A highlight on carbamazepine-induced adverse drug reactions in Saudi Arabia: a retrospective medical records-based study.

The link between human leukocyte antigen (HLA) alleles and carbamazepine-induced cutaneous, respiratory, and gastrointestinal adverse drug reactions (ADR) has created a window of opportunity for preventing certain forms of cutaneous adverse drug reactions (cADRs); however, there is not enough data to make pharmacogenomic recommendations that can be implemented globally. The aim of this study is to assess and document carbamazepine-induced adverse reactions among prescribed Saudi/non-Saudi patients. A retrospective chart review was performed for patients who received carbamazepine (CBZ) in the period between 2016 and 2020, in the Kingdom of Saudi Arabia. Data were gathered and descriptive statistical analyses were performed on the data for the study sample. Comparisons were made using the chi-square test or independent samples' t-test. Statistical significance was considered at p < .05. All statistical analyses were performed using IBM SPSS 21.0 (Armonk, NY; IBM Corp). Results from multivariate logistic regression analyses showed that higher likelihood of carbamazepine-induced adverse reactions was significantly associated with younger age, OR = 0.82, 95% CI (0.74, 0.90); p < 0.001. Patients who were prescribed CBZ for reasons other than epilepsy or seizures were significantly more likely to develop carbamazepine-induced adverse reactions (epilepsy vs. other; OR = 0.63, p = 0.013; seizures vs. other; OR = 0.59, p = 0.018). Gender or medication duration were not related to carbamazepine-induced adverse reactions (p > 0.05). The findings of this study are comparable with those of other studies assessing carbamazepine-associated adverse reactions in children and adults. Recommendations include genetic prescreening, educating patients and parents on the possibility of adverse reactions, and routine laboratory monitoring.

The current practice of using angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in diabetic hypertensive and non-hypertensive patients. Is there a room for vitamin D?

OBJECTIVES: To determine the current pattern of using angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in diabetic nephropathy (DN), and assess physician awareness of using vitamin D in the prevention and treatment of DN. METHODS: A cross-sectional study implementing a validated questionnaire, which was distributed to physicians in the aforementioned specialties in 3 hospitals in Saudi Arabia (Almanee Hospital, King Saud Medical City [KSMC], and Riyadh Care Hospital [RCH]) between April 2019 and November 2019. We used IBM SPSS 26.0 to perform descriptive statistical analyses and comparisons were based on the Chi-square test. RESULTS: Forty-one physicians (30%) reported the use of combination therapy of ACEi and ARBs. Fifty-six (41%) physicians reported that they never used vitamin D in the treatment of DN, and 48% agreed that vitamin D can benefit patients with DN. 52% of the respondents reported the existence of guidelines. The vast majority (94%) recommended clearer guidelines on monitoring renal function in patients treated with ACEi or ARBs. CONCLUSION: There is a universal agreement among physicians regarding the use of ACEi and ARBs for the treatment of DN with limited awareness of the bene ts of using vitamin D. Hence, the development of specific guidelines for its use are recommended.

Twofold Porosity and Surface Functionalization Effect on Pt-Porous GaN for High-Performance H2-Gas Sensors at Room Temperature.

The achievement of H2 detection, up to 25 ppm, at room temperature using sulfur-treated, platinum (Pt)-decorated porous GaN is reported in this study. This achievement is attributed to the large lateral pore size, Pt catalyst, and surface treatment using organic sulfide. The performance of H2-gas sensors is studied as a function of the operating temperature by providing an adsorption activation energy of 22 meV at 30 ppm H2, confirming the higher sensitivity of the sulfide-treated Pt-porous GaN sensor. Furthermore, the sensing response of the sulfide-treated Pt-porous GaN gas sensor increases with the increase in porosity (surface-to-volume ratio) and pore radii. Using the Knudsen diffusion-surface reaction equation, the H2 gas concentration profile is simulated and fitted within the porous GaN layer, revealing that H2 diffusion is limited by small pore radii because of its low diffusion rate. The simulated gas sensor responses to H2 versus the pore diameter show the same trend as observed for the experimental data. The sulfide-treated Pt-porous GaN sensor achieves ultrasensitive H2 detection at room temperature for 125 nm pore radii.

Replacing Soybean Meal with Sesame Meal in the Diets of Lactating Awassi Ewes Suckling Single Lambs: Nutrient Digestibility, Milk Production, and Lamb Growth.

Two experiments were conducted to assess the influence of sesame meal (SM) feeding on nutrient digestibility, N balance, milk production and composition, ewes' body weight change, and growth performance of lambs. In experiment 1, 18 ewe lambs were randomly distributed into three diets to evaluate the effects of soybean meal replacement with SM on nutrient intake, digestibility, and N balance. Treatments were no SM (SM0), 7.5% SM (SM7.5), or 15% SM (SM15) of the dietary dry matter (DM). Aside from intake and digestibility of ether extract (EE), which was greater in the SM-containing diets compared with SM0, intake and digestibility of the remaining nutrients was similar among dietary treatments. In experiment 2, 30 ewes suckling single lambs were randomly assigned to the same diets used in experiment 1. Intakes of DM, crude protein, neutral detergent fiber, and acid detergent fiber were unaffected by treatment. Milk yield was greater in SM diets than in the SM0 diet. Cost/kg of milk production decreased while feed efficiency improved in the SM-diets compared to the SM0 diet. In conclusion, results of the current studies demonstrate the possibility of replacing soybean meal with sesame meal in diets of lactating Awassi ewes.

Flexible InGaN nanowire membranes for enhanced solar water splitting.

III-Nitride nanowires (NWs) have recently emerged as potential photoelectrodes for efficient solar hydrogen generation. While InGaN NWs epitaxy over silicon is required for high crystalline quality and economic production, it leads to the formation of the notorious silicon nitride insulating interface as well as low electrical conductivity which both impede excess charge carrier dynamics and overall device performance. We tackle this issue by developing, for the first time, a substrate-free InGaN NWs membrane photoanodes, through liftoff and transfer techniques, where excess charge carriers are efficiently extracted from the InGaN NWs through a proper ohmic contact formed with a high electrical conductivity metal stack membrane. As a result, compared to conventional InGaN NWs on silicon, the fabricated free-standing flexible membranes showed a 10-fold increase in the generated photocurrent as well as a 0.8 V cathodic shift in the onset potential. Through electrochemical impedance spectroscopy, accompanied with TEM-based analysis, we further demonstrated the detailed enhancement within excess charge carrier dynamics of the photoanode membranes. This novel configuration in photoelectrodes demonstrates a novel pathway for enhancing the performance of III-nitrides photoelectrodes to accelerate their commercialization for solar water splitting.

The effects of Saccharomyces cerevisiae supplementation on intake, nutrient digestibility, and rumen fluid pH in Awassi female lambs.

AIM: The aim of this study was to evaluate the effect of feeding low (LO)- or high (HI)-fiber diets supplemented with Saccharomyces cerevisiae (SC) on nutrient intake, digestibility, nitrogen balance, rumen fluid pH, and serum concentrations of glucose and urea nitrogen in Awassi female lambs in a 2×2 factorial arrangement of treatments. MATERIALS AND METHODS: Experimental diets were as follows: (1) LO-fiber diet with no SC supplementation (-LO), (2) LO-fiber diet supplemented with SC (+LO), (3) HI-fiber diet with no SC supplementation (-HI), or (4) HI-fiber diet supplemented with SC (+HI). Eight female lambs were used in a replicated 4×4 Latin square design with 15-day experimental periods (10-day adaptation period and 5-day collection period). RESULTS: A fiber×SC interaction (p≤0.05) was detected for dry matter (DM) and crude protein (CP) intake among diets showing greater DM and CP intake for +LO diet compared to +HI group supplemented with SC, whereas -LO and -HI were intermediate. A fiber×SC interaction (p=0.05) was also detected for the neutral detergent fiber (NDF) intake among diets. Intake of NDF was greater for the -HI diet compared with +LO and -LO diets. Similarly, NDF intake was greater for +HI diet than -LO diet. A tendency (p=0.07) for a fiber×SC interaction was detected for acid detergent fiber (ADF) intake among diets as well. ADF intake tended to be greater for HI-fiber diets. No difference was observed in the rumen fluid pH for lambs fed with the different diets. No fiber×SC interactions were detected for the digestibility of DM, CP, NDF, and ADF among dietary treatments. Digestibility of DM was greater (72.9 g/100 g vs. 67.1 g/100 g; p=0.0002) for LO versus HI fiber. However, NDF and ADF digestibilities were greater (60.8 and 61.9 g/100 g vs. 55.8 and 52.7 g/100 g for NDF and ADF digestibility, respectively; p≤0.01) for the HI-fiber than the LO-fiber diets. CONCLUSION: Results obtained in the current study indicate that SC supplementation has a minimal effect on the performance of Awassi female lambs fed with varying fiber levels.

Medical students' attitude toward anesthesia as a future career.

OBJECTIVES: The purpose of this study is to understand the attitude of medical students at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) toward anesthesia as a specialty and to determine common factors influencing their career choice options. STUDY DESIGN: This was a cross-sectional study. METHODS: The study was conducted between March 25, and April 20, 2017, at KSAU-HS. The survey was distributed among 5th and 6th years medical students. Data were collected through a validated hardcopy questionnaire of 16 multiple choice questions. The questionnaire included demographic characteristics, specialty preferences, what factors attract Saudi medical students to choose their preferred specialty and how they view the option of choosing anesthesiology as a career. RESULTS: A total of 236 students completed the questionnaire. The majority of respondents were in their 5th year of medical school representing (62%). The distribution of medical field interest ranged from (38%) surgery to (1%) anesthesiology. approximately, (60%) thought that controllable lifestyle was an important factor to consider in choosing a residency program. Only (45%) of respondents thought that prestige of specialty is a major factor that would influence their choice for a specialty. CONCLUSION: Based on the outcome of the study, it is recommended that medical undergraduate students exposure to anesthesia specialty should be magnified. Greater efforts have to be made to increase the number of medical students preferring anesthesia through emphasizing on the positive aspects of the specialty.

Validity and reliability of the Arabic version of the the EuroQOL (EQ-5D). A study from Saudi Arabia.

OBJECTIVES: The EuroQOL five-dimension questionnaire (EQ-5D) is one of the most widely used tools to evaluate health-related quality of life (HRQOL). Studies on the psychometric features of the EQ-5D in the Gulf region of the Middle East are lacking. This study is aimed at evaluating the validity and reliability of the Arabic version of the EQ-5D in Saudi Arabia. METHODS: The study was done utilizing a convenience sample of Arabic-speaking adult patients or visitors at the outpatient clinic at King Abdulaziz Medical City (KAMC) in Riyadh during October-December 2015. Participants were interviewed using translated into Arabic versions of the EQ-5D and the Short Form Health Survey (SF-36). Known-group construct validity of the EQ-5D and visual analog scale (EQ-VAS) was assessed through testing a number of hypotheses comparing responses to EQ-5D dimensions or EQ-VAS to SF-36 scores by dimension and external variables. Test-retest reliability was also assessed. RESULTS: Eighty subjects were included in the study. Mean ± standard deviartion age was 33.0 ± 11.6 years, with 51% of females. Responses to EQ-5D dimensions revealed that the proportion of respondents reporting problems ranged from 6% for problems with self-care to 48% for pain/discomfort. All of the five hypotheses linking EQ-5D responses to external variables were satisfied. Test-retest reliability was evaluated using Cohen's κ, which ranged from 0.53 to 1.00. CONCLUSION: Validity and reliability of the Arabic EQ-5D were established for evaluating HRQOL in Saudi Arabia. Further studies are warranted to evaluate the validity and reliability of this standard tool in other Arabic-speaking countries with varying cultures.

Acute Kidney Injury in Pediatric Treated with Vancomycin and Piperacillin-Tazobactam in Tertiary Care Hospital.

BACKGROUND: Vancomycin and piperacillin-tazobactam (PTZ) are commonly used as empirical therapy for patients with health care associated infections. Vancomycin has been recognized as a nephrotoxic agent and in a few cases in the literature PTZ has been associated with interstitial nephritis nevertheless; the combination of these agents has routinely been used for many years. However, there have been some observational studies that showed high rates of acute kidney injury (AKI) in patients receiving vancomycin and PTZ concomitant treatment compared to patients receiving vancomycin alone. The incidence of AKI in adult patients receiving vancomycin and PTZ concomitant treatment was reported in these studies to be relatively high. Similar studies in pediatric patients are lacking. METHOD: We conducted a single center retrospective chart review of 248 pediatric patients receiving one of the following treatments: vancomycin alone 36 patients, vancomycin/PTZ 62 patients, vancomycin/ceftazidime 99 patients, and vancomycin/ceftriaxone 51 patients. RESULT: Our results showed a low incidence of AKI in patients on vancomycin/PTZ concomitant treatment where overall incidence was only (4.8%) three cases and only one of them (2.0%) in a patient receiving the vancomycin/ceftriaxone concomitant treatment. No cases of AKI present in patients receiving vancomycin with ceftazidime or vancomycin alone. There were no statistically significant differences between the four treatment groups in terms of AKI incidence, vancomycin trough, and use of nephrotoxins. CONCLUSION: Overall, the incidence of AKI was low in our study sample with no statistically significant increased risk when PTZ was used in combination with vancomycin in a pediatric population. However, further investigation with an equal larger sample size is needed to confirm our findings.

Simple statistical channel model for weak temperature-induced turbulence in underwater wireless optical communication systems.

In this Letter, we use laser beam intensity fluctuation measurements to model and describe the statistical properties of weak temperature-induced turbulence in underwater wireless optical communication (UWOC) channels. UWOC channels with temperature gradients are modeled by the generalized gamma distribution (GGD) with an excellent goodness of fit to the measured data under all channel conditions. Meanwhile, thermally uniform channels are perfectly described by the simple gamma distribution which is a special case of GGD. To the best of our knowledge, this is the first model that comprehensively describes both thermally uniform and gradient-based UWOC channels.

Current umbilical cord clamping practices and attitudes of obstetricians and midwives toward delayed cord clamping in Saudi Arabia.

BACKGROUND: In Saudi Arabia, as in many countries, there is usually no clear definition of the timing of umbilical cord clamping (UCC) in the policies and procedures used by hospitals. The World Health Organization (WHO) recommends delayed cord clamping (DCC) ( > 1 minute after birth) as it can significantly improve hemodynamics and long-term neurodevelopment. OBJECTIVE: To investigate current practices of healthcare professionals on the timing of UCC in Saudi Arabia. DESIGN: Cross-sectional survey. SETTING: Five tertiary hospitals in Riyadh, Saudi Arabia, during May to October 2016. SUBJECTS AND METHODS: Obstetricians and midwives completed a widely-used questionnaire on UCC practices. MAIN OUTCOME MEASURE(S): Current UCC practices and attitudes of obstetricians and midwives toward DCC. RESULTS: Eighty-two obstetricians and 75 midwives completed the questionnaire for a response rate of 80%. The majority of respondents were aged 30 years or older (81%) and 84% were females. Most respondents were non-Saudi (66%) and had an educational level of bachelor's degree or higher (72%). Only 42% of respondents reported the existence of UCC guidelines in their practice; 38% reported the existence of a set time for UCC when the neonate was term and healthy, and only 32% had a set time for UCC in preterm neonates. While lower levels of agreement were reported among obstetricians and midwives on the benefits of DCC for babies requiring positive pressure ventilation, the majority of respondents (69-71%) thought that DCC was generally good for both term and preterm babies and that its benefits extend beyond the neonatal period. CONCLUSIONS: While the majority of obstetricians and midwives that participated in this study had a positive perception toward DCC, this did not translate to their daily practice as most of these professionals reported a lack of existing UCC guidelines in their institutions. Further studies are warranted to confirm these findings. LIMITATIONS: Participant selection by convenience sampling.

Extracellular vesicle mediated intercellular communication at the porcine maternal-fetal interface: A new paradigm for conceptus-endometrial cross-talk.

Exosomes and microvesicles are extracellular vesicles released from cells and can contain lipids, miRNAs and proteins that affect cells at distant sites. Recently, microvesicles containing miRNA have been implicated in uterine microenvironment of pigs, a species with unique epitheliochorial (non-invasive) placentation. Here we report a novel role of conceptus-derived exosomes/microvesicles (hereafter referred to as extracellular vesicles; EVs) in embryo-endometrial cross-talk. We also demonstrate the stimulatory effects of EVs (PTr2-Exo) derived from porcine trophectoderm-cells on various biological processes including the proliferation of maternal endothelial cells (PAOEC), potentially promoting angiogenesis. Transmission immuno-electron microscopy confirmed the presence of EVs in tissue biopsies, PTr2-Exo and PAOEC-derived EVs (PAOEC-Exo). RT-PCR detected 14 select miRNAs in CD63 positive EVs in which miR-126-5P, miR-296-5P, miR-16, and miR-17-5P were the most abundant angiogenic miRNAs. Proteomic analysis revealed EV proteins that play a role in angiogenesis. In-vitro experiments, using two representative cell lines of maternal-fetal interface, demonstrated bidirectional EVs shuttling between PTr2 and PAOEC cells. Importantly, these studies support the idea that PTr2-Exo and PAOEC-Exo containing select miRNAs and proteins can be successfully delivered to recipient cells and that they may have a biological role in conceptus-endometrial cross-talk crucial for the pregnancy success.

Nanomembrane-Based, Thermal-Transport Biosensor for Living Cells.

Knowledge of materials' thermal-transport properties, conductivity and diffusivity, is crucial for several applications within areas of biology, material science and engineering. Specifically, a microsized, flexible, biologically integrated thermal transport sensor is beneficial to a plethora of applications, ranging across plants physiological ecology and thermal imaging and treatment of cancerous cells, to thermal dissipation in flexible semiconductors and thermoelectrics. Living cells pose extra challenges, due to their small volumes and irregular curvilinear shapes. Here a novel approach of simultaneously measuring thermal conductivity and diffusivity of different materials and its applicability to single cells is demonstrated. This technique is based on increasing phonon-boundary-scattering rate in nanomembranes, having extremely low flexural rigidities, to induce a considerable spectral dependence of the bandgap-emission over excitation-laser intensity. It is demonstrated that once in contact with organic or inorganic materials, the nanomembranes' emission spectrally shift based on the material's thermal diffusivity and conductivity. This NM-based technique is further applied to differentiate between different types and subtypes of cancer cells, based on their thermal-transport properties. It is anticipated that this novel technique to enable an efficient single-cell thermal targeting, allow better modeling of cellular thermal distribution and enable novel diagnostic techniques based on variations of single-cell thermal-transport properties.

Altered expression of chemokines and their receptors at porcine maternal-fetal interface during early and mid-gestational fetal loss.

Chemokines play a significant role in pregnancy, especially during embryonic attachment and placental development. During early pregnancy, immune cells are recruited extensively to the endometrium in several species including pigs. However, this recruitment is solely mediated by the presence of the conceptus in pigs making it a unique feature compared with other species (humans, primates and mice). To understand the biological significance of chemokine expression and immune cell recruitment in the context of fetal loss, we investigate a well-characterized porcine fetal loss model during the window of early pregnancy at gestational day (gd) 20 and mid-pregnancy (gd50). These periods coincide with 25-40 % of conceptus loss. Using targeted quantitative polymerase chain reaction and Western blot approaches, we screened a specific set of chemokines. Comparisons were made with endometrial lymphocytes (ENDO LY), endometrium and chorioallantoic membranes (CAM) associated with spontaneously arresting and healthy conceptus attachment sites (CAS). mRNA expression studies revealed an increased expression of CXCR3 and CCR5 in ENDO LY and of CXCL10, CXCR3, CCL5 and CCR5 in the endometrium associated with arresting CAS at gd20. DARC was decreased in the endometrium at gd50. CCL1 was increased in CAM associated with arresting CAS at gd50. Some of these differences were also noted at the protein level (CXCL10, CXCR3, CCL5 and CCR5) in the endometrium and CAM. CD45+ immunohistochemistry demonstrated a significantly higher localization in ENDO LY in the endometrium associated with healthy versus arresting counterparts. Most of these differences were observed in early pregnancy and might contribute towards a shift in immune cell functions.

Droop-Free, Reliable, and High-Power InGaN/GaN Nanowire Light-Emitting Diodes for Monolithic Metal-Optoelectronics.

A droop-free nitride light-emitting diode (LED) with the capacity to operate beyond the "green gap" has been a subject of intense scientific and engineering interest. While several properties of nanowires on silicon make them promising for use in LED development, the high aspect ratio of individual nanowires and their laterally discontinuous features limit phonon transport and device performance. Here, we report on the monolithic integration of metal heat-sink and droop-free InGaN/GaN quantum-disks-in-nanowire LEDs emitting at ∼710 nm. The reliable operation of our uncooled nanowire-LEDs (NW-LEDs) epitaxially grown on molybdenum was evident in the constant-current soft burn-in performed on a 380 µm × 380 µm LED. The square LED sustained 600 mA electrical stress over an 8 h period, providing stable light output at maturity without catastrophic failure. The absence of carrier and phonon transport barriers in NW-LEDs was further inferred from current-dependent Raman measurements (up to 700 mA), which revealed the low self-heating. The radiative recombination rates of NW-LEDs between room temperature and 40 °C was not limited by Shockley-Read-Hall recombination, Auger recombination, or carrier leakage mechanisms, thus realizing droop-free operation. The discovery of reliable, droop-free devices constitutes significant progress toward the development of nanowires for practical applications. Our monolithic approach realized a high-performance device that will revolutionize the way high power, low-junction-temperature LED lamps are manufactured for solid-state lighting and for applications in high-temperature harsh environment.

Intrinsic determinants and predictors of superovulatory yields in sheep: Circulating concentrations of reproductive hormones, ovarian status, and antral follicular blood flow.

Hormonal ovarian superstimulation has contributed to small ruminant reproduction around the world, impacting genetic improvement and zoosanitary programs, contributing to the conservation of endangered species, and supporting other related biotechnologies. Advanced knowledge surrounding the superovulatory treatments in sheep has resulted in enhanced control of influencing factors and improved the protocols currently used. However, in spite of minimization of some adverse factors, superovulatory responses in ewes still remain variable, preventing the more widespread use of superovulation in commercial embryo transfer programs and reproductive research in this species. Recent evidence demonstrates that changes in antral follicular populations and blood supply, and circulating concentrations of certain reproductive hormones determined at the specific time points just before or during the superovulatory treatment are associated with superovulation success in ewes. This review attempts to compile the data from available literature to identify ovarian and hormonal determinants of the superovulatory outcome in ewes, which can be used to substantially improve the existing protocols and to reduce the extra cost and unnecessary stress imposed on poorly responding animals. An overview of most commonly used and some recently developed, FSH-based ovarian stimulation protocols is given at the outset to highlight variation in the frequency and timing of gonadotropin injections, estrus synchronization methods, and follicular wave synchronization and/or ovulation induction techniques during the superovulatory treatments in ewes.

Placentation, maternal-fetal interface, and conceptus loss in swine.

Pregnancy is a delicate yet complex physiological process that requires fine-tuning of many factors (hormones, growth factors, cytokines, and receptors) between the mother and the conceptus to ensure the survival of the conceptus(es) to term. Any disturbance in the maternal-conceptus dialog can have detrimental effects on the affected conceptus or even the outcome of pregnancy as a whole. Being a litter-bearing species, such disruptions can lead to a loss of up to 45% of the totally healthy offspring during early (periattachment) and midgestation to late gestation in pigs. Although the exact mechanism is not entirely understood, several factors have been associated with the fetal loss including but not limited to uterine capacity, placental efficiency, genetics, nutrition, and deficits in vascularization at the maternal-fetal interface. Over the years, we investigated how immune cells are recruited to the porcine maternal-fetal interface and whether they contribute to vascularization. We also delineated how cytokines, chemokines, and cytokine destabilizing factors fine-tune inflammation and whether the cytokine shift from early to midpregnancy exists at the porcine maternal-fetal interface. Finally, we evaluated the role of microRNAs in regulating immune cell recruitment and their angiogenic functions during pregnancy. Collectively our research points out that the immune-angiogenesis axis at the porcine maternal interface is significantly involved in promoting new blood vessel development, regulating inflammatory responses and ultimately contributing to pregnancy success. In this review, we summarized current knowledge on spontaneous fetal loss in swine, with special attention to the mechanisms in immune reactivity and interplay at the maternal-fetal interface.

Comparison of the effects of pretreatment with Veramix sponge (medroxyprogesterone acetate) or CIDR (natural progesterone) in combination with an injection of estradiol-17ß on ovarian activity, endocrine profiles, and embryo yields in cyclic ewes superovulated in the multiple-dose Folltropin-V (porcine FSH) regimen.

Follicular wave status at the beginning of exogenous FSH administration is an important contributor to variability in superovulatory responses in ruminants. Studies in ewes have shown a decrease in the number of ovulations when superovulation is initiated in the presence of ostensibly ovulatory-sized ovarian follicles. Hormonal ablation of large antral follicles with the progestin-estradiol (E2-17ß) treatment significantly reduces this variability in superovulated anestrous ewes, but the effects of the treatment in cycling ewes have not yet been assessed. Sixteen Rideau Arcott × Polled Dorset ewes (November-December) received either medroxyprogesterone acetate (MAP)-releasing intravaginal sponges (60 mg) or controlled internal drug release (CIDR) devices (containing 300 mg of natural progesterone) for 14 days (Days 0-14), with a single intramuscular injection of 350 µg of E2-17ß on Day 6. The superovulatory treatment consisted of six injections of porcine FSH (Folltropin-V) given twice daily, followed by a bolus GnRH injection (50 µg intramuscular) on Day 15. There were no differences (P < 0.05) in the ovulatory responses and embryo yields between the two groups of ewes. In both subsets of animals, the next follicular wave emerged ∼2.5 days after an E2-17ß injection (P > 0.05). A decline in maximum follicle size after an E2-17ß injection was more abrupt in CIDR- compared with MAP-treated animals, and the ewes pretreated with exogenous progesterone had significantly more 3-mm follicles at the start of the superovulatory treatment. The metabolic clearance rate of exogenous E2-17ß appeared to be greater in MAP-treated ewes, but circulating concentrations of porcine FSH failed to increase significantly after each Folltropin-V injection in CIDR-treated animals. The CIDR-treated ewes exceeded (P < 0.05) their MAP-treated counterparts in serum E2-17ß concentrations during superovulation. In spite of differences in antral follicle numbers and endocrine profiles between MAP- and CIDR-treated cyclic ewes receiving E2-17ß before ovarian superstimulation, there were no differences in superovulatory responses.

Distinct microRNA expression in endometrial lymphocytes, endometrium, and trophoblast during spontaneous porcine fetal loss.

Endometrial lymphocytes are recruited to the porcine maternal-fetal interface by conceptus-derived signals. The transiently recruited lymphocytes adopt a specialized phenotype in the endometrium that regulates various placental physiological processes, including angiogenesis. Small non-coding RNAs, microRNAs (miRNAs) are emerging as principal bio-molecules regulating the development of lymphocytes and their angiogenic functions. However, no information is available in the context of endometrial lymphocytes in pregnancy. We hypothesize that miRNAs are involved in the development of endometrial lymphocytes and their angiogenic functions at the porcine maternal-fetal interface. Using a targeted Q-PCR approach for selected miRNAs involved in immune cell development, angiogenesis, and anti-angiogenesis, we conducted a study to screen endometrial lymphocytes associated with healthy and spontaneously arresting conceptus attachment sites (CAS) at two well-defined periods of fetal loss. Comparisons were made with endometrium and trophoblasts associated with healthy and arresting CAS. In addition, levels of putative mRNA targets and subsequent functional clustering of genes were studied in order to predict the biological mechanisms affected. We found several significant differences for miRNAs involved in immune cell development and angiogenesis (miR-296-5P, miR-150, miR-17P-5P, miR-18a, and miR-19a) between endometrial lymphocytes associated with healthy and arresting CAS. Significant differences were also found in endometrium and trophoblasts for some miRNAs (miR-20b, miR-17-5P, miR-18a, miR-15b-5P, and miR-222). Finally, selected mRNA targets showed differential expression in all groups. Our data, although associative, are the first to unravel the selected miRNAs involved in immune cell development and provide insights into their possible regulation in abortive pregnancy.

mRNA destabilizing factors: tristetraprolin expression at the porcine maternal-fetal interface.

PROBLEM: To evaluate the expression of the tristetraprolin family and their selected targets during porcine pregnancy. METHOD OF STUDY: Using qPCR and Western blot, mRNA and protein levels were compared between endometrium and chorioallantoic membrane (CAM) associated with healthy and impaired conceptuses at gestation day (gd) 20 and gd50, respectively. Immunohistochemistry was performed to determine localization of TIS11 family members at gd20 and 50. RESULTS: Multiple significant differences (P < 0.05) in TIS11 family transcripts were observed in the aforementioned comparisons. GM-CSF was significantly higher in healthy endometrium and CAM from impaired conceptus attachment sites. TNF-α was elevated in CAM as compared to endometrium at gd50, regardless of conceptus health status. Immunohistochemical staining shows TIS11 family expressed in the glandular and luminal epithelium, as well as stromal cells in the uterus. CONCLUSIONS: The shift in the expression of tristetraprolin (TTP) and TIS11D points to a potential role of these genes in regulating spontaneous fetal loss.