Genetic variants of APEX1 p.Asp148Glu and XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma.

The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma (HCC). The foremost objective of this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of HCC and to identify the computational bioinformatics frameworks of these missense variants. A total of 250 participants were enrolled in this study, including 150 HCC patients and 100 cancer-free controls. The genomic DNA was characterized and genotyped by applying the PCR-CTPP method. The frequency of the APEX1 (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12-2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42-0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (p > .05). Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC.

Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex and the possible protective role of folic acid.

BACKGROUND: Valproic acid (VPA), one of the most important antiepileptic drugs, proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the foetuses and mothers. Periconceptional folic acid supple-mentation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity. MATERIALS AND METHODS: Twenty-four pregnant female albino rats were divided into three groups; group I (control group, did not receive any drugs), group II (given VPA at a dose of 50 mg/kg body weight once daily) and group III (given the same dose of VPA and 400 µg/kg of body weight folic acid once daily). Ten male offspring from each group were sacrificed at two ages: at 2 and 12 weeks after birth. Samples of cerebellar cortex were taken and prepared for light, electron microscopic examination, glial fibrillary acidic protein (GFAP) immunohistochemical study and histomorphometric analysis. RESULTS: The present study confirmed the neurotoxic effect of prenatal VPA on the cerebellar cortex, especially on Purkinje cells. The cells appeared shrunken, reduced in density, disorganised and surrounded by empty haloes. Nuclear damage and axon degeneration in the form of vacuolation, loss of organelles and absence of neurofilaments with myelin sheath depletion were detected. Concomitant supply of folic acid was shown to retain the normal architecture of Purkinje cells with their axons and nuclei. In many animals receiving folic acid, the thickness of all layers of the cortex increased up to that of the control groups, after being markedly reduced in VPA-treated groups. GFAP immunoreaction was also improved against the strong positive gliosis detected in VPA-treated groups. CONCLUSIONS: The present study confirmed the protective role of folic acid against the cerebellar neurotoxic effects of VPA prenatal exposure. It is recommended that folic acid supplements should be given to every epileptic pregnant mother treated with VPA. (Folia Morphol 2018; 77, 2: 201-209).

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

STUDY QUESTION: In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? SUMMARY ANSWER: A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. WHAT IS KNOWN ALREADY: Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. STUDY DESIGN, SIZE, DURATION: This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. MAIN RESULTS AND THE ROLE OF CHANCE: Ongoing pregnancy rate was 12.8% (25/195) for mild ovarian stimulation versus 13.6% (27/199) for conventional ovarian stimulation leading to a risk ratio of 0.95 (95% CI: 0.57-1.57), representing an absolute difference of -0.7% (95% CI: -7.4 to 5.9). This 95% CI does not extend below the predefined threshold of 10% for inferiority. The duration of ovarian stimulation was significantly lower in the mild ovarian stimulation strategy than in the conventional ovarian stimulation strategy (mean difference -1.2 days, 95% CI: -1.88 to -0.62). Also, a significantly lower amount of gonadotropins was used in the mild simulation strategy, with a mean difference of 3135 IU (95% CI: -3331 to -2940). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study was the lack of data concerning the cryopreservation of surplus embryos, so we are not informed on cumulative pregnancy rates. Another limitation is that we were not able to follow up on the ongoing pregnancies in all centers, so we are not informed on live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: The results are directly applicable in daily clinical practice and may lead to considerable cost savings as high dosages of gonadotropins are not necessary in women with poor ovarian reserve undergoing IVF. A health economic analysis of our data planned to test the hypothesis that mild ovarian stimulation strategy is more cost-effective than the conventional ovarian stimulation strategy is underway. STUDY FUNDING/COMPETING INTERESTS: This study was supported by NUFFIC scholarship (the Netherlands) and STDF short-term fellowship (Egypt). TRIAL REGISTRATION NUMBER: NTR2788 (Trialregister.nl). TRIAL REGISTER DATE: 01 March 2011. DATE OF FIRST PATIENT'S ENROLMENT: May 2011.

The occurrence of maedi-visna virus in Lebanon.

Maedi-visna (MV) is a chronic viral disease prevalent in adult sheep that is caused by a virus belonging to the small ruminant lentivirus group (SRLV). This disease is considered to affect the international trade of sheep and is classified in the World Organisation for Animal Health (OIE) list of notifiable animal diseases. Although maedi-visna virus (MVV) has been detected in many countries, no study on its occurrence has been carried out in Lebanon. For this purpose, a serological survey of infection with MVV was conducted in seven of the eight Lebanese governorates using a competitive enzyme-linked immunosorbent assay (ELISA). A total of 184 individual blood samples from sheep of the local breed 'Awassi', originating from 16 farms distributed throughout the seven Lebanese governorates, were collected and analysed. Among the 184 tested sheep, 131 sheep from the16 farms visited were MVV positive. This presents a prevalence of 71% MVV-positive animals and 100% MVV-positive farms. The results indicate the need for further systematic investigations into the between-herd and within-herd prevalence of MV in Lebanon.

Le maedi-visna (MV) est une maladie virale chronique causée par un virus appartenant au groupe des lentivirus des petits ruminants (SRLV) et affectant les moutons adultes. La maladie a une incidence sur les échanges internationaux d'ovins et figure sur la liste des maladies à déclaration obligatoire de l'Organisation mondiale de la santé animale (OIE). La présence du virus maedi-visna est attestée dans de nombreux pays mais jusqu'à présent aucune étude ne lui avait été consacrée au Liban. Pour y remédier, une enquête sérologique recourant à une épreuve immuno-enzymatique (ELISA) par compétition a été conduite dans sept des huit gouvernorats du Liban afin de déterminer la prévalence de l'infection par le virus maedi-visna. Au total, 184 échantillons sanguins prélevés sur des moutons de race locale (Awassi) originaires de 16 élevages répartis dans les sept gouvernorats ont été analysés. Des résultats positifs ont été obtenus sur 131 des 184 prélèvements ; tous les élevages étaient représentés. La prévalence est donc de 71 % à l'échelle des individus et de 100 % à l'échelle des élevages. Il ressort de ces résultats que la prévalence à l'intérieur des élevages ainsi que celle entre élevages devraient faire l'objet d'enquêtes systématiques plus poussées au Liban.

El maedi-visna (MV) es una enfermedad viral crónica prevalente en ovejas adultas, cuyo agente etiológico es un virus del grupo de los lentivirus de los pequeños rumiantes. Figura en la lista de enfermedades de declaración obligatoria de la Organización Mundial de Sanidad Animal (OIE) porque se considera que afecta al comercio internacional de ovejas. Aunque el virus maedi-visna (VMV) ha sido detectado en muchos países, nunca antes se había estudiado su presencia en el Líbano. Para ello se llevó a cabo un estudio serológico de la infección por el virus en siete de los ocho distritos administrativos del país mediante un ensayo inmunoenzimático (ELISA) de competición. Se extrajeron y analizaron un total de 184 muestras sanguíneas de ovejas de la raza autóctona «awassi¼ procedentes de 16 explotaciones repartidas en los siete distritos libaneses. De esas 184 muestras, dieron resultado positivo para el VMV 131, correspondientes a ovejas de las 16 explotaciones visitadas. Ello supone una prevalencia del 71% de animales positivos al virus y del 100% de explotaciones positivas. Los resultados ponen de manifiesto la necesidad de investigar más sistemáticamente la prevalencia del maedi-visna entre los rebaños y dentro de los rebaños del Líbano.

Short communication: Pilot study on hormonal, metabolic, and behavioral stress response to treatment of claw horn lesions in acutely lame dairy cows.

Short-term effects of therapeutic claw trimming in acutely lame cows (n=21) with nonadvanced claw horn lesions on the endocrine, metabolic, and behavioral stress responses were investigated in comparison to regular claw trimming in nonlame control cows (n=21). Controls were matched to lame cows by parity and stage of lactation. Lame cows suffering from typical sole ulcers or white line disease were blinded and randomly assigned to 2 treatments, receiving 15 min before interventions either ketoprofen (n=11; 3mg/kg of BW intramuscularly; Romefen, Merial, Lyon, France) or placebo (n=10; saline in equivalent amount and route of administration). All cows underwent functional claw trimming in lateral recumbency on a surgical tipping table, and claw horn lesions in lame cows were conventionally treated (removal of loose horn, block on opposing claw, bandaging of affected claw). Blood samples collected 15 min before, at the end, and 24h after claw trimming were analyzed for concentrations of cortisol, fatty acids, lactate, and glucose, and fecal samples (collected before treatment and after 24 h) for cortisol metabolites. Behavioral stress responses during functional and therapeutic claw trimming were recorded. Concentrations of blood cortisol, fatty acids, glucose, and fecal cortisol metabolites were higher in lame than in nonlame cows after treatment. During claw treatment, more leg movements were recorded for lame cows than nonlame cows. Pre-emptive administration of ketoprofen had no obvious effects on stress responses to therapeutic claw trimming. Treatments of claw horn lesions caused a significant stress and pain reaction in acutely lame cows, demonstrating the necessity of adequate pain management protocols for such interventions.

Ageing and intergenerational family ties in Arab countries.

This paper explores the dominant issues in intergenerational ties in Arab countries with a view to highlighting patterns, trends and challenges as well as policy implications. The data were drawn from a review of scholarly work and published literature in Arab countries and from a regional mapping of ageing policies and programmes in 2012. Social and health ageing policies in the region have been set with the premise that the family represents the core safety net for older Arabs. Yet demographic, sociocultural and economic transitions, as well as political conflict in the Arab world, are bringing profound changes to familial structures. This review feeds into efforts to promote health and social reforms that approach intergenerational solidarity from several fronts: providing equitable old-age income security, fostering cross-generational interactions, embracing caregivers and home-based care, promoting age-responsive actions in emergencies and conflicts, and prioritizing context- and country-specific research on the levels, types and trends in intergenerational and familial support.

Caprine arthritis encephalitis virus: prevalence and risk factors in Lebanon.

An epidemiological survey, accompanied by a serological analysis,was conducted on samples taken from Lebanese goat herds in order to determine the prevalence of infection with the caprine arthritis encephalitis virus (CAEV) in Lebanon. The results of the survey provided information on various livestock production, animal health and herd management factors. Serum samplesfrom 952 goats, including the local breeds (Baladi and Damascene) and imported breeds (Alpine and Saneen), were taken from 60 farms distributed throughout Lebanon and tested for the presence of anti-CAEV antibodies. The data obtained were analysed using a statistical model to assess CAEV infection risk factors in Lebanon. In total, 125 samples proved to be positive, representing a prevalence in selected individuals of 13.1% and in selected herds of 51.7%. The Bekaa region had the highest number of herds with seropositive goats (90% of herds); the level was lower in Mount Lebanon, the North and the South (54%, 34% and 33%, respectively). The prevalence in relation to the livestock production system was 70% in herds in intensive systems, 54% in semi-intensive systems and 45% in extensive systems. The indigenous breeds were more resistant and tolerant of CAEV than the imported breeds. This study confirms the presence of CAEV in Lebanese goat herds and identifies the different livestock production practices likely to favour the rapid spread of the virus.

Efficiency of selenium in attenuating epididymal histopathological changes in hypercholesterolaemic adult rat.

BACKGROUND: Studies on sperm maturation, epididymal histology, or epididymal tubule physiology are significant parts in reproductive researches. The present study was aimed to evaluate the effect of induced hypercholesterolaemia on the epididymis of adult albino rats and to clarify the possible protective role of selenium. MATERIALS AND METHODS: Forty adult albino Wistar rats were divided into four groups; untreated control group (group I), sham control (group II), group with induced hypercholesterolaemia (group III), group with induced hypercholesterolaemia treated with selenium 0.25 mg/kg/day (group IV). RESULTS: Histological and ultrastructural examination of the epididymal epithelial cells of hypercholesterolaemic rats (group III) showed loss of cilia with many vacuolations, fatty degenerative changes and increased collagen fibres. Morphometrically significant increase (p < 0.0001) in the per cent area of collagen fibres with no significant change in the optical density of periodic acid Schiff reaction (p > 0.05). Selenium treated group (group IV) produced marked improvement in histological, ultrastructural and morphometric results as compared with group III. CONCLUSIONS: It could be concluded that hypercholesterolaemia produced deleterious effects to the epididymis and selenium could attenuate these effects.

Effectiveness of Calcium Hydroxide and Gingerols Mixture as a Novel Obturation Material for Infected Root in Primary Teeth: A Randomized Clinical Trial.

Introduction: The tendency to use dental materials of plant origin is one of the prevailing trends in dentistry to reduce exposure to materials that could have some toxic impact in the long term. Objective: To evaluate the efficacy of calcium hydroxide combined with gingerols (Ginge-Cal) as a novel obturation material for treating infected primary teeth and decreasing the recurrence of infection. Materials and Methods: The study was conducted on 30 lower primary molars with infected pulp for children aged 4-8 years. The sample was randomly divided into two groups depending on the tested obturation material: Ginge-Cal group and the Metapex group. The evaluation was done by different parameters clinically and radiographically at various intervals up to 12 months. Results: Based on chi-squared and McNamara's test with a 5% significance level, the clinical results indicated that Ginge-Cal group was more effective than the Metapex group in reducing or eliminating pain (P=0.467) after 1 week, sensitivity to percussion (P=0.090) at 3 months of follow-up, purulent swelling (P=0.444) at 6 and 9 months of follow-up, fistula, and tooth mobility. The radiographic results, based on the periapical and furcation area radiolucency at 12 months of follow-up, favored Ginge-Cal group over the Metapex group (P=0.683), (P=0.456), respectively. There were no statistically significant differences in pathological root resorption and periodontal space. The differences within the Ginge-Cal group were directly influenced by the time intervals in a statistically significant manner, ranging from (P=0.004) to (P < 0.001). The success percentage was 87.5% for Ginge-Cal group and 64.3% for Metapex group. Conclusions: Ginge-Cal can be considered a promising material for treating the infected root canal when used as an obturation material for the infected root canal. This trial is registered with NCT05181813.

Clinical Evaluation of Different Designs of Fixed Space Maintainer: A Randomized Clinical Trial.

Purpose: Evaluation of survival rates for three space maintainers (SMs) of different designs compared to the standard one. Materials and methods: A total of 52 extraction sites in children aged 4-7 years with prematurely lost primary molars were selected for this study. The whole sample was divided into four groups of 13 each. In group I, Band and Loop (B&L); group II, single-sided Band and Loop (Ss B&L); group III, Direct Bonded Wire (DBW); and group IV, Tube and Loop (T&L). Children were recalled at 3, 6, 9, 12, and 15 months. Cumulative survival rates of SMs were estimated using the Kaplan-Meier method with a logrank test. Results: Although there was a nonsignificant difference in the number of failed cases among all groups, the overall survival rate for group I was 69.2%, group II was 53.8%, group III was 38.5%, and group IV was 30.8% at the end of the study. The failure types for B&L were solder breakage (75% of the total failure rate) and cement dissolution (25%); for Ss B&L, they were solder breakage with lost loop (50%), soft tissue impingement (33%), and dislodgment (17%); for DBW, they were composite-wire interface debonding (75%) and enamel-composite interface debonding (25%); and finally, for T&L, they were lost T&L (56%), soft tissue impingement (22%), and total loss (22%). Conclusion: Banded SMs survived for a longer time than bonded ones, with superior performance for B&L compared to Ss B&L. In addition, bonded SMs required strict isolation conditions. DBW could be used in the maxilla rather than the mandible and was preferable for older children. How to cite this article: Hemdan ME, H El Kalla IHH, El Agamy RA. Clinical Evaluation of Different Designs of Fixed Space Maintainer: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2024;17(4):442-450.

Postoperative analgesic efficacy of meloxicam in lame dairy cows undergoing resection of the distal interphalangeal joint.

The objective was to evaluate the analgesic efficacy of pre- and postoperative administration of meloxicam on the postsurgical convalescence period of lame dairy cows undergoing resection of the coffin joint. In a blinded, placebo-controlled, explorative clinical trial, 19 lame German Holstein-Friesian cows weighing 536 ± 98 kg (mean ± SD) and aged 5.7 ± 2.8 yr were included. All cows suffered from unilateral lameness due to septic arthritis of the coffin joint. Lame cows were randomly allocated to either the meloxicam group (n=9) or the control group (n=10) and received an intravenous injection of meloxicam (0.5mg/kg of BW) or an equal volume of saline immediately before surgery (d 0) and once daily from d 1 to 4. All cows received a retrograde intravenous local anesthesia (20 mL of procaine 2%) before the surgical intervention. Heart rate, respiratory rate, body temperature, plasma concentrations of cortisol, as well as production parameters (milk yield and feed intake) were evaluated from d 0 to 7. The gait of the animals was assessed daily by lameness scores and by monitoring the cows' activity by means of pedometers attached to both hind legs. Possible adverse effects on abomasal mucosal integrity were monitored by fecal occult blood tests and blood cell counts from d 0 to 7 and on d 14. Under meloxicam treatment plasma cortisol levels, lameness scores, and body temperature were significantly reduced compared with controls. While being treated with meloxicam, the time cows were standing per day was significantly longer compared with controls. In the healthy limb significantly more steps were registered in meloxicam-treated cows than in controls. Feed intake and milk yield were not significantly affected by meloxicam. No group differences were found in number of positive tests for fecal occult blood or blood cell counts. In conclusion, repeated meloxicam application demonstrated effective analgesia in the postsurgical period after resection of septically infected coffin joints in dairy cows without indications of evoking adverse effects on abomasal integrity.

Effect of adhesive resin application on the progression of cavitated and non-cavitated incipient carious lesions.

PURPOSE: To evaluate the penetration of two different adhesive resin systems into cavitated and non-cavitated artificial carious lesions and the behavior of treated carious lesions under further acid attack. METHODS: Artificial caries-like lesions were created on the proximal surface of 100 human primary molars by a demineralizing gel. The teeth were assigned to three groups according to the adhesive resin used. Group 1 (G1) was for Single Bond adhesive resin, Group 2 (G2) for Xeno V adhesive resin, and Group 3 (G3) was without any adhesive application. Each group was randomly and equally subdivided into subgroups a and b. In subgroup a, the teeth were kept with intact artificial caries-like lesion surfaces while in the subgroup b, a minute cavity was made at the center of artificial caries-like lesions using a sharp explorer. Each tooth was sectioned occluso-cervically into two halves through the center of the lesion; the sectioned surface was polished and examined under a reflected light microscope for estimating the depth of the carious lesion or penetration of the adhesive resin. All tooth halves were coated at the sectioned surface with two layers of acid resistant nail varnish and returned again to the demineralizing solution to assess the progression or arrest of the carious lesion after the second acid attack. RESULTS: The penetration depth of adhesive resins did not differ significantly between subgroups (P>0.05). After the second acid attack, the infiltrated carious lesions showed no lesion progression while the non-infiltrated lesions showed advanced caries progression.

Cell-type diversity in the bed nucleus of the stria terminalis to regulate motivated behaviors.

Over the past few decades, the bed nucleus of the stria terminalis (BNST) gained popularity as a unique brain region involved in regulating motivated behaviors related to neuropsychiatric disorders. The BNST, a component of the extended amygdala, consists of a variety of subnuclei and neuronal ensembles. Multiple studies have highlighted the BNST as playing a fundamental role in integrating information by interfacing with other brain regions to regulate distinct aspects of motivated behaviors associated with stress, anxiety, depression, and decision-making. However, due to the high molecular heterogeneity found within BNST neurons, the precise mechanisms by which this region regulates distinct motivational states remains largely unclear. Single-cell RNA sequencing data have revealed that the BNST consists of multiple genetically identifiable cell-type clusters. Contemporary tools can therefore be leveraged to target and study such cell-types and elucidate their precise functional role. In this review, we discuss the different subsets of neurons found in the BNST, their anatomical distribution, and what is currently known about BNST cell-types in regulating motivated behaviors.

[Cortisol concentrations in sheep before, during and after sham foot trimming on a tilt table - the suitability of different matrices]. / Kortisolkonzentrationen bei Schafen vor, während und nach der simulierten Klauenbehandlung im Kippstand ­ Eignung verschiedener Matrices.

INTRODUCTION: Matrices that can be collected non-invasively for quantification of a stress response in sheep have received little attention in the veterinary literature. This study examines the suitability of blood, tears and saliva for determining a stress response in sheep undergoing sham foot trimming on a tilt table. The cortisol concentration of blood, tears and saliva and the concentration of cortisol metabolites in faeces were measured in 13 healthy Meat Merino ewes once a day for six days. Sham foot trimming on a tilt table was used as the stressor and was done during a one-hour period on day 4; cortisol concentrations of blood and tears were measured at 0, 10, 20, 30, 40 and 60 minutes. Cortisol concentrations of blood (maximum at 30 minutes) and tears (maximum at 40 minutes) increased during the procedure and then decreased. There were significant correlations between cortisol concentrations of blood and tears (p = 0,04) during sham foot trimming (area under the curve, 0 to 60 minutes). Over the entire 6-day study period, significant correlations were seen between the cortisol concentrations of blood and tears (r = 0,55; p.

INTRODUCTION: Les marqueurs qui peuvent être collectés de manière non invasive pour quantifier une réponse au stress chez le mouton ont fait l'objet de peu d'attention dans la littérature vétérinaire. Cette étude examine la pertinence du sang, des larmes et de la salive pour déterminer une réponse au stress chez des moutons subissant un parage fictif des pieds sur une table basculante. La concentration de cortisol dans le sang, les larmes et la salive ainsi que la concentration de métabolites de cortisol dans les fèces ont été mesurées chez 13 brebis Meat Merino saines une fois par jour pendant six jours. Le parage fictif des pieds sur une table inclinable a été utilisé comme facteur de stress et a été effectué pendant une période d'une heure le jour 4; les concentrations de cortisol dans le sang et les larmes ont été mesurées à 0, 10, 20, 30, 40 et 60 minutes. Les concentrations de cortisol dans le sang (maximum à 30 minutes) et les larmes (maximum à 40 minutes) ont augmenté au cours de la procédure puis ont diminué. Il y avait des corrélations significatives entre les concentrations de cortisol dans le sang et les larmes (p = 0,04) lors du parage fictif des onglons (aire sous la courbe, 0 à 60 minutes). Sur l'ensemble de la période d'étude de 6 jours, des corrélations significatives ont été observées entre les concentrations de cortisol dans le sang et les larmes (r = 0,55 ; p < 0,001), le sang et la salive (r = 0,53 ; p < 0,001) et les larmes et la salive (r = 0,78 ; p < 0,001). La concentration fécale de métabolites de cortisol était significativement augmentée au jour 5 (p 0,05), mais la concentration de cortisol des autres supports n'a pas changé de manière significative au cours de la période d'étude de 6 jours. Le parage fictif des pieds sur une table basculante a été considéré comme un facteur de stress aigu chez les moutons en raison de l'augmentation des concentrations de cortisol dans le sang, des larmes et de l'augmentation des concentrations de métabolites de cortisol dans les selles. La concentration de cortisol dans les larmes était similaire à celle du sang et, par conséquent, la collecte de larmes représente une alternative viable et non invasive au sang pour les tests de cortisol. Le délai des pics entre la concentration maximale de cortisol dans les larmes et le sang doit être pris en compte lors de l'interprétation des résultats.

Association of Apolipoprotein E gene polymorphism with the risk of T2DM and obesity among Egyptian subjects.

BACKGROUND: Numerous reports investigated the involvement of apolipoprotein E (APOE) polymorphisms with elevated risk of type 2 diabetes mellitus (T2DM) and obesity. The principal objective of this study is to assess the contribution of APOE polymorphisms (rs429358 and rs7412) with the risk of T2DM and obesity. SUBJECTS AND METHODS: This work was designed involving 400 participants [100 healthy controls, 100 T2DM patients, 100 obese patients, and 100 T2DM + obese patients]. Genomic deoxyribonucleic acid (DNA) of the APOE polymorphisms was characterized using the PCR-RFLP assay. RESULTS: The common predominant genotype of the study population is the APOE Ɛ3/Ɛ3 [T2DM patients (46%), obese patients (52%), T2DM + obese patients (37%), and healthy controls (58%)]. The frequencies of the APOE Ɛ4/Ɛ4 genotype and the APOE*Ɛ4 allele were significantly elevated among T2DM patients (p-value < 0.05). Additionally, the frequencies of the APOE Ɛ2/Ɛ2 genotype and the APOE*Ɛ2 allele were significantly increased among obese patients (p-value < 0.05). Moreover, the frequencies of the APOE Ɛ2/Ɛ2 genotype, APOE*Ɛ2 allele, APOE Ɛ4/Ɛ4 genotype, and APOE*Ɛ4 allele were statistically significant among T2DM + obese patients (p-value < 0.05). CONCLUSIONS: APOE*Ɛ2 and APOE*Ɛ4 alleles were considered as independent risk factor among T2DM + obese patients. Furthermore, the APOE*Ɛ2 allele was correlated with elevated risk of obesity, while the APOE*Ɛ4 allele was correlated with elevated risk of T2DM.

Efficacy of erythropoietin-pretreated mesenchymal stem cells in murine burn wound healing: possible in vivo transdifferentiation into keratinocytes.

BACKGROUND: Stem cells have shown promising potential to treat burn wounds. Erythropoietin was capable of promoting in vitro transdifferentiation of mesenchymal stem cells (MSCs). The aim of the study was to investigate possible role of erythropoietin-pretreated mesenchymal stem cells (EPOa/MSCs) in burn wounds healing and to evaluate its in vivo differentiation into keratinocytes. MATERIALS AND METHODS: Forty rats were utilised in this study divided into four groups (n = 10 for each). Control group (I), burn group (II), burn + MSCs, group (III), burn + EPOa/MSCs. 1 × 106 cells were injected locally for each 1 cm² of burn areas. Burn areas were followed-up morphologically. After 21 days of the experiment, the rats were euthanised, skin specimens were assessed biochemically, histologically and immunohistochemically. RESULTS: EPOa/MSCs enhanced significantly (p < 0.05) burn wound vimentin gene expression and level of interleukin (IL)-10 while decreased IL-1 and COX2 as compared to the burn group. Histologically, EPOa/MSCs improved epithelialisation despite stem cells' differentiation into keratinocytes was rarely detected by PKH26 red fluorescence. EPOa/MSCs promoted angiogenesis as detected by significant increase in VEGF and PDGF immunoexpression as compared to burn group. CONCLUSIONS: EPOa/MSCs may improve burn wound healing, probably through anti-inflammatory, immunomodulatory and angiogenic action. However, in vivo transdifferentiation into keratinocytes was rarely detected.

Dose-dependent effect of romifidine on intraocular pressure in clinically healthy buffalo (Bubalus bubalis).

In the present study, changes in intraocular pressure (IOP) associated with romifidine sedation in buffalo were evaluated. Eighteen healthy adult, non-pregnant, buffalo without ocular abnormalities were used in a prospective randomized trial. Buffalo were allocated into three groups (six each). Buffalo in the treated groups received an intramuscular injection (IM) of romifidine at 40 or 50 µg/kg. The control group was administrated an equivalent volume of sterile saline (0.9% NaCl; 0.4 ml/100 kg). Baseline IOP (T0) values were obtained using applanation tonometry. Immediately afterwards, romifidine was administered and IOP values of both eyes were measured at 5, 15, 30, 45, 60, 90, 120, and 180 min post-administration. The pre-administration values (T0) of IOP for both the left and right eyes ranged from 30-36 (mean, 33 ± 1.5) mmHg and 30-35 (mean, 33.7 ± 1.4), respectively. IOP values decreased significantly after administration of both doses of romifidine compared with the placebo (P < 0.01). Compared with the control, the IOP decreased significantly in animals treated with both doses from 5-90 min post-administration in both eyes (P < 0.05). In the right eye, the lowest IOP value in the romifidine treated groups was observed at T30 (21.6 ± 1.0 and 23.3 ± 1.4 mmHg), respectively. In the left eye, the lowest IOP was observed at T60 (22.5 ± 3.0 and 23.3 ± 2.8 mmHg), respectively. In conclusion, romifidine could be recommended as an alternative analgesic in buffalo, especially for ocular affections associated with increased IOP. A dose of 40 µg/kg could be used at a low cost.

Effects of nicotine on rat adrenal gland: crosstalk between oxidative and inflammatory markers, and amelioration by melatonin.

Although the risks of smoking are well known, the effects of exposure to nicotine on endocrine functions remain unclear. We investigated the deleterious effects of nicotine on the adrenal gland and the mechanisms of these changes in rats. The role of melatonin in ameliorating pathological changes also was investigated. We used 24 rats divided into four groups of six: group 1, control; group 2, nicotine treated; group 3, nicotine and melatonin treated; group 4, melatonin treated. We used histology; immunohistochemistry of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and tyrosine hydroxylase (TH); measured oxidative and antioxidative markers, malondialdehyde (MDA) and glutathione (GSH); and performed real-time PCR for NF-κB 65, IL1-B and IL6. We also performed histomorphometric analysis. Indentation and lamellar separation of the adrenal capsule, vacuolated degenerated cells and lymphocytic infiltration were observed in group 2. Vacuolated cells and cells with pyknotic nuclei also were detected in the zona reticularis and medulla of the same group. We observed improved shape and cellular lining of the gland in groups 3 and 4. Widespread expression of iNOS, VEGF and TH, increased area percent collagen, decreased GSH (56%) and increased MDA, NF-κB, IL1-B and IL-6 were observed in group 2. All parameters were ameliorated in groups 3 and 4. The effects of nicotine on the adrenal gland can be attributed to oxidative and inflammatory stress; melatonin ameliorates these effects.

Single-cell activity tracking reveals that orbitofrontal neurons acquire and maintain a long-term memory to guide behavioral adaptation.

Learning to predict rewards based on environmental cues is essential for survival. The orbitofrontal cortex (OFC) contributes to such learning by conveying reward-related information to brain areas such as the ventral tegmental area (VTA). Despite this, how cue-reward memory representations form in individual OFC neurons and are modified based on new information is unknown. To address this, using in vivo two-photon calcium imaging in mice, we tracked the response evolution of thousands of OFC output neurons, including those projecting to VTA, through multiple days and stages of cue-reward learning. Collectively, we show that OFC contains several functional clusters of neurons distinctly encoding cue-reward memory representations, with only select responses routed downstream to VTA. Unexpectedly, these representations were stably maintained by the same neurons even after extinction of the cue-reward pairing, and supported behavioral learning and memory. Thus, OFC neuronal activity represents a long-term cue-reward associative memory to support behavioral adaptation.

The use of cerclage wire for surgical repair of unilateral rostral mandibular fracture in horses.

Fractures of the rostral mandible in horses are the most common type of jaw fractures. The present study was performed for stabilization of rostral mandibular fracture with cerclage wire. In a retrospective case series, six client-owned horses with unilateral mandibular fractures were admitted to our clinic and suffered from a major gingival wound at rostral part of mandible. Rostral mandibular fracture was diagnosed through clinical examination and radiography. Fractured region was repaired by cerclage wire under the effect of general anesthesia and wires were maintained for 6-12 weeks. The repair of mandibular fracture by cerclage wiring exhibited good fracture reduction and fixation in five horses and fair results in one horse. After twelve weeks, the fracture healing was excellent practically and cosmetically. Furthermore, the horses appeared normal without any evidence of teeth-related mastication problems, obstinate fracture-site fistula, or extreme callus formation. Radiographically, cerclage wire achieved good fracture fixation and fracture gap closure. Moreover, the formation of uniting callus was noticed at 6-12 weeks post-operatively. It was concluded that, unilateral mandibular fracture in horses can successfully be repaired by interdental wiring (IDW). All horses were returned to their usual activities without any fracture healing-related masticatory problems at the time of follow-up.