 75 of age (MPM-75d, 4 L/d of milk from d 3 to 10 and 4.5 L/d of milk from d 11 to 70 of age followed by feeding 2.25 L/d of milk from d 71 to 75 of age; total milk intake = 313 L), (3) calves fed high plane of milk (HPM) intake and weaned on d 60 of age (HPM-60d, 4 L/d of milk from d 3 to 10, 6 L/d of milk from d 11 to 20, and 8.5 L/d of milk from d 21 to 55 followed by feeding 4.25 L/d of milk from d 56 to 60 of age; total milk intake = ∼411 L); and (4) calves fed HPM intake and weaned on d 75 (HPM-75d, 4 L/d of milk from d 3 to 10, and 6 L/d of milk from d 11 to 70 of age followed by feeding 3 L/d of milk from d 71 to 75 of age; total milk intake = 407 L) with no milk refusals. All of the calves were monitored up to d 90 of age. Regardless of weaning age, starter feed intake and dry matter intake (% of body weight) were lower in calves fed HPM compared with those receiving MPM. A tendency for the plane of milk intake × weaning age interaction was observed for metabolizable energy intake with the highest value was recorded with the HPM-75d calves. The lowest efficiency of metabolizable energy intake and average feed efficiency was observed in HPM-60d calves throughout the experimental period as compared with the other groups. An interaction was found between the total plane of milk intake and weaning age regarding effects on total average daily gain, average daily gain/metabolizable energy intake, feed efficiency, final body weight, and plasma ß-hydroxybutyrate levels with the highest values measured in HPM-75d calves. Weaning on d 75 versus d 60 improved wither height and hip width, which tended to increase body length at the end of the trial. The results suggest that calves fed high amounts of milk during their preweaning period benefit from extending the time of weaning from 60 to 75 d of age based on average daily gain, feed efficiency, and final body weight.

Effects of forage provision to dairy calves on growth performance and rumen fermentation: A meta-analysis and meta-regression.

A meta-analysis of the potential effect of forage provision on growth performance and rumen fermentation of dairy calves was conducted using published data from the literature (1998-2016). Meta-regression was used to evaluate the effects of different forage levels, forage sources, forage offering methods, physical forms of starter, and grain sources on the heterogeneity of the results. We considered 27 studies that reported the effects of forage provision to dairy calves. Estimated effect sizes of forage were calculated on starter feed intake, average daily gain (ADG), feed efficiency (FE), body weight (BW), and rumen fermentation parameters. Intake of starter feed, ADG, BW, ruminal pH, and rumen molar proportion of acetate increased when supplementing forage but FE decreased. Heterogeneity (the amount of variation among studies) was significant for intake of starter feed, ADG, FE, final BW, and rumen fermentation parameters. Improving overall starter feed intake was greater in calves offered alfalfa hay compared with those offered other types of forages. During the milk feeding and overall periods, improving ADG was greater for calves fed a high level of forage (>10% in dry matter) compared with those fed a low level of forage (≤10% in dry matter) diets. The advantages reported in weight gain at a high level of forage could be due to increased gut fill. Improving overall ADG was lower for calves offered forages with textured starter feed compared with ground starter feed. The meta-regression analysis revealed that changes associated with forage provision affect FE differently for various forage sources and forage offering methods during the milk-feeding period. Forage sources also modulated the effect of feeding forage on ruminal pH during the milk-feeding period. In conclusion, forage has the potential to affect starter feed intake and performance of dairy calves, but its effects depend on source, level, and method of forage feeding and physical form of starter feed independently of grain sources included in the starter feed.

Growth performance, feeding behavior, and selected blood metabolites of Holstein dairy calves fed restricted amounts of milk: No interactions between sources of finely ground grain and forage provision.

The objective of this study was to investigate the effects of grain sources and forage provision on growth performance, blood metabolites, and feeding behaviors of dairy calves. Sixty 3-d-old Holstein dairy calves (42.2 ± 2.5 kg of body weight) were used in a 2 × 3 factorial arrangement with the factors being grain sources (barley and corn) and forage provision (no forage, alfalfa hay, and corn silage). Individually housed calves were randomly assigned (n = 10 calves per treatment: 5 males and 5 females) to 6 treatments: (1) barley grain (BG) without forage supplement, (2) BG with alfalfa hay (AH) supplementation, (3) BG with corn silage (CS) supplementation, (4) corn grain (CG) without forage supplement, (5) CG with AH supplementation, and (6) CG with CS supplementation. All calves had ad libitum access to water and starter feed throughout the experiment. All calves were weaned on d 49 and remained in the study until d 63. Starter feed intake and average daily gain (ADG) was greater for calves fed barley than those fed corn during the preweaning and overall periods. Calves supplemented with CS had greater final body weight and postweaning as well as overall starter feed intake than AH and non-forage-supplemented calves. During the preweaning and overall periods, feeding of CS was found to increase ADG compared with feeding AH and nonforage diets. However, feed efficiency was not affected by dietary treatments. Calves supplemented with CS spent more time ruminating compared with AH and control groups; nonnutritive oral behaviors were the greatest in non-forage-supplemented calves. Regardless of the grain sources, the rumen pH value was greater for AH calves compared with CS and non-forage-supplemented calves. Blood concentration of BHB was greater for CS-supplemented calves compared with AH and non-forage-supplemented calves. Furthermore, body length and heart girth were greater for calves fed barley compared with those fed corn, and also in forage-supplemented calves compared with non-forage-supplemented calves. These results showed no interactions between grain sources and forage provision on calf performance; however, the inclusion of CS and barley in starter diets could enhance the growth performance of Holstein calves during the transition from liquid to solid feed.

Long-term results of tension-free vaginal tape and pubovaginal sling in the treatment of stress urinary incontinence in female patients.

OBJECTIVES: To report the long-term outcome of tension-free vaginal tape (TVT) and pubovaginal sling (PVS) in the treatment of stress urinary incontinence (SUI) in female patients. MATERIALS AND METHODS: The long-term objective and subjective results of female patients who were previously randomized in a single blind study to two arms, TVT or PVS, between 2000 and 2004, were evaluated. The patients were asked if they were satisfied with the results of the procedure and if they would recommend it to a friend or relative. The assessment included a physical examination and cough-induced stress test. Satisfaction levels were assessed by Likert-type scale. Cure was described as absence of urine leakage in any circumstances, while improvement was characterized as subjective improvement of SUI without complete resolution. RESULTS: One hundred women with SUI underwent surgery at the present medical center between 2000 and 2004. A total of 52 patients were followed clinically for objective and subjective assessment. Seventeen were interviewed only by telephone. The objective cure rate was 81.5% and 84%, where as subjective cure rate was 70.3% and 71.9%, for TVT versus PVS, respectively (p > 0.05). After an average follow-up of 10.5 years, there was no difference in clinical outcome, satisfaction scores, and postoperative complications between the two groups. CONCLUSION: Both TVT and PVS are safe and effective treatments for SUI in fe- male patients, with acceptable success rate in long term follow-up.

Effects of forage offering method on performance, rumen fermentation, nutrient digestibility and nutritional behaviour in Holstein dairy calves.

The potential effect of dietary forage supplementation on the performance and rumen development in dairy calves is well established. However, limited research has been directed to the comparative effects of forage offering methods on calf performance. The objective of the present study was to determine the effects of forage provision methods (total mixed ration or free choice) on the performance, nutrient digestibility, rumen fermentation and nutritional behaviour in newborn calves. Forty-five Holstein dairy calves (3 days of age and 41 ± 2 kg of body weight) were assigned to the following three groups (n = 15): (i) starter without forage provision (CON), (ii) starter supplemented with 10% alfalfa hay (AH) as a total mixed ration (AH-TMR) and (iii) starter and AH as a free-choice provision (AH-FC) for a period of 70 days. All the calves were offered 5 l of milk/day from day 3 to 50, and 2.5 l/day from day 50 until weaning on day 56. Dry matter intake (DMI) was greater (p < 0.01) in the AH-TMR and AH-FC treatments than in the CON during the pre- and post-weaning periods. Calves fed the AH-FC diet showed the highest post-weaning DMI among the treatments. The calves receiving ad libitum forage tended (p = 0.08) to increase crude protein digestibility and overall volatile fatty acids (VFA) concentrations in the rumen. No differences were observed among the treatments at the time spent on standing, lying, eating and performing non-nutritive oral behaviours. Compared to CON calves, animals in the AH-TMR treatment spent more time (p < 0.05) ruminating. In conclusion, our data suggest that forage supplementation in both forage offering methods increased total DMI, ruminal pH and ruminating time in dairy calves. Hence, there is no benefit in the free-choice provision of AH in dairy calves.