Ethmoidal and maxillary nerve block versus systemic opioid administration during rhinoscopy in dogs: a non-randomised clinical trial.

OBJECTIVES: This study aimed to evaluate the clinical effects of ethmoidal and maxillary nerve blocks during rhinoscopy in dogs. MATERIALS AND METHODS: Fourteen dogs underwent rhinoscopy. Under general anaesthesia with isoflurane, ethmoidal and maxillary nerve blocks were applied bilaterally using 2% lidocaine before rhinoscopy in eight dogs (EM group). Six dogs were premedicated with hydromorphone (0.05 mg/kg) as a substitute for local nerve block (H group). During rhinoscopy, the heart rate, arterial blood pressure and end-tidal isoflurane concentration were recorded. The vaporizer setting was adjusted to increase the end-tidal isoflurane concentration when reflex movement was caused by nasal stimulation. RESULTS: The H group, compared to the EM group, had an increase in HR that was 18 beats/minute (95% CI: 11 to 26) higher, an increase in SAP that was 22 mmHg (12 to 31) higher, an increase in MAP that was 15 mmHg (7 to 23) higher, an increase in DAP that was 12 mmHg (5 to 19) higher, and an increase in end-tidal isoflurane concentration that was 0.4% (0.3 to 0.5) higher. Head movement due to endoscope insertion was observed in 5/6 dogs (83.3%) in the H group and 1/8 dogs (12.5%) in the EM group (odds ratio, 0.029; ra95% CI, 0.001-0.574). CLINICAL SIGNIFICANCE: Compared with administration of 0.05 mg/kg hydromorphone, concurrent block of the ethmoidal and maxillary nerves can reduce the cardiovascular response, reflex movement and anaesthetic requirement during rhinoscopy in dogs.

Transient postoperative glycosuria after isoflurane exposure in two dogs.

The present report describes two surgical cases involving the development of sudden glycosuria after isoflurane anaesthesia, despite the dogs having normal blood glucose levels and renal glucose reabsorption. The glycosuria manifested 1 day after surgery and resolved spontaneously within 2 days in both cases. Considering that the surgeries (subcutaneous mandibular mass removal and fracture repair) were unrelated to the kidneys, and there were no remarkable events during anaesthesia, the glycosuria may have been associated with the isoflurane anaesthesia. There have been several previous reports of glycosuria in human patients following transient proximal tubule dysfunction due to volatile anaesthetics. This case report suggests the possibility of transient renal dysfunction following isoflurane anaesthesia in these two clinically healthy dogs. However, considering the observational nature of this report, it can not be excluded that any other procedure performed in these animals was responsible of the observed glycosuria.

ICSI outcomes using testicular spermatozoa in non-azoospermic couples with recurrent ICSI failure and no previous live births.

BACKGROUND: The use of testicular over ejaculated spermatozoa for ICSI has been presented as an alternative to overcome infertility in men with poor semen parameters or high levels of sperm DNA fragmentation. OBJECTIVE: To evaluate the efficacy of testicular ICSI outcomes in couples with no previous live birth and recurrent ICSI failure using ejaculated spermatozoa by comparison to the outcomes of couples with similar history of recurrent ICSI using ejaculated spermatozoa only. MATERIALS AND METHODS: A total of 145 couples undergoing ejaculated or testicular ICSI cycles with no previous live births and with at least two previous failed ICSI cycles with ejaculated spermatozoa were evaluated retrospectively. ICSI was performed either with ejaculated (E-ICSI) or with testicular (T-ICSI) spermatozoa. Semen parameters and sperm DNA quality were assessed prior to the oocyte collection day. Primary outcomes included cumulative live birth and pregnancy rates. Secondary analysis included percentage of DNA fragmentation in ejaculated spermatozoa (SCSA® and TUNEL). RESULTS: Patients undergoing T-ICSI (n = 77) had a significantly higher clinical pregnancy rate/fresh embryo transfer (ET) (27.9%; 17/61) and cumulative live birth rate (23.4%; 15/64) compared to patients using E-ICSI (n = 68) (clinical pregnancy rate/fresh ET: 10%; 6/60 and cumulative live birth rate: 11.4%; 7/61). Further, T-ICSI yield significantly better cumulative live birth rates than E-ICSI for men with high TUNEL (≥36%) (T-ICSI: 20%; 3/15 vs. E-ICSI: 0%; 0/7, p < 0.025), high SCSA® (≥25%) scores (T-ICSI: 21.7%; 5/23 vs. E-ICSI: 9.1%; 1/11, p < 0.01), or abnormal semen parameters (T-ICSI: 28%; 7/25 vs. E-ICSI: 6.7%; 1/15, p < 0.01). CONCLUSIONS: The use of testicular spermatozoa for ICSI in non-azoospermic couples with no previous live births, recurrent ICSI failure, and high sperm DNA fragmentation yields significantly better live birth outcomes than a separate cohort of couples with similar history of ICSI failure entering a new ICSI cycle with ejaculated spermatozoa.

Do trained reproductive endocrinologists perform better than their trainees? Comparing clinical pregnancy rates and live birth rates after transfer of single fresh blastocysts.

PURPOSE: To compare clinical pregnancy rates and live birth rates of single blastocyst transfers performed by attending physicians or fellows in reproductive endocrinology and infertility program. METHODS: Retrospective study in an academic reproductive center. We evaluated 932 fresh single blastocyst transfer cycles performed by fellows in training (389 embryo transfers) and by attending physicians (543 embryo transfers). RESULTS: There were no differences in the baseline characteristics and IVF cycle parameters between patients who had transfers performed by fellows or attending physicians. Transfers performed by attending physicians or fellows resulted in similar CPR (46.5 vs. 42.9%, p = 0.28) and LBR (38.3 vs. 34.2%, p = 0.11). Multivariate logistic regression analysis showed that even after adjusting for possible confounders (age, gravity, parity, baseline FSH, antral follicle count, dose of gonadotropins, stimulation protocol, and quality of embryo transferred), CPR (OR 0.81, CI 0.62-1.07) and LBR (OR 0.79, CI 0.6-1.05) in the two groups were comparable. CONCLUSION: Clinical pregnancy rate and live birth rate after embryo transfer performed by attending staffs or fellows are comparable. This finding reassures fellowship programs that allowing fellows to perform embryo transfers does not compromise the outcome.

Does using testicular sperm retrieval rather than ejaculated spermatozoa improve reproductive outcomes in couples with previous ART failure and poor ovarian response? A case-controlled study.

The objective of this study was to assess whether testicular-retrieved spermatozoa improve reproductive outcomes compared to fresh ejaculate in women with poor ovarian response and a history of previous ART failure. The study was performed as a retrospective case-control study at a university-based reproductive center in Montreal, Quebec, Canada. Eighteen poor-responder patients were matched 3 : 1 with 54 controls. Poor responders were defined as those with ≤3 oocytes retrieved at oocyte pickup. Cases were identified as poor responders, and only those with previous IVF failure(s) as an indication for testicular-retrieved spermatozoa were included. Controls were age and cycle attempt number matched. All patients were included only once. From January 1, 2009 to December 31, 2015, all patients and controls underwent an IVF cycle using ICSI with either testicular spermatozoa or ejaculated spermatozoa, respectively. Outcomes included live birth rate, pregnancy rate, miscarriage rate, oocyte number, and embryo transfer (ET) day. The results showed live birth rates, pregnancy rates, and miscarriage rates were similar. There were fewer day 2 ETs (8.5% vs. 48.6%, p = 0.01) and more day 5 blastocyst transfers (25.0% vs. 5.4%, p = 0.05) in the testicular sperm retrieval group compared to controls and thus an overall suggestion of better embryo quality in the testicular sperm group. Overall, however, the use of testicular sperm retrieval appears to add little. Women with poor ovarian response typically have a poor prognosis with respect to live birth rates, and this is further supported in this study. The suggestion of better embryo quality in the testicular-retrieved sperm group would need to be further assessed in a larger multicentered study.

Expression of the glutamine metabolism-related proteins glutaminase 1 and glutamate dehydrogenase in canine mammary tumours.

Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumour growth and glutamine metabolism. Because of their similarities, canine mammary carcinomas are useful for studying human breast cancer. Accordingly, we investigated the correlations between the expression of glutamine metabolism-related proteins and the pathological features of canine mammary tumours. We performed immunohistochemical and western blot analysis of 39 mammary tumour tissues. In immunohistochemical analysis, the expression of glutaminase 1 (GLS1) in the epithelial region increased according to the histological grade (P < .005). In the stromal region, complex-type tumours displayed significantly higher GLS1 intensity than simple-type tumours. However, glutamate dehydrogenase expression did not show the same tendencies as GLS1. The western blot results were consistent with the immunohistochemical findings. These results suggest that the expression of GLS1 is correlates with clinicopathological factors in canine mammary tumours and shows a similar pattern to human breast cancer.

Morphometric analysis of the maxillary root apex positions according to crowding severity.

OBJECTIVES: To determine differences in arch forms derived from the root apices locations between individuals with <2 mm maxillary crowding and controls. SETTING AND SAMPLE POPULATION: The Department of Orthodontics, Pusan National University. Cone-beam computed tomography (CBCT) images of 102 patients in the control group and 95 patients in the crowding group. MATERIALS AND METHODS: X, Y and Z coordinates of the tip of the crowns and the apex of the root of the maxillary teeth (except second molars) were determined on the CBCT images. The acquired three-dimensional (3D) coordinates were converted into two-dimensional (2D) coordinates via projection on the palatal plane, and the Procrustes analysis was employed to process the converted 2D coordinates. The mean shape of the arch form derived from the location of the tip of the crowns and the apex of the root was compared between groups using the statistical shape analysis. RESULTS: There was a statistically significant difference (P = .046) between the groups for the mean shape of the root apex arch form, but the difference was small and clinically irrelevant as it is minor compared to the degree of crowding. CONCLUSIONS: Maxillary arch from at the level of the maxillary apices only shows minor differences between crowded and non-crowded dentitions.

The relationship between fat and progesterone, estradiol, and chorionic gonadotropin levels in Quebec cow's milk.

PURPOSE: The majority of milk in industrialized countries is obtained from pregnant cows, which contains increased levels of estrogen and progesterone compared to non-pregnant cows. The aim of this study was to quantify the amount of hormones present in milk with different fat content because previous studies on humans have shown potential effects of increased milk consumption on serum and urine hormone levels as well as on sperm parameters. However, it is unclear whether consumption of milk at the currently recommended levels would lead to systemic effects. METHODS: Samples of cow's milk of varying fat concentrations (0, 1, 2, 3.25, 10, and 35%) were analyzed via competitive ELISA assays. RESULTS: Progesterone concentrations were significantly correlated to increasing fat content of milk (r = 0.8251, p = 0.04). CONCLUSIONS: Research on conditions in which additional progesterone may have an effect on human health should consider inclusion of limitation of milk intake and its effects. Further studies are needed to determine the concentration of progesterone in milk of different fat content in other regions and countries and to quantify the potential pathophysiologic role.

Do statins adversely affect the HbA1c of diabetic patients?

This paper discusses the adverse effect of statins on the HbA1c levels of diabetic patients. Studies have shown that statins may slightly worsen the HbA1c level. The effects vary depending on the type of statins, the dosage and the duration of therapy. However, it has been confirmed that statin use has benefits that outweigh its harms. Therefore, a diabetic patient should be given advice on the need for appropriate lifestyle changes and the importance of continuing the statins.

Theoretical rationalization of the singlet-triplet gap in OLEDs materials: impact of charge-transfer character.

New materials for OLED applications with low singlet-triplet energy splitting have been recently synthesized in order to allow for the conversion of triplet into singlet excitons (emitting light) via a Thermally Activated Delayed Fluorescence (TADF) process, which involves excited-states with a non-negligible amount of Charge-Transfer (CT). The accurate modeling of these states with Time-Dependent Density Functional Theory (TD-DFT), the most used method so far because of the favorable trade-off between accuracy and computational cost, is however particularly challenging. We carefully address this issue here by considering materials with small (high) singlet-triplet gap acting as emitter (host) in OLEDs and by comparing the accuracy of TD-DFT and the corresponding Tamm-Dancoff Approximation (TDA), which is found to greatly reduce error bars with respect to experiments thanks to better estimates for the lowest singlet-triplet transition. Finally, we quantitatively correlate the singlet-triplet splitting values with the extent of CT, using for it a simple metric extracted from calculations with double-hybrid functionals, that might be applied in further molecular engineering studies.

Cost-Effective Force Field Tailored for Solid-Phase Simulations of OLED Materials.

A united atom force field is empirically derived by minimizing the difference between experimental and simulated crystal cells and melting temperatures for eight compounds representative of organic electronic materials used in OLEDs and other devices: biphenyl, carbazole, fluorene, 9,9'-(1,3-phenylene)bis(9H-carbazole)-1,3-bis(N-carbazolyl)benzene (mCP), 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (pCBP), phenazine, phenylcarbazole, and triphenylamine. The force field is verified against dispersion-corrected DFT calculations and shown to also successfully reproduce the crystal structure for two larger compounds employed as hosts in phosphorescent and thermally activated delayed fluorescence OLEDs: N,N'-di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPD), and 1,3,5-tri(1-phenyl-1H-benzo[d]imidazol-2-yl)phenyl (TPBI). The good performances of the force field coupled to the large computational savings granted by the united atom approximation make it an ideal choice for the simulation of the morphology of emissive layers for OLED materials in crystalline or glassy phases.

Fentanyl-induced asystole in two dogs.

Fentanyl is used in small animals for perioperative analgesia during anaesthesia. Severe bradycardia and asystole were observed on bolus administration of a 3 µg/kg loading dose of fentanyl in two dogs under isoflurane anaesthesia. Premedication with 10 µg/kg glycopyrrolate did not prevent asystole in the first case; and although bradycardia was treated with 5 µg/kg glycopyrrolate administered intravenously in the second case, the heart rate continuously decreased and asystole subsequently developed. Asystole in both cases was quickly corrected by intravenous administration of 0 · 04 mg/kg atropine and closed chest compressions. This case report describes asystole induced by fentanyl administration in isoflurane anaesthetised dogs. Atropine was more effective than glycopyrrolate in the treatment of fentanyl-induced asystole.

Characterization of urinary CD4⁺ and CD8⁺ T cells in kidney transplantation patients with polyomavirus BK infection and allograft rejection.

BACKGROUND AND OBJECTIVES: The objective of this study was to characterize CD4(+) and CD8(+) T-cell populations in blood and urine of renal transplant patients with BK virus (BKV) infection or allograft rejection. MATERIALS AND METHODS: Percentages and absolute numbers of CD4(+) and CD8(+) effector memory T-cell subtype (TEM ) and terminal differentiated T cells (TTD ) in renal transplant patients with BKV infection (n = 14), with an episode of allograft rejection (n = 9), and in uncomplicated renal transplant patients with a stable kidney function (n = 12) were measured and compared using 4-color fluorescence-activated cell sorting. Results were correlated with the number of CD4(+) and CD8(+) T cells in renal biopsies. RESULTS: In patients with allograft rejection, the number of urinary CD4(+) TEM and CD8(+) TEM cells was significantly increased compared to patients with BKV infection or patients without complications. Positive correlation was found between the number of CD4(+) and CD8(+) cells in the renal biopsies and the number of CD4(+) and CD8(+) cells in urine. In patients with rejection, after 2 months of immunosuppressive therapy, a reduction in urinary CD8(+) TEM cells was found. CONCLUSIONS: CD4(+) TEM and CD8(+) TEM cells in urine could be a marker to distinguish allograft rejection from BKV-associated nephropathy and to monitor therapy effectiveness in renal transplant patients with allograft rejection.

Electroporation markedly improves Sleeping Beauty transposon-induced tumorigenesis in mice.

The Sleeping Beauty (SB) transposon system is an important tool for genetic studies. It is used to insert a gene of interest into the host chromosome, thus enabling permanent gene expression. However, this system is less useful in higher eukaryotes because the transposition frequency is low. Efforts to improve the efficacy of the SB transposon system have focused on the method of gene delivery, but although electroporation has recently attracted much attention as an in vivo gene delivery tool, the simultaneous use of electroporation and the SB transposon system has not been studied for gene transfer in mice. In this study, electroporation was used in a model of SB transposon-induced insertional tumorigenesis. Electroporation increased the rate of tumor development to three times that of the control group. There was no difference in phenotype between tumors induced with the SB transposon system alone and those induced by the SB transposon and electroporation. Electroporation therefore may be an efficient means of improving the efficacy of gene transfer via the SB transposon system.

Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation.

Acyloxydiene-Fe(CO)3 complexes can act as enzyme-triggered CO-releasing molecules (ET-CORMs). Their biological activity strongly depends on the mother compound from which they are derived, i.e. cyclohexenone or cyclohexanedione, and on the position of the ester functionality they harbour. The present study addresses if the latter characteristic affects CO release, if cytotoxicity of ET-CORMs is mediated through iron release or inhibition of cell respiration and to what extent cyclohexenone and cyclohexanedione derived ET-CORMs differ in their ability to counteract TNF-α mediated inflammation. Irrespective of the formulation (DMSO or cyclodextrin), toxicity in HUVEC was significantly higher for ET-CORMs bearing the ester functionality at the outer (rac-4), as compared to the inner (rac-1) position of the cyclohexenone moiety. This was paralleled by an increased CO release from the former ET-CORM. Toxicity was not mediated via iron as EC50 values for rac-4 were significantly lower than for FeCl2 or FeCl3 and were not influenced by iron chelation. ATP depletion preceded toxicity suggesting impaired cell respiration as putative cause for cell death. In long-term HUVEC cultures inhibition of VCAM-1 expression by rac-1 waned in time, while for the cyclohexanedione derived rac-8 inhibition seems to increase. NFκB was inhibited by both rac-1 and rac-8 independent of IκBα degradation. Both ET-CORMs activated Nrf-2 and consequently induced the expression of HO-1. This study further provides a rational framework for designing acyloxydiene-Fe(CO)3 complexes as ET-CORMs with differential CO release and biological activities. We also provide a better understanding of how these complexes affect cell-biology in mechanistic terms.

Helicobacter canis bacteremia in a renal transplant patient.

Here we present a case report of a 41-year-old woman suffering from high fever and bacteremia due to Helicobacter canis, 11 months after kidney transplantation. Identification of H. canis was achieved by 16s rDNA sequence analysis of a positive blood culture. The patient was restored fully to health after antibiotics therapy (cefuroxime and ciprofloxacin). Until now, only 4 human clinical cases have been described with H. canis bacteremia. This study describes for the first time, to our knowledge, an infection with H. canis in a kidney transplant patient.

Complement mediated renal inflammation induced by donor brain death: role of renal C5a-C5aR interaction.

Kidneys retrieved from brain-dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complement contributes to allograft injury remains to be elucidated. The aim of this study was to investigate systemic C5a release after BD in human donors and direct effects of C5a on human renal tissue. C5a levels were measured in plasma from living and brain-dead donors. Renal C5aR gene and protein expression in living and brain-dead donors was investigated in renal pretransplantation biopsies. The direct effect of C5a on human renal tissue was investigated by stimulating human kidney slices with C5a using a newly developed precision-cut method. Elevated C5a levels were found in plasma from brain-dead donors in concert with induced C5aR expression in donor kidney biopsies. Exposure of precision-cut human kidney slices to C5a induced gene expression of pro-inflammatory cytokines IL-1 beta, IL-6 and IL-8. In conclusion, these findings suggest that systemic generation of C5a mediates renal inflammation in brain-dead donor grafts via tubular C5a-C5aR interaction. This study also introduces a novel in vitro technique to analyze renal cells in their biological environment.

Treatment of steroid-resistant acute renal allograft rejection with alemtuzumab.

Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (15-30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5-4.0 mg/kg bodyweight i.v. for 10-14 days; n = 20). We assessed treatment-failure (graft loss, lack of improvement of graft function or need for additional anti-rejection treatment), infections during the first 3 months after treatment and infusion-related side effects. In both groups, the median time-interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff-IIA or higher. Three alemtuzumab-treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion-related side-effects in three alemtuzumab-treated patients (27%), and more severe infusion-related side effects in 17 RATG-treated patients (85%, p = 0.013). Drug related costs of alemtuzumab-treatment were lower than of RATG-treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid-resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion-related side-effects. These data warrant a prospective trial.

Cone-beam computed tomography evaluation of short- and long-term airway change and stability after orthognathic surgery in patients with Class III skeletal deformities: bimaxillary surgery and mandibular setback surgery.

The purpose of this study was to evaluate the volumetric change of the upper airway space in 36 Class III patients who had undergone bimaxillary surgery or isolated mandibular setback, and, further, to analyse the relation between post-surgical stability and airway change using cone-beam computed tomography (CBCT). A three-dimensional (3D) CBCT examination was performed at three stages: T0 (before surgery), T1 (an average of 4.6 months after surgery), and T2 (an average of 1.4 years after surgery). The results showed that the volumes of the oropharyngeal and hypopharyngeal airways decreased significantly 4.6 months post-surgery in the mandibular setback group (p<0.05), and these diminished airways had not recovered 1.4 years post-surgery. In the bimaxillary surgery group, the volume of the oropharyngeal airway also decreased. A Spearman correlation analysis showed that the anteroposterior length of the hypopharyngeal area had a correlation with post-surgical stability in the isolated mandibular surgery group, and that the cross-sectional area of the nasopharynx was correlated with maxillary relapse only in the bimaxillary surgery group (p<0.05).

Obstetric outcomes of IVF trichorionic triamniotic triplets which are spontaneously or electively reduced to twins.

PURPOSE: To assess the obstetric outcome of IVF triplets which are spontaneously or electively reduced to twins. METHODS: Retrospective study of trichorionic triplets (TT) and dichorionic twins (DT) conceived with IVF. RESULTS: Compared to TT without reduction, TT with spontaneous reduction (SR) (OR: 5.6, 95% CI: 1.6-19.9) or elective reduction (ER) (OR: 14.0, 95% CI: 3.92-50.02) to twins were significantly more likely to be delivered at ≥34 weeks. Compared to DT likelihood of delivery ≥34 weeks was similar for SR and ER. Compared to TT without reduction, the risk of pregnancy loss before 24 weeks was not increased with SR or ER. Compared to DT the risk of pregnancy loss before 24 weeks was not significantly increased for SR or ER. CONCLUSION: Obstetric outcome of IVF triplets with SR is better than ongoing triplets and is similar to that of ER of TT and DT.