Impact of SARS-CoV-2 Pandemic on Antiretroviral Access at a Large Treatment Centre in Lagos, Nigeria.

INTRODUCTION: The SARS-CoV-2 pandemic has ravaged the world with significant implications on the socio-economic and health status of individuals. Several measures were put in place to curtail the pandemic especially movement restrictions. The effect of this pandemic and the restriction measures could further compound the health needs of PLWHA. This study thus described the trend in access to HIV/AIDS care services before and during the COVID-19 induced lockdown and the possible consequences on their treatment outcome. METHODS: A secondary analysis of client data was carried out at the HIV clinic of the Nigerian Institute of Medical Research. The sociodemographic and clinical data [type of ART, duration on ART, clinical services 3-months before and during the COVID-19 induced Lockdown] were extracted from the electronic medical records. Data obtained was analyzed using the SPSS version 22.0. RESULTS: The median age of PLWHA was 45 years (IQR: 39-51), with the predominant age group being 25-49 years (65.4%). The majority were females (68.7%), married (59.5%), had at least secondary education (82.8%), and employed (81.5%). The median duration on ART was 102 months (IQR: 67-138) with the majority on non-Protease Inhibitor based regimen (77.7%). In the 3 months before the lockdown, there was an increase in drug pick-up of approximately 25% over the booked appointment compared to a decline of 40% when the lockdown was enacted. CONCLUSION: The significant decline in drug pick-up during the SARS-CoV-2 pandemic raises the need for measures to ensure continued access to drugs and care among PLWHA.

INTRODUCTION: La pandémie de SRAS-CoV-2 a ravagé le monde avec des implications significatives sur l'état socio- économique et sanitaire. Plusieurs mesures ont été mises en place pour freiner la pandémie, en particulier la restriction des déplacements. L'effet de cette pandémie et les mesures de restriction pourraient encore aggraver les besoins de santé des PVVIH. Cette étude décrit ainsi la tendance des services de soins du VIH / SIDA avant et pendant le verrouillage induit par le COVID-19 et les conséquences possibles sur l'issue de leur traitement. MÉTHODES: Une étude transversale parmi les PVVIH fréquentant la clinique VIH de l'Institut nigérian de recherche médicale. Les données sociodémographiques et cliniques [type de TAR, durée de la TAR, services cliniques 3 mois avant et pendant le verrouillage induit par COVID-19] ont été extraites des dossiers médicaux électroniques. Les données obtenues ont été analysées à l'aide de la version 22.0 de SPSS. RÉSULTATS: L'âge médian des PVVIH était de 45 ans (IQR (39-51), le groupe d'âge prédominant étant 25-49 ans (65,4%). La majorité étaient des femmes (68,7%), mariées (59,5%), avaient au moins secondaire (82,8%) et employé (81,5%). La durée médiane des TAR était de 102 mois (IQR: 67-138), la majorité sous traitement sans inhibiteur de protéase (77,7%). Au cours des 3 mois précédant le verrouillage , il y a eu une augmentation de la cueillette de médicaments d'environ 25% par rapport au rendez-vous réservé, comparativement à une baisse de 40% lorsque le verrouillage a été décrété. CONCLUSION: La baisse significative de la collecte de médicaments pendant la pandémie de SRAS-CoV-2 fait ressortir la nécessité de prendre des mesures pour assurer un accès continu aux médicaments et aux soins parmi les PVVIH. Mots Clés: SRAS-CoV-2, antirétroviral, COVID-19, ramassage de médicaments, VIH, verrouillage.

Unravelling the role of 17ß-estradiol on advancing uterine luteolytic cascade in cattle.

In cattle, 17ß-estradiol (E2) stimulates prostaglandin F2α (PGF2α) synthesis, which causes luteolysis. Except for the well-established upregulation of oxytocin receptor gene (OXTR), molecular mechanisms of E2-induced PGF2α release in vivo remain unknown. We hypothesized that E2-induced PGF2α release requires de novo transcription of components of the PGF2α synthesis machinery. Beef cows (n = 52) were assigned to remain untreated (Control; n = 10), to receive 50% ethanol infusion intravenously (Placebo; n = 21), or 3 mg E2 in 50% ethanol infusion intravenously (Estradiol; n = 21) on day 15 (D15) after estrus. We collected a single endometrial biopsy per animal at the time of the treatment (0h; Control B0h group), 4 hours (4h; Placebo B4h group and Estradiol B4h group), or 7 hours (7h; Placebo B7h group and Estradiol B7h group) post-treatment. Compared to the Placebo group, the Estradiol group presented significantly greater 13,14-dihydro-15-keto-PGF2α concentrations between 4h and 7h and underwent earlier luteolysis. At 4h, the qPCR analysis showed a lower abundance of ESR1, ESR2 and aldo-keto reductase family 1 member B1 (AKR1B1) genes in the Estradiol B4h group, and a greater abundance of OXTR compared to the Placebo B4h group. Similarly, the E2 treatment significantly reduced the abundance of AKR1B1, and AKR1C4 in the Estradiol B7h group, compared to the placebo group. Overall, E2-induced PGF2α release and luteolysis involved an unexpected and transient downregulation of components of the PGF2α-synthesis cascade, except for OXTR, which was upregulated. Collectively, our data suggest that E2 connects newly-synthesized OXTR to pre-existing cellular machinery to synthesize PGF2α and cause luteal regression.

Puberty attainment and reproductive performance of yearling Bos indicus-influenced heifers after two sequential treatments with progesterone.

Number of pubertal heifers at time of breeding season initiation is a primary determinant to pregnancy success during the breeding season. It was hypothesized that pre-breeding progesterone (P4) supplementation (induction) would increase the number of heifers pubertal at the time of imposing estrous synchronization treatment regimens and P/AI. Yearling, Bos indicus-influenced (n = 577) or Bos indicus (n = 174) heifers were or were not treated with P4 (CIDR and Non-CIDR, respectively) for 10 d starting on D-23 (D0 = TAI). Presence of a CL on D-33 or D-23 was considered to indicate heifers were pubertal. On D-13, there was a PGF analogue administered. On D-9, there was treatment with GnRH analogue, 6d-CIDR and PGF. There were inseminations based on estrus (D-2 to D0) or TAI on D0 for non-estrous animals. There were 5.2 % and 62.9 % purebred and crossbred heifers pubertal, respectively. Proportion of prepubertal crossbred than purebred heifers with CL on D-3 was greater as a result of imposing the pubertal induction regimen (P < 0.05 and P> 0.10, respectively). Regardless of puberty status, proportion of heifers in estrus prior to AI in the CIDR group was similar to the heifers of the Non-CIDR group for crossbreds and purebreds. Similarly, P/AI of CIDR group was similar to the Non-CIDR group for crossbreds and purebreds. In summary, imposing the pubertal induction regimen hastened attainment of puberty in yearling crossbred, but not purebred heifers. Puberty induction did not affect estrous response, neither fertility after imposing an estrous synchronization treatment regimen.

Migration and season explain tick prevalence in Brazilian birds.

Neotropical birds are mostly parasitized by immature ticks and act as reservoir hosts of tick-borne pathogens of medical and veterinary interest. Hence, determining the factors that enable ticks to encounter these highly mobile hosts and increase the potential for tick dispersal throughout migratory flyways are important for understanding tick-borne disease transmission. We used 9682 individual birds from 572 species surveyed across Brazil and Bayesian models to disentangle possible avian host traits and climatic drivers of infestation probabilities, accounting for avian host phylogenetic relationships and spatiotemporal factors that may influence tick prevalence. Our models revealed that the probability of an individual bird being infested with tick larvae and nymphs was lower in partial migrant hosts and during the wet season. Notably, infestation probability increased in areas with a higher proportion of partial migrant birds. Other avian ecological traits known to influence tick prevalence (foraging habitat and body mass) and environmental condition that might constrain tick abundance (annual precipitation and minimum temperature) did not explain infestation probability. Our findings suggest that migratory flyways harbouring a greater abundance of migrant bird hosts also harbour a higher prevalence of immature ticks with potential to enhance the local transmission of tick-borne pathogens and spread across regions.

Parasitism of a capybara (Hydrochoerus hydrochaeris) by Amblyomma nodosum Neumann, 1899 and Amblyomma humerale Koch, 1844 in an Amazon forest area, Rondônia, Brazil / [Parasitismo por Amblyomma nodosum Neumann, 1899 e Amblyomma humerale Koch, 1844 em capivara (Hydrochoerus hydrochaeris) em área de Floresta Amazônica, Rondônia, Brasil]

Dois carrapatos adultos, sendo um Amblyomma nodosum e um Amblyomma humerale foram encontrados parasitando ativamente uma capivara (Hydrochoerus hydrochaeris) proveniente da região central do estado de Rondônia, Brasil, na zona rural do município de Ji-Paraná, localizado na Amazônia ocidental. Poucos trabalhos científicos relatam a presença de A. humerale em capivaras. Assim, esta é a primeira vez que A. nodosum é relatado parasitando essa espécie animal. Por não se tratar de um hospedeiro animal conhecido para A. nodosum ou comum para A. humerale, esses achados podem sugerir uma nova relação entre hospedeiros para eles. Portanto, são necessários mais estudos acerca da ecologia desses parasitas, principalmente por serem potenciais transmissores de patógenos de importância em medicina veterinária e saúde pública.(AU)

Spinal subarachnoid haematoma after neuraxial anaesthesia in a patient with polycythaemia vera.

Polycythaemia vera is a common haematological proliferative disorder. It is characterised by uncontrolled red cell production with ensuing peri-operative vaso-occlusive and haemorrhagic complications. Spinal haematoma after neuraxial anaesthesia is rare; most cases are associated with technical difficulties or bleeding disorders. Current consensus opinion suggests that neuraxial anaesthesia in patients with polycythaemia vera is safe due to a lower risk of thrombotic events and hypoxaemia compared with general anaesthesia. We report a case of a spinal subarachnoid haematoma after uneventful neuraxial anaesthesia in a patient with optimised polycythaemia vera. Despite an emergent laminectomy, the patient developed permanent motor deficits. This report highlights that although neuraxial anaesthesia is recommended by many authors, patients with polycythaemia vera can paradoxically have an increased haemorrhagic risk from platelet dysfunction and acquired von Willebrand disease. Clinicians proceeding with surgery under neuraxial anaesthesia should appreciate these risks even in patients with normal or apparently elevated thrombotic states. This case also demonstrates that traditional coagulation tests may need to be complemented by pre-operative platelet function tests and screening for von Willebrand disease. Finally, the importance of the patient participation in the choice of the anaesthesia technique cannot be understated, with specific attention paid to this frequently unrecognised risk.

Pitavastatin ameliorates autoimmune neuroinflammation by regulating the Treg/Th17 cell balance through inhibition of mevalonate metabolism.

While Treg cells are responsible for self-tolerance and immune homeostasis, pathogenic autoreactive Th17 cells produce pro-inflammatory cytokines that lead to tissue damage associated with autoimmunity, as observed in multiple sclerosis. Therefore, the immunological balance between Th17 and Treg cells may represent a promising option for immune therapy. Statin drugs are used to treat dyslipidemia; however, besides their effects on preventing cardiovascular diseases, statins also have anti-inflammatory effects. Here, we investigated the role of pitavastatin on experimental autoimmune encephalomyelitis (EAE) and the differentiation of Treg and Th17 cells. EAE was induced by immunizing C57BL/6 mice with MOG35-55. EAE severity was determined by analyzing the clinical score and inflammatory parameters in the spinal cord. Naive CD4 T cells were cultured under Treg and Th17-skewing conditions in vitro in the presence of pitavastatin. We found that pitavastatin decreased EAE development, which was accompanied by a reduction of all parameters investigated. Pitavastatin also reduced the expression of IBA1 and pSTAT3 (Y705 and S727) in the spinal cords of EAE mice. Interestingly, the reduction of Th17 cell frequency in the draining lymph nodes of EAE mice treated with pitavastatin was followed by an increase of Treg cells. Indeed, pitavastatin directly affects T cell differentiation in vitro by decreasing Th17 and increasing Treg cell differentiation. Mechanistically, pitavastatin effects are dependent on mevalonate synthesis. Thus, our data show the potential anti-inflammatory effect of pitavastatin on the pathogenesis of the experimental neuroinflammation by modulating the Th17/Treg axis.

Effects of cryolipolysis with adiposity plates located with the Crioplace concept in women.

BACKGROUND: Cryolipolysis with plates is a method of applying cooling without a vacuum system, which can be used in regions with less chance of forming a "crease." OBJECTIVE: To investigate the effects of cryolipolysis using a plate-shaped applicator (Crioplac) in the treatment of fat. MATERIALS AND METHODS: This is an experimental study in which women aged 25 to 45 years with adiposity located in the abdomen participated. Two applications of 75 min were made, using 04 plates in the abdomen regions, with -4 degree C being programmed as a temperature parameter. Anthropometric and ultrasound assessments were performed, and a satisfaction questionnaire on the validated treatment was conducted. The reassessments were performed 30 and 60 days after the first intervention. RESULTS: A reduction in adiposity was observed in the measurements of perimetry, plicometry and abdominal ultrasound (p<0.05). It was found that about 62.5% of the volunteers reported an improvement in water retention, about 62.5% reported the presence of loose clothing, and 31.3% reported satisfaction with the results obtained. It was observed that 18.5% of the volunteers reported that the treatment was excellent. CONCLUSION: The Crioplace method proved to be effective in reducing adiposity, with a high clinical satisfaction with the reduction in body measurements.

Effect of a puberty induction protocol based on injectable long acting progesterone on pregnancy success of beef heifers serviced by TAI.

Induction protocols based on progesterone (P4) are used prior to a synchronization program for timed-AI (TAI) to increase number of pubertal heifers and pregnancy per AI (P/AI). Injectable, long-lasting P4 (iP4) is a novel, practical method to supplement P4 in cattle. Here, we aimed to test the effect of an induction protocol based on a single injection of iP4 on P/AI of heifers. Bos indicus (Nellore) heifers were classified as pubertal (PUB; n = 224) or prepubertal (PRE; n = 414) based on two ovarian ultrasonographyc exams conducted 10 d apart. Heifers with a corpus luteum (CL) in any of the exams were considered PUB. Within each puberty status, heifers were assigned to receive nothing (NoiP4) or an induction protocol (iP4). Induction consisted of a single injection of 150 mg of iP4 on D-31, followed by injections of 1 mg of estradiol benzoate (EB) and 150 µg of prostaglandin analogue (PGF) on D-21. On D-9, all heifers received 2 mg of EB + 75 µg of PGF associated to intravaginal P4-device insertion. On D-3, P4-releasing devices were removed and 150 µg of PGF injected. Heifers were inseminated based on estrus on D-1 or were TAI on D0. On D0, all heifers received a dose of GnRH analogue. On D-21, iP4 treatment stimulated a 50% increase in the uterine score (UTS) and a 19% increase in the diameter of the largest follicle of PRE heifers (P < 0.01). On D-9, PRE|iP4 group had a greater proportion (P < 0.01) of CL (63.3%) than PRE|NoiP4 group (11.6%). On D-3, exposure to 6 d P4-releasing device stimulated UTS of PRE|NoiP4 group in a similar fashion than the induction protocol, but it did not have any additional positive effect for PRE|iP4 heifers. P/AI of PRE|iP4 group was similar to that of the PUB groups (44.7 vs 46.9%), but was more than that of PRE|NoiP4 (34.2%). There was an overall 7.7% increment (P = 0.07) on P/AI of iP4 treated heifers (iP4: 46.0% vs. NoiP4: 38.3%). In conclusion, implementation of an induction protocol based on iP4 was efficacious to hasten puberty. Induction stimulated uterine development and follicular growth of prepubertal heifers, ultimately leading to pregnancy success similar to that of pubertal heifers.

Artificial neural networks for prediction of recurrent venous thromboembolism.

BACKGROUND: Recurrent venous thromboembolism (RVTE) is a multifactorial disease with occurrence rates which vary from 13 % to 25 % in 5 years after the initial event. Once a patient the first thrombotic event, the probability of recurrence should be determined, as well as the most adequate anticoagulant therapy. To our knowledge based on the published literature, three statistical models have been proposed to calculate RVTE probability. However, these models present several limitations, such as: limited input variables, lack of external validation and applicability only for patients with a first unprovoked thrombosis. Additionally, some of the models have been recognized to fail in determining RVTE when patients have a low risk of recurrence. OBJECTIVE: An alternative procedure in which three Artificial Neural Network (ANN) models were developed to classify which patients will present RVTE based solely on clinical data. METHODS: Data of 39 clinical factors from 235 patients were used to train several ANN structures. The difference among the three models was its inputs. In ANN 1, the inputs were all 39 factors. In ANN 2, 18 factors determined previously as the main predictors of RTVE using Principal Component Analysis (PCA). Finally, in ANN 3, 15 factors combining PCA results with practical aspects. Different number of hidden layers and neurons, and three optimization algorithms were considered. 5-fold cross validation was also performed. RESULTS: The results showed that all models were capable of performing this task. Different optimization algorithms lead to different results. The best models presented high accuracy. The best structures were 39-10-10-1, 18-10-5-1, and 15-15-10-1 for ANN 1, ANN 2, and ANN 3 models, respectively. The cross-validation showed that the results are consistent. CONCLUSIONS: This work showed that the association of multivariate techniques and ANNs is a powerful tool that can be used to model a complex phenomenon such as RVTE without the restrictions of existing approaches. APPLICATION: After proper validation, these ANN models can be used to help clinicians with decisions regarding VTE treatment.

Marsupialization for the treatment of nictitating membrane cyst in a dog: case report / Marsupialização para o tratamento de cisto em membrana nictitante de cão: relato de caso

This study aims to describe the first Brazilian report of a nictitating membrane cyst's surgical treatment in a dog. A 6-month-old female French Bulldog presented at HOSVET-UNIME with a reddish mass-like structure in the medial canthus of both eyes, with a history of recurrent third eyelid gland prolapse previously treated with two surgeries performed at another clinic. Physical examination revealed a third eyelid gland prolapse in the right eye and a cyst in the left eye's third eyelid. The animal was submitted to surgical correction of the right eye's third eyelid prolapse using pocket technique and of the left eye's third eyelid using marsupialization technique for the cyst's treatment. 180 days after th1e surgical procedure no recurrence was observed. The marsupialization technique for the treatment of a third eyelid's lacrimal cyst in a dog allowed the maintenance of its gland and prevented the formation of a new cystic cavity.(AU)

O objetivo do presente trabalho é descrever o primeiro relato no Brasil de tratamento cirúrgico de um cisto da membrana nictitante em um cão. Um Buldogue Francês, fêmea, seis meses, foi atendido no Hosvet-Unime, com queixa de aumento de volume avermelhado no canto medial de ambos os olhos, com histórico de recidiva de prolapso de glândula da terceira pálpebra, onde haviam sido realizadas duas cirurgias anteriormente em outro local. Ao exame físico, foi observado prolapso de glândula da terceira pálpebra no olho direito e a presença de um cisto na terceira pálpebra do olho esquerdo. O animal foi submetido ao procedimento cirúrgico de sepultamento de glândula da terceira pálpebra no olho direito e uma marsupialização na terceira pálpebra do olho esquerdo para o tratamento do cisto. Cento e oitenta dias após o procedimento cirúrgico, não foi observada recidiva. A técnica de marsupialização para tratamento de cisto lacrimal na terceira pálpebra em um cão possibilitou a manutenção da sua glândula e impediu a formação de nova cavidade cística.(AU)

Experimental manipulation of beliefs about the importance of thoughts and the effect on an aggressive impulse.

BACKGROUND: Cognitive models of obsessive-compulsive disorder attribute a causal role to maladaptive beliefs. AIMS: To test this hypothesis, we manipulated Overimportance of Thoughts (OT) beliefs and experimentally evaluated their effect on the response to an induced aggressive impulse. METHOD: Eighty-five participants completed a battery of self-report instruments assessing obsession symptoms, thought control, affectivity and obsessive beliefs, and were then randomly assigned to two conditions. In the experimental condition participants read a scientific abstract on the importance of thought control whilst those in the control condition read a neutral abstract. All participants identified a loved person and imagined feeling the impulse to stab this person, then completed again OT beliefs measures (Overimportance of Thought, Moral-Thought Action Fusion and Thought Action Fusion Likelihood). RESULTS: The Moral component of the Thought Action Fusion was reduced by reading a brief text about the possibility and desirability of thought control. However, experimentally induced changes in beliefs did not yield differences in the intrusiveness of the aggressive impulse. CONCLUSIONS: Some beliefs can be modified through a single session in which information similar to what could be obtained in quotidian life is provided.

Molecular identification of Ehrlichia sp. in a beef cattle from Brazilian Cerrado - case report / Identificação molecular de Ehrlichia sp em um bovino do Cerrado brasileiro - relato de caso

Ehrlichia infections in cattle are frequent in Africa but have also been reported in Brazil and North America. This paper reports natural infection by Ehrlichia sp. associated with Babesia bigemina and Anaplasma marginale in a calf in the municipality of Campo Grande, state of Mato Grosso do Sul, Brazil, presenting polioencephalomalacia. The molecular evidence, based on a fragment of the dsb gene, indicates a species of Ehrlichia genetically related to Ehrlichia canis and other species of the genus found in the tick Rhipicephalus (Boophilus) microplus and a calf from Brazil (99 to 100% identity). It was not possible to associate the clinical signs with Ehrlichia infection due to co-infections and histological evidence of another disease. However, the circulation of the bacteria in bovines in Brazilian Cerrado was confirmed and more attention should be given to clinical suspicion of tick-borne pathogens in cattle to clarify the pathogenic potential of Ehrlichia sp.(AU)

Infecções por Ehrlichia em bovinos são frequentes na África, mas também foram relatadas no Brasil e na América do Norte. Este artigo relata uma infecção natural por Ehrlichia sp. associado a Babesia bigemina e Anaplasma marginale em um bezerro, no município de Campo Grande, Mato Grosso do Sul, Brasil, o qual apresentava polioencefalomalácia. A evidência molecular, baseada em um fragmento do gene dsb, indica uma espécie de Ehrlichia geneticamente relacionada a Ehrlichia canis e outras espécies do gênero encontradas no carrapato Rhipicephalus (Boophilus) microplus e em um bezerro do Brasil (99 a 100% de identidade). Não foi possível associar os sinais clínicos à infecção por Ehrlichia devido a coinfecções e evidências histológicas de outra doença. No entanto, a circulação da bactéria em bovinos no Cerrado brasileiro foi confirmada, e mais atenção deve ser dada à suspeita clínica de patógenos transmitidos por carrapatos em bovinos para esclarecer o potencial patogênico de Ehrlichia sp.(AU)

Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents.

Surpassing heart diseases, cancer is taking the lead as the deadliest disease because of its fast rate of spreading in all parts of the world. Tireless commitment to searching for novel therapeutic medicines is a worthwhile adventure in synthetic chemistry because of the drug resistance predicament and regular outbreak of new diseases due to abnormal cell growth and proliferation. Medicinal chemistry researchers and pharmacists have unveiled quinoxaline templates as precursors of importance and valuable intermediates in drug discovery because they have been established to possess diverse pharmacological potentials. Hence, this review highlights the current versatile routes to accessing functionalized quinoxaline motifs and harnessing their documented therapeutic potentials for anticancer drug development.

Small for gestational age very preterm infants present a higher risk of developing bronchopulmonary dysplasia.

INTRODUCTION: Several studies assessed the influence of a low birth weight on bronchopulmonary dysplasia (BPD), but not all could find a significant association. Our aim was to assess the association between low birth weight and BPD in preterm infants, prospectively recruited at 11 level III Portuguese neonatal centers. METHODS: Obstetrical and neonatal data on mothers and preterm infants with gestational ages between 24 and 30 weeks, born during 2015 and 2016 after a surveilled pregnancy, were analyzed. Neonates were considered small for gestational age (SGA) when their birthweight was below the 10th centile of Fenton's growth chats and BPD was defined as the dependency for oxygen therapy until 36 weeks of corrected age. Statistical analysis was performed using IBM SPSS® statistics 23 and a p-value <0.05 was considered statistically significant. RESULTS: Out of 614, a total of 494 preterm infants delivered from 410 women were enrolled in the study; 40 (8.0%) infants with SGA criteria. SGA were more often associated with a single pregnancy, had greater use of antenatal corticosteroids, increased prevalence of gestational hypertensive disorders, C-section, rupture of membranes below 18 hours, rate of intubation in the delivery room, use of surfactant treatment, oxygen therapy, mechanical ventilation need, BPD, cystic periventricular leukomalacia, nosocomial sepsis and pneumonia; had lower prevalence of chorioamnionitis, and lower Apgar scores. The multivariate analysis by logistic regression, adjusted for BPD risk factors revealed a significant association between SGA and BPD: OR = 5.2 [CI: 1.46-18.58]; p = 0.01. CONCLUSION: The results of this study increase the scientific evidence that SGA is an independent risk factor for BPD.

Supplementation with long-acting progesterone in early diestrus in beef cattle: I. effect of artificial insemination on onset of luteolysis.

Progesterone (P4) supplementation in early diestrus advances changes in the endometrial transcriptome, stimulating embryonic development. However, it also induces early onset of luteolysis. Occurrence of luteolysis before D16 postmating can be detrimental to fertility. A potential counteracting role of the elongating conceptus on early luteolysis is understood poorly. The aim of the study was to evaluate the effect of artificial insemination (AI; ie, pregnancy) on the temporal dynamics of luteolysis of cows supplemented with P4. Nonsuckled beef cows were inseminated at 12 h after estrus (D0: ovulation) or were not inseminated (no-AI). On D3, the AI cows were assigned to receive a single dose of 150 mg of injectable long-acting P4 via intramuscular injection (AI + iP4; n = 23), and the no-AI cows were assigned to receive iP4 (iP4; n = 21) or saline (control, n = 22). Corpus luteum (CL) development and regression were determined by ultrasonography (US) between D3 and D21. Plasma P4 concentrations were measured on D3 and every other day from D9 to D21. Pregnancy status was determined by US (D28‒D32). iP4 supplementation reduced luteal development (D5-D10) compared to the control group and increased incidence of luteolysis between D14 and D15. On D15, the proportion of cows that underwent luteolysis and plasma P4 concentrations differed between the iP4 group (47.6; 2.10 ± 0.47) and the control group (13.6; 4.40 ± 0.46) and was intermediate in the AI + iP4 group, respectively (26.1%; 3.70 ± 0.45 ng/mL; P < 0.05). The AI effects were due to the pregnant cows (n = 7). Considering nonpregnant cows only, the proportion of early luteolysis in the AI + iP4 group (37.5%) was similar to the iP4 group. Pregnancy was not established in cows having a shortened luteal lifespan. Indeed, interval to luteolysis in the AI + iP4 group (15.50 ± 0.66 d) was similar to the iP4 group (16.38 ± 0.46 d), but less than the control group (17.38 ± 0.40 d; P = 0.05). In conclusion, the effect of AI on extending luteal lifespan occurred exclusively in cows that maintained pregnancy.

Supplementation with long-acting progesterone in early diestrus in beef cattle: II. Relationships between follicle growth dynamics and luteolysis.

The aims were to characterize follicular dynamics in response to supplemental progesterone (P4) and to investigate the relationships between follicular growth and onset of luteolysis in P4-treated cows, submitted or not to artificial insemination (AI). Nonsuckled beef cows detected in estrus were assigned to receive AI or to remain non-AI. Three days after ovulation (ie, D3), AI cows were injected with 150 mg of long-acting P4 (AI + injectable P4 formulation [iP4]; n = 22), and the non-AI cows were assigned to receive 150 mg iP4 (n = 19) or saline (control, n = 19). Between D3 and D21, growth dynamics of the dominant follicles (DFs) was monitored by ultrasonography. Plasma P4 concentrations were measured every other day from D9 to D19. Pregnancy status (ie, P: pregnant and NP: nonpregnant) was examined by ultrasound on D28 to D32. Injectable P4 formulation supplementation decreased average maximum diameter of first-wave DF (DF1). Neither day of emergence of DF2 or DF3 nor the proportion of two- or three-wave cycles were altered by supplemental P4. Daily mean diameter of DF2 and DF3 was also similar between control and iP4 groups. Consistently, daily mean diameter of DF1 in iP4-treated cows was smaller for cows that underwent luteolysis by D15 compared to a later onset. Progesterone concentrations between D9 and D19 decreased earliest in the iP4 group, latest in the control group and was intermediate for the NP-AI + iP4 group. In addition, three-wave cycles presented a delayed decrease on plasma P4 concentrations than two-wave cycles. Further analysis revealed that on two-wave cycles, P4 concentrations on D15 were lowest in the iP4 and NP-AI + iP4 animals compared to the control and P-AI + iP4 groups. Conversely, for three-wave cycles, on D15, P-AI + iP4, NP-AI + iP4, and controls had greater P4 concentrations than the iP4 group. In summary, our data indicate that impairment of first follicular growth was associated with P4-induced shortened luteal lifespan (D14-D15) and that three-wave cycles after AI can be more supportive for pregnancy maintenance in P4-treated cows. We speculate that such conditions play a critical role in the embryonic ability to inhibit iP4-induced early luteolysis reported in part I of this series.

Exacerbated conceptus signaling does not favor establishment of pregnancy in beef cattle.

BACKGROUND: Insufficient production of anti-luteolytic signals by the pre-attachment embryo is considered a major cause of pregnancy failure in cattle. We tested the hypothesis that transfer of multiple blastocysts (n = 5/recipient) and progesterone (P4) supplementation amplify anti-luteolytic signaling and reduce embryonic losses in beef cattle. Cows detected in estrus (D0; n = 104) were assigned randomly to receive 150 mg of injectable long-acting P4 (iP4) or vehicle (non-iP4) on D4 and transcervical transfer of none or five, grade 1, not-frozen, in vitro-produced blastocysts, on D7. Luteal development and time of structural luteolysis were monitored by ultrasonography. Plasma P4 concentrations were determined on D4, D5 and D7, and daily between D14 and D20. Conceptus signaling was monitored by transcript abundance of interferon-stimulated gene 15 (ISG15) in peripheral blood mononuclear cells isolated on D14, D16, D18 and D20. Early embryonic mortality (EEM) was defined as the absence of ISG15 mRNA upregulation over time and/or luteal regression up to D20. Late embryonic mortality (LEM) was defined as the absence of a conceptus with a heartbeat on pregnancy diagnosis at D30 (PD30) after observing upregulation of ISG15 mRNA and extension of luteal lifespan. Pregnant cows presented conceptuses with heartbeat at PD30. RESULTS: On D5, iP4-treated cows had P4 concentrations 2.07-fold greater than non-iP4 treated (P < 0.001). On D7, P4 concentrations were similar. Pregnant and LEM animals showed a progressive increase in the abundance of ISG15 from D14 to D20. iP4-treated cows detected pregnant at PD30 had 1.53-fold greater abundance of ISG15 mRNA between D14 and D20 than non-iP4 treated cows (P = 0.05). iP4 doubled the frequency of EEM while it did not affect LEM. At PD30, embryonic survival was 37.0% vs. 55.6% for iP4-treated vs. control cows. Majority of pregnant cows (71%) presented only a single viable embryo. CONCLUSIONS: A substantial proportion of cows had EEM (31%) and LEM (20%) even after transferring multiple blastocysts. This argues that mortality was due to poor uterine receptivity that could not be reversed by supplemental P4 or overcome by transferring multiple blastocysts. Further, a given uterine environment was not necessarily adequate to all embryos.

Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice.

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16-/- without treatment, group II: treated HPV16-/-, group III: HPV16+/- without treatment and group IV: treated HPV16+/-). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wild-type animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.