Proper post-partum reproductive performance is important for reproductive efficiency in beef cows, and dystocia decreases post-partum fertility. Crossbred beef cows (n = 1676) were evaluated for lifetime performance based on degree of dystocia at presentation of the first calf. Cows that experienced moderate or severe dystocia produced fewer calves during their productive life (P < 0.01). The exact mechanism is unclear, but may be due to the contributions of dystocia to abnormal placental separation. Proteolytic activity is hypothesized to contribute to placental separation in ruminants; however, when ovine placentomes were collected following caesarian section, no proteolytic activity was detected. We hypothesized that stage 2 of parturition was necessary to stimulate proteolysis and initiate placental separation. Serial placentome collections were performed on mature cows (n = 21 initiated; 7 with complete sampling) at hourly intervals for the first 2 h after expulsion of the calf. An intact piece of each placentome was fixed for histological evaluation, and a separate piece of caruncular and cotyledonary tissue from each placentome was frozen for transcriptomic and proteolytic analysis. A full set of placentomes was collected from only 7 of 21 cows at 0, 1, and 2 h, and all cows had expelled fetal membranes by 6 h. Histological, transcriptomic and proteolytic analysis was performed on placentomes from cows from which three placentomes were collected (n = 7). The microscopic distance between maternal and fetal tissues increased at 1 h (P = 0.01). Relative transcript abundance of matrix metalloprotease 14 (MMP14) tended to increase with time (P = 0.06). The relative transcript abundance of plasminogen activator urokinase-type (PLAU) was greater in caruncles than cotyledons (P = 0.01), and tended (P = 0.10) to increase in the caruncle between 0 and 2 h while remaining unchanged in the cotyledon over the same span of time. Greater PLAU and plasminogen activator tissue-type (PLAT) proteolytic activity was detected by zymography in the caruncle than the cotyledon immediately post-partum (P < 0.01). From these findings we conclude that 1) dystocia during the first parity decreases lifetime productivity in beef cattle, 2) the PA system is present at both the transcript and protein level in the bovine plactentome during parturition and 3) proteolytic activity is localized to the caruncular aspect of the placentome.

Action of Cisplatin (cis-dichlorodiammine platinum II) and Poly-Plat [poly-[(trans-1,2-diaminocyclohexane) pla-tinum]-carboxyamylose] on tumor cells was examined using human fibrosarcoma (HT1080) and Walker rat carcinoma (WRC-256) in culture. These cells were treated with Poly-Plat (10 microg/ml) or Cisplatin (10 mg/ml) for 2-5 days. Peritoneal macrophages were treated with Cisplatin (10 microg/ml) or Poly-Plat (10 microg/ml) for 2 hours and allowed to grow in normal medium for 48 hours. Supernatants from treated macrophages were collected at 0, 4, 12, 24 and 48 hours and IL-2 levels were examined using ELISA technique. The cytotoxicity of these supernatants was examined using HT1080 and WRC-256 cells. Apoptotic assays were used to determine the cytotoxic effects of drugs and macrophage supernatants on tumor cells. These results demonstrate the ability of Poly-Plat to arrest the growth of tumor cells and activate macrophages to induce apoptosis in the cell lines tested.

In this study the bark of Acacia modesta was evaluated for anti-inflammatory, antipyretic, analgesic, antidepressant and anticoagulant activity by carrageenan, hot plat, forced swim and capillary tube method respectively in rats. Highest anti-inflammatory activity was exhibited by chloroform (AMC) extract (74.96% inhibition) while other two active fractions being n-hexane (AMH) and ethyl acetate (AME) exhibited 71.26% and 52.87% inhibition of edema respectively. On the other hand, the aqueous (AMA) fraction showed most effective response with 67.06% analgesic activity. Additionally, the significant (p<0.05) post-treatment antipyretic effect was found by all fractions in time dependent manner. The current findings showed that AMC, AME and AMA had significant reduction in immobility time in the antidepressant test, while AMH showed mild antidepressant activity. In anticoagulant assay, the coagulation time of crude extract A. modesta and its all fractions were comparable to that of positive control aspirin (208s). Moreover, neither mortality nor lethality was observed in the tested animals. Overall, the plant extracts showed potent anti-inflammatory, antipyretic, analgesic, antidepressant and anticoagulant activities which concludes that the bark of A. modesta have significant therapeutic potential.

Estrogen decreasing during menopause can create problems in the cardiovascular organs, brain, urogental tract, and bone. Estrogen replacement therapy (ERT) can be used to increase estrogen levels. However, side-effects including breast cancer may limit their use. Tempe and tofu are natural plat-based foods which contain phytoestrogens. The aim of this research was to compare estrogen serum levels in ovariectomized rats given tempe flour and tofu flour. This research was conducted on female rats, aged 12 months (n = 72 rats). Rats were grouped into 5 groups: tempe flour, tofu flour, estradiol, casein and non-ovariectomized. The intervention was carried out for two months with three observation points; i) in the second week, ii) fifth week and iii) eighth week. Estrogen serum analysis was done by ELISA (Estradiol EIA-2693). The mean and the differences between treatment groups were analysed using one way ANOVA with post hoc polynomial contrasts (LSD). The highest estrogen serum in the second week intervention was found in the estradiol group followed by the tempe flour, tofu flour, non-ovariectomized and casein groups, respectively. The tempe flour group had the highest mean serum estrogen levels in the fifth week, followed by the estradiol group, non-ovariectomized group, tofu group and casein group. At the eighth week of intervention, the highest estrogen serum level was found in the tempe flour group followed by the estradiol group, tofu flour group, non ovariectomy group and casein group. Interventions in the fifth and eighth weeks showed significant differences between groups (p < 0.05). It was concluded that tempe flour rendered twice the serum estrogen level compared to tofu flour. Further research is needed in the form of clinical trials to prove that effect in humans.

Objectives: To evaluate the effectiveness and the frequency of use of a pulsed xenon ultraviolet light-emitting no-touch portable device (PX-UV), applied after perform current cleaning, in reducing environmental bacterial burden and the presence of pathogens on surfaces in the operating rooms at the Policlinico University Hospital of Foggia.

Design: Prospective before-and-after study with a follow up duration of four months, from May to August 2019.

Setting and participants: Two operating rooms of an Orthopaedic and a Neurosurgical ward in a 780-bed university hospital in the District of Foggia, Italy (about 600,000 inhabitants).

Main outcome measures: According to the hygienic standards proposed by the Italian Workers Compensation Authority (ISPESL), the total and the average bacterial load and the presence of six pathogens were evaluated between pre- and post- PX-UV use combined with routine manual cleaning.

Results: The PX-UV system was applied at five distinct time points: t1: start of the experiment, t2: after 28 days, t3: after 13 days, t4: after 7 days, and t5: after 8 days (t2-t5: 28 days in total). About 16-min of PX-UV cycle showed significant reduction in the level of environmental contamination by decreasing the mean colony count by 87.5%, compliant with the standard (5&lt; X ≤15 CFU per plat). Staphylococcus aureus and Acinetobacter baumannii that had been isolated in some of the samplings before PX-UV were no longer detected after t1, t2 and t5 treatments. Before PX-UV, the mean colony count was similar between t1 and t2 (p&gt;0.05); after t3 and t4 treatments, it was lower before t5 in both the Orthopaedic and Neurosurgical operating rooms (= -97% and -75%, respectively; p&lt;0,01).

Conclusions: Implication for practice: PX-UV could supplement the standard cleaning process in reducing the microbial burden in the operating rooms and potentially achieving lower healthcare-associated surgical site infections rates.

Introduction: In the past decades, the massive explosion of "Japanese" restaurants serving raw fish popularised new culinary habits in France. At the same time, consumers have made a habit of preparing raw or pickled fish dishes themselves at home. As a result, the identification of live parasitic worm larvae in raw fish flesh is common and a source of concern for professionals or amateur cooks. Sometimes, these worms are spit out or removed after fibroscopy in patients developing severe epigastric pain quickly after eating raw fish. This paper is aiming at having a quick review of the main parasites transmitted to humans by eating raw fish in France.

Methods: This article is based on the personal experience of the authors, on references preferentially from the French literature and on the results of the Fish Parasites (ANR) research program.

Results: From 2011 to 2014, Fish-Parasites (ANR) assessed the prevalence of parasitism in sea and freshwater fish belonging to 29 species. About 57% of sea fish were parasitised by Anisakidae. Larvae of Dibothriocephalus latus were found in pike, perch, and burbot in Lake Geneva but in none of the fish examined from Annecy or Le Bourget lakes. Concerning human anisakidosis, a retrospective survey was carried out in the years 2010 to 2014 among all medical parasitology laboratories from university hospitals in France. Thirty-seven cases of anisakidosis have been reported, including 18 cases of allergic anisakidosis. Six additional cases of severe Anisakidae allergy were reported to the National Allergovigilance Network over the same period.

Conclusions: Despite the increase in consumption of raw fish, and compared to previous studies, cases of anisakidosis are decreasing, but their allergenic potential is increasing. The incidence of dibothriocephalosis, after some trend of emergence on the shores of Lake Geneva some 20 years ago, is currently decreasing, but sporadic cases of importation are still reported. Actions with professionals (investigation, providing of information) and research programs on management of parasitic risk control are being pursued and have resulted in an update of the technical instruction of the French General Directorate for Food on the control of parasitic risk in fish.

Introduction: Il y a une vingtaine d’années l’explosion massive de restaurants « japonais » servant du poisson cru a popularisé de nouvelles habitudes culinaires en France. Parallèlement, les consommateurs ont pris pour habitude de préparer eux-mêmes, à domicile, des plats à base de poissons crus ou marinés. En conséquence, la mise en évidence de larves de vers parasites vivants dans la chair de poisson crue est fréquente et une source d’inquiétude pour les professionnels ou les cuisiniers amateurs. Parfois, ces vers sont recrachés ou extirpés après fibroscopie chez des patients ayant présenté de violentes douleurs épigastriques rapidement après consommation de poissons crus. L’objectif de cet article est de faire le point sur les principales parasitoses transmises à l’Homme par la consommation de poisson cru en France.

Méthodes: Cet article est basé sur l’expérience personnelle des auteurs, sur des références bibliographiques choisies préférentiellement dans la littérature française et sur les résultats du programme de recherche Fish Parasites (ANR).

Résultats: De 2011 à 2014, l’action Fish-Parasites (ANR) a évalué la prévalence du parasitisme chez des poissons de mer et d’eau douce appartenant à 29 espèces. Environ 57 % des poissons de mer étaient parasités par des Anisakidae. Des larves de Dibothriocephalus latus ont été retrouvées dans les brochets, perches et lottes du lac Léman, mais chez aucun des poissons examinés des lacs d’Annecy ou du Bourget. En ce qui concerne l’anisakidose humaine, une enquête rétrospective a été réalisée sur les années 2010 à 2014 auprès de tous les laboratoires hospitalo-universitaires de parasitologie de France. Trente-sept cas d’anisakidose ont pu être répertoriés dont 18 cas d’anisakidose allergique. Six cas supplémentaires d’allergie sévère aux Anisakidae ont été rapportés au réseau national d’allergovigilance sur cette même période.

Conclusions: Malgré l’augmentation de la consommation de poissons crus, et par rapport à des études antérieures, les cas d’anisakidose diminuent, mais leur potentiel allergisant est en augmentation. L’incidence de la dibothriocéphalose, après une certaine tendance à l’émergence sur les bords du lac Léman il y a une vingtaine d’années, est actuellement en diminution, mais des cas sporadiques d’importation sont toujours rapportés. Des actions auprès des professionnels (enquête, mise à disposition d’éléments d’information et de communication) et des programmes de recherche sur la maîtrise du risque lié aux parasites sont poursuivis et ont abouti à une mise à jour de l’instruction technique de la Direction générale de l’alimentation sur la maîtrise du risque parasitaire chez les poissons.

Keywords: Anisakidae; Anisakis; Dibothriocephalus latus; Raw fish.

Context: Some market populations in Nigeria have been shown to have high prevalence of hypertension. Current evidence includes environmental pollutants such as heavy metals as risk factors for hypertension.

Aim: To study the heavy metal content of rice meals sold in a market population with a high prevalence of hypertension.

Settings and design: This was a descriptive, cross-sectional study conducted in Ogbete market in Enugu, Southeast Nigeria.

Subjects and methods: Five different cooked rice meals were obtained from 25 locations of the market. The rice meals included jollof rice, white rice and tomato stew, fried rice, white rice and vegetable sauce, and white rice and palm oil stew (ofeakwu). Accompanying protein (meat, fish, and egg) and vegetable salad were excluded. Similar rice meals were homogenized and analyzed in triplicates using spectrophotometric methods for mercury, copper, cadmium, lead, and arsenic determination.

Statistical analysis used: The mean concentrations of the heavy metals were compared using analysis of variance, and P < 0.05 was considered statistically significant.

Results: Twenty-five rice dishes were evaluated, five of each kind. Arsenic content ranged from 503 to 550 mg/kg and was comparable across the five rice dishes (P = 0.148). Copper was significantly highest (16767 mg/kg) in the white rice and tomato stew dish (P < 0.001), while mercury was significantly highest (33 mg/kg) in white rice and ofeakwu (P < 0.001). Jollof rice had the highest cadmium content (23 mg/kg), which was statistically significant (P = 0.021). Lead was not found in any of the rice dishes.

Conclusions: Risk factors such as heavy metals may play a role in the high prevalence of hypertension observed in market populations, and rice meals may be a major source of these heavy metals.

Résumé Contexte: Il a été démontré que certaines populations du marché au Nigéria présentent une prévalence élevée d'hypertension. Les preuves actuelles incluent l'environnement des polluants tels que les métaux lourds comme facteurs de risque d'hypertension. Objectif: étudier la teneur en métaux lourds des farines de riz vendues dans une population de marché avec une prévalence élevée d'hypertension. Paramètres et conception: il s'agit d'une étude descriptive et transversale menée sur le marché d'Ogbete en Enugu, sud-est du Nigéria. Sujets et méthodes: Cinq plats de riz cuit différents ont été obtenus dans 25 emplacements du marché. Le riz les repas comprenaient du riz jollof, du riz blanc et du ragoût de tomates, du riz frit, du riz blanc et de la sauce aux légumes, et du riz blanc et du ragoût d'huile de palme (ofeakwu). Les protéines d'accompagnement (viande, poisson et œuf) et la salade de légumes ont été exclues. Des farines de riz similaires ont été homogénéisées et analysées triplicats utilisant des méthodes spectrophotométriques pour la détermination du mercure, du cuivre, du cadmium, du plomb et de l'arsenic. Analyse statistique utilisée: le les concentrations moyennes des métaux lourds ont été comparées à l'aide d'une analyse de variance, et P <0.05 a été considéré comme statistiquement significatif. Résultats: Vingt-cinq plats de riz ont été évalués, cinq de chaque type. La teneur en arsenic variait de 503 à 550 mg / kg et était comparable dans les cinq plats de riz (P = 0,148). Le cuivre était significativement plus élevé (16767 mg / kg) dans le plat de ragoût de riz blanc et de tomate (P <0.001), tandis que le mercure était significativement plus élevé (33 mg / kg) dans le riz blanc et l'ofeakwu (P <0.001). Le riz Jollof avait la plus forte teneur en cadmium (23 mg / kg), qui était statistiquement significatif (P = 0.021). Le plomb n'a été trouvé dans aucun des plats de riz. Conclusions: Des facteurs de risque tels que les métaux lourds peuvent jouent un rôle dans la prévalence élevée de l'hypertension observée dans les populations du marché, et les farines de riz peuvent être une source majeure de ces métaux lourds.

Keywords: Heavy metals; Nigeria; hypertension; rice.

'Poly-plat', SSP and SAP are second generation analogs of cisplatin which have been shown to activate murine peritoneal macrophages in vivo and in vitro. Murine peritoneal macrophages treated with 'poly-plat', SSP or SAP (5 microg/mg) for 2 h are stimulated to form cytoplasmic extensions. Drug-treated macrophages also elicit an increase in the number of lysosomes. In addition, analysis of tissue culture supernatants shows increased levels of interleukin-1alpha and tumor necrosis factor-alpha. These results show that 'poly-plat', SSP and SAP enhance the immune system with greater efficacy and potency than cisplatin.

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes, constitute a major medical challenge with a critical need for development of cell-based therapies. We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location-matched skin of diabetic patients and normal healthy donors and re-differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling. We found let-7c, miR-26b-5p, -29c-3p, -148a-3p, -196a-5p, -199b-5p and -374a-5p suppressed in iPSC-derived fibroblasts in vitro and in 3D dermis-like self-assembly tissue, whereas their corresponding targets involved in cellular migration were upregulated. Moreover, targets involved in organization of extracellular matrix were induced after fibroblast reprogramming. PLAT gene, the crucial fibrinolysis factor, was upregulated in iPSC-derived fibroblasts and was confirmed as a direct target of miR-196a-5p. miR-197-3p and miR-331-3p were found upregulated specifically in iPSC-derived diabetic fibroblasts, while their targets CAV1 and CDKN3 were suppressed. CAV1, an important negative regulator of wound healing, was confirmed as a direct miR-197-3p target. Together, our findings demonstrate that iPSC reprogramming is an effective approach for erasing the diabetic non-healing miR-mediated epigenetic signature and promoting a pro-healing cellular phenotype.

Keywords: diabetic foot ulcer; fibroblasts; iPSC; microRNA; reprogramming; skin.

Background: Cardiac resynchronization therapy (CRT) is a well-established treatment for patients with drug refractory heart failure OBJECTIVES: This study sought to compare the longest RVsense to LVsense activation time (sLAT) versus the longest RVpace to LVsense activation time (pLAT) as the programmed site for LV pacing in CRT patients with quadripolar LV leads at 3 months.

Methods: This single site, double-blinded, prospective trial, randomized patients 1:1 into the sLAT or pLAT group to determine response. Left ventricular pacing was programmed at implant and maintained thru 3 months of follow-up. The 6-minute hall walk test (6MHW), NYHA, MLWHF, and Clinical Composite Score (CCS) at the 3-months was compared.

Results: N = 92 patients (73M:19F age 66 ±11.3 years) were randomized implanted and programmed per protocol. Baseline characteristics were comparable. N = 39 sLAT and N = 34 pLAT completed the 3-month visit for final analysis. Significant improvement from baseline to 3 months was seen in the sLAT group from 253.9(+/-11.5) to 323.1(+/-11.9) P = 0.001 Similarly, the pLAT group improved from 274.9 (+/-16.15) to 343.9 (+/-15.9) p = 0.003. The difference between these groups however did not reach significance. (P = 0.86) The pLAT group demonstrated a higher responder rate of (71%) versus the sLAT group (64%) based on the CCS although not reaching significance (P = 0.56) CONCLUSIONS: Use of both the pLAT and sLAT method of programming demonstrated significant improvement in 6MHW distance at 3 months with pLAT demonstrating a slightly higher responder rate based on CCS (P = 0.56). pLAT should be considered at minimum as equivalent in patients with no intrinsic conduction. This article is protected by copyright. All rights reserved.

Keywords: CRT; Congestive Heart Failure; Optimization.

Background: Biallelic mutations in LOXHD1 have been identified as the cause of DFNB77 (deafness, autosomal recessive 77). It is a new progressive, severe-to-profound, and late-onset nonsyndromic sensorineural hearing loss (NSHL), and is highly heterogeneous genetically and phenotypically. This study aimed to provide an additional three cases of DFNB77.

Methods: We presented three unrelated children diagnosed with prelingual mild-to-severe NSHL, and their audiograms showed mild hearing loss at 250 Hz before downsloping to a moderate-to-severe degree. Trio whole-exome sequencing (WES) was conducted to identify the pathogenic variants. Additionally, we reviewed the literature to further analyze the relationships between the genotype and audiology phenotype of LOXHD1.

Results: Six novel possible pathogenic LOXHD1 variants were identified, including three missense, one nonsense, and two splicing variants. The literature review showed that 68.5% of patients with DFNB77 onset before five years old; Most variants (62%) were associated with a down-sloping audiogram of mild-to-moderate hearing loss at low frequencies (200Hz, 500Hz), particularly variants in the protein domain of PLAT 9. We found that compared with homozygous LOXHD1 variants, individuals with heterozygous compound variants had a significantly milder phenotype, especially individuals carrying one missense and one splicing or bi-allelic missense variants (P < 0.05). Audiometric analysis at different ages showed that the hearing loss degree was aggravated at all frequencies by increasing age.

Conclusions: We report three children with prelingual NSHL carrying six novel LOXHD1 variants. Furthermore, our work indicates that DFNB77 may be milder than previously reported and recommends considering the genotype combination and mutation location of LOXHD1 and race-specificity in DFNB77 molecular diagnoses and management.

Keywords: DNBF77; Genotype-phenotype correlations; Hearing loss; LOXHD1; Whole-exome sequencing.

Symbiotic nitrogen fixation by rhizobia in legume root nodules is a key source of nitrogen for sustainable agriculture. Genetic approaches have revealed important roles for only a few of the thousands of plant genes expressed during nodule development and symbiotic nitrogen fixation. Previously, we isolated >100 nodulation and nitrogen fixation mutants from a population of Tnt1-insertion mutants of Medigaco truncatula. Using Tnt1 as a tag to identify genetic lesions in these mutants, we discovered that insertions in a M. truncatula nodule-specific polycystin-1, lipoxygenase, α-toxin (PLAT) domain-encoding gene, MtNPD1, resulted in development of ineffective nodules. Early stages of nodule development and colonization by the nitrogen-fixing bacterium Sinorhizobium meliloti appeared to be normal in the npd1 mutant. However, npd1 nodules ceased to grow after a few days, resulting in abnormally small, ineffective nodules. Rhizobia that colonized developing npd1 nodules did not differentiate completely into nitrogen-fixing bacteroids and quickly degraded. MtNPD1 expression was low in roots but increased significantly in developing nodules 4 d postinoculation, and expression accompanied invading rhizobia in the nodule infection zone and into the distal nitrogen fixation zone. A functional MtNPD1:GFP fusion protein localized in the space surrounding symbiosomes in infected cells. When ectopically expressed in tobacco (Nicotiana tabacum) leaves, MtNPD1 colocalized with vacuoles and the endoplasmic reticulum. MtNPD1 belongs to a cluster of five nodule-specific single PLAT domain-encoding genes, with apparent nonredundant functions.

Glioma is one particular type of brain malignancy which is highly complex and usually has a poor prognosis. Despite the limited diagnostic level of glioma, the survival time of affected patients broadly varies. Here, we conducted a detailed analysis, regarding the differences in patient survival time, to discover potential survival-related genes in glioma as well as their putative regulatory mechanisms. To contextualize the acquisition of these potential prognosis markers in large populations, particularly in China, we combined CGGA and The Cancer Genome Atlas (TCGA) databases to properly identify genes that are significantly related to survival. Our workflow combined a series of analytical approaches, including differential analysis, survival time, co-expression, clinical correlation analysis, ROC curve evaluation and prediction ability. Our results indicate that the four particular genes - PLAT, IGFBP2, BCAT1, SERPINH1 could be used as independent prognostic marker genes. These genes have also shown good prognostic ability in distinct populations, reiterating the robustness and value of these prognostic markers.

Keywords: Glioma; clinical correlation analysis; prognostic marker gene; survival analysis.

Vinclozolin (VCZ) is a fungicide with antiandrogen activity. Exposure to VCZ in maternal uterus may cause uterine, ovarian and testicular damage, hypospadias and prostate abnormality in the offspring. Hippo pathway, which is highly conservative and may be activated by miR132 and miR195a, can control organ size and tissue regeneration, and participate in injury and deformity. In the present study, VCZ was found to have caused penile malformation in the male offspring and also induced "small testis" when it was administered to the pregnant mice orally at a dose of 400 mg kg^-1 day^-1 on Days 12-18 of gestation. At 1, 3 and 7 weeks of age, VCZ could increase miR132, Mst1, Sav1, phosphorylated Yes-associated protein (pYap) and pLats, and decrease Yap in offspring penises and testes. Besides, it could also raise miR195a both in the testes of 1, 7-week and in the penises of all the three ages. In addition, we found the levels of some cyclin (Ccn) genes elevated in the tests, the expression of the androgen receptor (Ar) gene dereased and Jnks changed in the penises of offspring aged 1, 3 and 7 weeks. The results suggest that that gestational VCZ exposure could not only increase miR132 and miR195a in penises and testes of the offspring, but also activate Hippo pathway and down-regulate Ar. These may directly inhibit cell proliferation, accelerate cell death by up-regulating the expression of some Ccns, and ultimately lead to penile and testicular damage and malformations in the offspring.

Keywords: Hippo; Vinclozolin; microRNA; penis; testis.

Background: The positioning of the stent at the flow-limiting segment is crucial for patients with extensive airway obstruction to relieve dyspnea. However, CT and flow-volume curves cannot detect the area of maximal obstruction.

Objectives: The aim of this study is to physiologically evaluate extensive airway obstruction during interventional bronchoscopy.

Methods: We prospectively measured point-by-point lateral airway pressure (Plat) at multiple points from the lower lobe bronchus to the upper trachea using a double-lumen catheter in 5 patients. The site of maximal obstruction was evaluated continuously to measure point-by-point Plat at multiple points when the airway catheter was withdrawn from the lower lobe bronchus to the upper trachea.

Results: Remarkable pressure differences occurred at the site of maximal obstruction assessed by point-by-point Plat measurements. After initial stenting in 1 case, migration of the maximal obstruction to a nonstented segment of the weakened airway was seen with extensive stenosis from the trachea to the bronchi. In the second case, in addition to radiological analysis, point-by-point Plat measurements could identify the location of the maximal obstruction which contributed to dyspnea.

Conclusions: Point-by-point Plat measurement could be used to detect the site of maximal obstruction physiologically. Furthermore, Plat measurement could assess the need for additional procedures in real time in patients with extensive airway obstruction.

Keywords: Flow limitation; Maximal obstruction; Migration; Pressure difference.

Marfan syndrome and related disorders. Marfan syndrome is an autosomal dominant disease, affecting about 1/5000 persons. It includes aortic wall fragility responsible for aortic root dilatation and risk of dissection, mitral valve prolapse, ophthalmological features (ectopia lentis, flat cornea, myopia), skeletal features (excessive height, arachnodactyly, thoracic deformity with pectus, scoliosis, and flat feet), cutaneous striae, particularly in the front of the shoulders, and dural ectasia. The gene affected is mainly FBN1 coding for fibrillin 1. Care includes beta-blockers, sport restriction, and prophylactic aortic surgery when the maximal aortic diameter (usually aortic root diameter) exceeds 50 mm. Many new related disorders have been discovered these last years.

Syndrome de marfan et syndromes apparentés. Le syndrome de Marfan est une maladie génétique dominante autosomique qui touche environ 1 personne sur 5 000. Elle se traduit par une fragilité de la paroi aortique (avec dilatation progressive et risque de dissection), un prolapsus valvulaire mitral, des signes ophtalmologiques (ectopie du cristallin, cornées plates, myopie forte), des signes squelettiques (grande taille, déformation thoracique avec pectus, scoliose, arachnodactylie, pieds plats), des signes cutanés (vergetures, surtout à l’avant des épaules) et une ectasie durale. Le gène en cause est généralement celui codant la fibrilline 1. Le traitement repose sur les bêtabloquants, la contre-indication aux sports violents, et la chirurgie aortique prophylactique lorsque le diamètre maximal de l’aorte (au niveau des sinus de Valsalva) dépasse 50 mm. De nombreux syndromes apparentés ont été découverts ces dernières années.

Keywords: Marfan Syndrome.

Introduction: Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood. Several medicinal plants possess curative and protective effect against thrombocytopenia associated with diseases or drugs.

Aim: In the present study, we have investigated the platelet augmentation activity of polyherbal formulation (VITA PLAT Capsule) in cyclophosphamide-induced thrombocytopenic rat model.

Materials and methods: Twenty-four albino Wistar rats were divided into four groups. Thrombocytopenia was induced in the rats by administering cyclophosphamide (25 mg/kg, i.p.) for three days to all the groups except normal controls. The test groups were given orally a polyherbal formulation suspended in normal saline for 14 days. Blood was withdrawn from the retro-orbital plexus of the rats on days 1, 7, and 14 of study to determine platelet counts in all groups. Clotting time and bleeding time were determined on the last day of study. Data were collected and analyzed using GraphPad Prism 8.

Results: The results showed that the polyherbal formulation treatment could significantly ameliorate platelet count in thrombocyto-penic rats in the initial as well as in the later phase. The total WBC count was also improved during later phase in test groups. However, there is no significant difference between clotting time and bleeding time in all groups.

Conclusions: Our study suggests a potential role of this formulation in the augmentation of platelet counts in various thrombocyto-penic disorders including a role in ameliorating the haemorrhagic complications of dengue fever.

Keywords: cyclophosphamide; platelet augmentation; polyherbal formulation; thrombocytopenia.

Lipoxygenase (LOX, EC 1.13.11.12) is a non-haeme iron-containing dioxygenase family that catalyzes the oxygenation of polyunsaturated fatty acids into bio-functionally fatty acid diverse (oxylipins) and plays vital role in plant growth and development and responses to abiotic and biotic stresses. Though LOX genes have been studied in many plant species, their roles in Brassicaceae species are still unknown. Here, a set of 14, 18, and 33 putative LOX genes were identified in Brassica rapa, Brassica oleracea and Brassica napus (allotetraploid rapeseed), respectively, which could be divided into 9-LOX (LOX1/5), 13-LOX type I (LOX3/4/6), and type II (LOX2) subgroups. There was an expansion of LOX2 orthologous genes in Brassicaceae. Most of the LOX genes are intron rich and conserved in gene structure, and the LOX proteins all have the conserved lipoxygenase and PLAT/LH2 domain. Ka/Ks ratio revealed that the majority of LOXs underwent purifying selection in Brassicaceae. The light-, ABA-, MeJA-related cis-elements and MYB-binding sites in the promoters of BnaLOXs were the most abundant. BnaLOXs displayed different spatiotemporal expression patterns and various abiotic/biotic stress responsive expression patterns. BnaLOX1/5 were slightly or no response to phytohormones and abiotic stresses. BnaLOX3/4/6 predominantly express in roots and were strongly up-regulated by salinity and PEG treatments, and BnaLOX3/4 were the methyl jasmonate (MeJA) and salicylic acid (SA) early response genes and strongly induced by infection of Sclerotinia sclerotiorum; while the BnaLOX2 members predominantly express in stamens, were MeJA and SA continuous response genes and strongly repressed by cold, heat and waterlogging treatments in leaves. Our results are useful for understanding the biological functions of the BnaLOX genes in allotetraploid rapeseed.

Keywords: Abiotic stress; JA; Lipoxygenase; Rapeseed; Sclerotinia sclerotiorum.

Background: Image registration is the process of aligning two or more images in a single coordinate. Now a days, medical image registration plays a significant role in computer assisted disease diagnosis, treatment, and surgery. The different modalities available in the medical image makes medical image registration as an essential step in Computer Assisted Diagnosis(CAD), Computer-Aided Therapy (CAT) and Computer-Assisted Surgery (CAS). Problem definition: Recently many learning based methods were employed for disease detection and classification but those methods were not suitable for real time due to delayed response and need of pre alignment,labeling.

Method: The proposed research constructed a deep learning model with Rigid transform and B-Spline transform for medical image registration for an automatic brain tumour finding. The proposed research consists of two steps. First steps uses Rigid transformation based Convolutional Neural Network and the second step uses B-Spline transform based Convolutional Neural Network. The model is trained and tested with 3624 MR (Magnetic Resonance) images to assess the performance. The researchers believe that MR images helps in success the treatment of brain tumour people.

Result: The result of the proposed method is compared with the Rigid Convolutional Neural Network (CNN), Rigid CNN + Thin-Plat Spline (TPS), Affine CNN, Voxel morph, ADMIR (Affine and Deformable Medical Image Registration) and ANT(Advanced Normalization Tools) using DICE score, average symmetric surface distance (ASD), and Hausdorff distance.

Conclusion: The RBCNN model will help the physician to automatically detect and classify the brain tumor quickly(18 Sec) and efficiently with out doing any pre-alignment and labeling.

Keywords: Advanced Normalization Tools; B-Spline transform; Brain Tumor Magnetic Resonance Images; Convolutional Neural Network; Deep learning; Medical image registrations; Rigid transformation.

Aim: To reveal the molecular mechanism of anti-angiogenic activity of semisynthetic triterpenoid CDDO-Im.

Materials and methods: Using re-analysis of cDNA microarray data of CDDO-Im-treated human vascular endothelial cells (HUVECs) (GSE71622), functional annotation of revealed differentially expressed genes (DEGs) and analysis of their co-expression, the key processes induced by CDDO-Im in HUVECs were identified. Venn diagram analysis was further performed to reveal the common DEGs, i.e. genes both susceptible to CDDO-Im and involved in the regulation of angiogenesis. A list of probable protein targets of CDDO-Im was prepared based on Connectivity Map/cheminformatics analysis and chemical proteomics data, among which the proteins that were most associated with the angiogenesis-related regulome were identified. Finally, identified targets were validated by molecular docking and text mining approaches.

Key findings: The effect of CDDO-Im in HUVECs can be divided into two main phases: the short early phase (0.5-3 h) with an acute FOXD1/CEBPA/JUNB-regulated pro-angiogenic response induced by xenobiotic stress, and the second anti-angiogenic step (6-24 h) with massive suppression of various angiogenesis-related processes, accompanied by the activation of cytoprotective mechanisms. Our analysis showed that the anti-angiogenic activity of CDDO-Im is mediated by its inhibition of the expression of PLAT, ETS1, A2M, SPAG9, RASGRP3, FBXO32, GCNT1 and HDGFRP3 and its direct interactions with EGFR, mTOR, NOS2, HSP90AA1, MDM2, SYK, IRF3, ATR and KIF14.

Significance: Our findings provide valuable insights into the understanding of the molecular mechanisms of the anti-angiogenic activity of cyano enone-bearing triterpenoids and revealed a range of novel promising therapeutic targets to control pathological neovascularization.

Keywords: Angiogenesis; CDDO-Im; CDDO-Me; Cyano enone; HUVECs; Molecular docking; Neovascularization; Network pharmacology.

Background: Gallbladder carcinoma (GBC), with early metastasis and high recurrence rates, is a enormous threat to health. As an anthraquinones monomer of traditional Chinese medicine Hedyotis diffusa, 2-hydroxy-3-methylanthraquinones (HMA) has been reported to inhibit the growth of several cancers. But in our preliminary study, HMA could only weakly induce GBC cell apoptosis.

Objective: To explore other possible mechanism underlying the inhibition effect of HMA on GBC, this proteomics analysis was performed.

Methods: A proteomics analysis was performed on one GBC cell line bought from the China Life Science Cell Bank. Several computational techniques were merged to develop analysis for those differently expressed proteins. A comparative protein-protein interaction network analysis was carried out among the differently expressed proteins to identify the proteins potentially inhibiting GBC. Thus, a GO and KEGG analysis was performed to identify the signaling pathways underlying a potential therapeutic role for HMA.

Results: A total of 285 proteins were affected by HMA, including 187 up-regulated and 98 down-regulated. The subcellular localization of differently expressed proteins were identified, including 142 in nuclear, 67 in cytoplasm, 67 in extracellular matrix, 46 in plasma membrane, 13 in mitochondrion, 3 in lysosome and 1 in cytoskeleton. HMA could regulate EGFR, FN1, PLG, PLAUR, LAMA3, HRG, THBS1, PLAT, KNG1, ENAM, SERPINE1, ECM1, interleukin-8 and trypsin in GBC. Most of the regulated proteins involve in cell migration. Pathways including PI3K-Akt, Wnt, HIF-1, focal adhesion, microRNAs were regulated by HMA.

Conclusion: HMA was shown to be an inhibition agent for GBC development, and this analysis would contribute to the development of new anti-GBC drugs.

Keywords: 2-hydroxy-3-methylanthraquinones; Hedyotis diffusa; gallbladder carcinoma; proteomics; traditional Chinese medicine.

The serine protease tissue plasminogen activator (tPA), encoded by the gene Plat, exerts a wide range of proteolysis-dependent and proteolysis-independent functions. In the developing brain, tPA is involved in neuronal development via the modulation of the proteolytic degradation of the extracellular matrix (ECM). Both lack of and excessive tPA are associated with neurodevelopmental disorders and with brain pathology. Astrocytes play a major role in neurite outgrowth of developing neurons as they are major producers of ECM proteins and ECM proteases. In this study we investigated the expression of Plat in developing and mature hippocampal and cortical astrocytes of Aldh1l1-EGFP-Rpl10a mice in vivo following Translating Ribosome Affinity Purification (TRAP) and the role of tPA in modulating astrocyte-mediated neurite outgrowth in an in vitro astrocyte-neuron co-culture system. We show that Plat is highly enriched in astrocytes in the developing, but not in the mature, hippocampus and cortex. Both the silencing of tPA expression in astrocytes and astrocyte exposure to recombinant tPA reduce neuritogenesis in co-cultured hippocampal neurons. These results suggest that astrocyte tPA is involved in modulating neuronal development and that tight control of astrocyte tPA expression is important for normal neuronal development, with both experimentally elevated and reduced levels of this proteolytic enzyme impairing neurite outgrowth. These results are consistent with the hypothesis that the ECM, by serving as adhesive substrate, enables neurite outgrowth, but that controlled proteolysis of the ECM is needed for growth cone advancement.

Keywords: Astrocytes; Brain Development; Neurite outgrowth; Pyramidal neurons; Tissue plasminogen activator; Translating Ribosome Affinity Purification.

Purpose: Tissue plasminogen activator (tPA) prevents steroid-induced reduction in aqueous humor outflow facility; however, its mechanism of action at the trabecular meshwork (TM) remains unclear. Enzymatic and non-enzymatic domains allow tPA to function as both an enzyme and a cytokine. This study sought to determine whether cytokine activity is sufficient to rescue steroid-induced outflow facility reduction.

Methods: Outflow facility was measured in C57BL/6J mice following triamcinolone acetonide exposure and either transfection of the TM using adenoviral vectors, encoding for enzymatically active and inactive tPA, or administration of the respective proteins. Protein injections were also administered to tPA deficient (PlatKO) and Mmp-9 deficient (Mmp-9KO) mice to determine the potential to rescue reductions in outflow facility and determine downstream mechanisms. Gene expression of matrix metalloproteinases (Mmp-2, -9, and -13) was measured in angle ring tissues containing the TM.

Results: Enzymatically active and inactive tPA (either produced after TM transfection or after direct administration) were equally effective in attenuating steroid-induced outflow facility reduction in C57BL/6J mice. They were also equally effective in rescuing outflow reduction in PlatKO mice and causing enhanced expression of matrix metalloproteinases. However, both enzymatically active and enzymatically inactive tPA did not improve outflow reduction in Mmp-9KO mice or increase the baseline outflow facility in naïve C57BL/6J mice.

Conclusions: tPA enzymatic activity is not necessary in the regulation of aqueous humor outflow. tPA can increase the expression of matrix metalloproteinases in a cytokine-mediated fashion. This cascade of events may eventually lead to extracellular matrix remodeling at the TM, which reverses outflow facility reduction caused by steroids.