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objective (s): Sexual dysfunctions are the most common problem in women during reproductive life and pregnancy is associated with physiological changes in sexual function.. This study aimed to evaluate the sexual quality of life of women during pregnancy. Methods: This cross-sectional study conducted on a sample of pregnant women referred to a teaching hospital affiliated to Qazvin University of Medical Sciences from October 2012 to July 2014. The data from these participants were obtained by a questionnaire consisting of three parts: demographic, history of obstetric information and sexual quality of life for women (SQOL-F). Women were followed-up during the 9-month in three trimester quarter. Data were analyzed by statistical tests (chi-square, t-test, and analysis of variance). Results: A total of 300 women participated in the study with an average age of 2 .29 ± 4.13 years. The results showed that as pregnancy progressed, sexual quality of life decreased significantly (P=0.03). Conclusion: The results showed that the sexual quality of life in pregnancy in the first, second and third trimesters varied and as pregnancy progressed sexual quality of life declined. Since sexual quality of life is an important issue in couple’s relationships, consultation for better adaptation to the physical and psychological changes during pregnancy seems essential.

In the commercial table egg industry, avian pathogenic E. coli (APEC) can lead to significant economic loss and bird mortality. The Poulvac E. coli vaccine (PECV) (Zoetis, Parsippany, NJ) may be administered to poultry post hatch via coarse spray or in drinking water to protect against APEC infections. The purpose of this experiment was to in ovo vaccinate commercial layers with various doses of the PECV to evaluate hatchability and post hatch development of the chicks through 21 d of age. Eggs were either non-injected or vaccinated at 18 d of incubation with a diluent-injected control or one of the PECV treatments which included a full dose (2.65 × 10 7 E. coli CFU/egg) or dilutions of the full dose to produce 2.65 × 10 5 , 2.65 × 10 3 , or 2.65 × 10 1 CFU/egg. Mean hatch of injected eggs was significantly (P < 0.0001) affected by treatment, with all the PECV treatments significantly decreasing hatch. Mean chick BW was determined on d of hatch and at 1, 2, and 3 wk post hatch, and mean chick length was determined at 3 wk post hatch. Chick BW was significantly (all P < 0.0001) different between treatments at 1, 2, and 3 wk of age, with the chicks that had received diluent alone having the highest BW, and the chicks that had received the full dose having the lowest BW. Chick length was significantly (P = 0.045) different between treatments, with the chicks in the full dose treatment having a shorter body length than the chicks in the 2 control groups. Cumulative mortality from 0 to 21 d of growout was 5.41% in the full dose treatment, whereas no mortalities were observed in the other treatment groups. While layer chicken embryos were able to survive to 3 wk post hatch after having received the PECV by in ovo injection, the full dose of the vaccine increased cumulative chick mortality and decreased chick BW through 3 wk post hatch., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katie Elliott reports equipment, drugs, or supplies was provided by Boehringer Ingelheim. Katie Elliott reports equipment, drugs, or supplies was provided by Zoetis Animal Health Co. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Effects of in ovo and dietary sources of calcidiol (25(OH)D 3 ), combined with Marek's disease vaccine (MDV), on the expression of genes involved with the antioxidant activity, muscle deposition, and immunity in the pectoralis major (P. major) muscle and spleen of 40 d of age (doa) broilers were investigated. The in ovo treatments were as follows: (1) non-injected; (2) the injection of 50 μL of commercial MDV, (3) MDV + 1.2, or (4) 2.4 μg of 25(OH)D 3 . All birds received either a commercial diet containing no supplemental 25(OH)D 3 (control) or the same diet supplemented with an additional 69 µg of 25(OH)D 3 per kg of feed (Hy-D diet). At 40 doa, the pectoralis major (P. major) muscle and spleen of 48 birds (six replicates per diet x in ovo treatment combination) were collected. When compared to un-supplemented commercial diet-fed birds, in birds that were fed the Hy-D diet, the expression of the TGF-β4 gene in the spleen and P. major muscle, and the GSH-P1 , GSH-P7 , SOD2 , MyoG , MyoD1 , and Pax3 genes in the P. major muscle were up-regulated, whereas the expression of the IL-1β , IL-8 , and CYP24A1 genes in the spleen and P. major muscle were down-regulated. Nevertheless, birds that received any of the in ovo injection doses of 25(OH)D 3 exhibited a higher expression of the IL-10 , TGF-β4 , and CYP27B1 genes in the spleen and P. major muscle. Furthermore, in comparison to the MDV-injected control group, the CAT , MyoD1 , and Pax3 genes in the P. major muscle were up-regulated, and the expression of the INF-γ , IL-1β and CYP24A1 genes in the spleen and the IL-8 , and IL-1β genes in the P. major muscle were down-regulated. In conclusion, a significant improvement in the expression of genes responsible for enzymatic antioxidant activity, protein synthesis, and inflammatory reactions in 40-day-old broilers occurred in response to in ovo and dietary supplemental 25(OH)D 3 , and supplemental 25OHD 3 provided via either route was used to enhance the expression of genes linked to vitamin D activity ( CYP27B1 , CYP24A1 ).

Introduction and Importance: Gastrointestinal bleeding is a serious health threat, especially when it originates from the small intestine, often termed small bowel bleeding (SBB). Hemangioendothelioma, a rare vascular tumor, can be a significant yet uncommon cause of gastrointestinal bleeding. This case report highlights hemangioendothelioma's diagnostic challenges and clinical significance in SBB., Case Presentation: A 16-year-old female experienced six months of intermittent massive rectorrhagia and melena, along with nausea, vomiting, loss of appetite, and abdominal pain. Initial endoscopic investigations, including colonoscopy and enteroscopy, did not identify the bleeding source. Imaging studies, including a CT scan and Meckel's scintigraphy, were also inconclusive. Persistent bleeding and a significant drop in hemoglobin levels led to exploratory laparotomy with intraoperative enteroscopy, which revealed a nodular lesion in the small intestine. Histopathological examination confirmed the lesion as hemangioendothelioma. Surgical resection of the lesion stopped the bleeding, and the patient recovered without complications, remaining asymptomatic during follow-ups at one and six months post-surgery., Clinical Discussion: Hemangioendothelioma is a rare, locally aggressive vascular tumor that can present with abdominal pain, bowel obstruction, anemia, and gastrointestinal bleeding. Due to its rarity and location, it often goes undetected in conventional endoscopy. The definitive diagnosis is made through histopathological examination, which shows characteristic endothelial cells and vascular structures. Surgical excision is the primary treatment, although there is a risk of recurrence and metastasis., Conclusion: This case underscores hemangioendothelioma's diagnostic challenges and clinical relevance in obscure gastrointestinal bleeding. Intraoperative enteroscopy plays a crucial role in the diagnosis and management. Clinicians should consider hemangioendothelioma in similar cases to ensure appropriate treatment and management., Competing Interests: Conflict of interest statement The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Influences the Marek's disease vaccine (MDV) alone or combined with the in ovo and dietary administration of 25-hydroxycholecalciferol (25OHD 3 ) on the expression of genes associated with the breast muscle deposition, adaptive and innate immunity, and antioxidant and vitamin D activities of 14 d-old broilers were investigated. Four in ovo treatments were: noninjected; commercial MDV-alone-injected (50 μl); or 50 μl of MDV containing 1.2 (MDV+25OHD 3 -1.2) or 2.4 (MDV+25OHD 3 -2.4) μg of 25OHD 3 . Two dietary treatments were a commercial diet containing 25OHD 3 (250 IU)/kg of feed (control) or the same diet supplemented with additional 25OHD 3 ( 2,760 IU)/kg of feed (Hy-D diet). One bird per pen (48 total) was sampled at 14 d for determination of the expression of genes involved with the muscle deposition (MyoD1, MyoG, Pax3, and Mrf4), immunity (INF-γ, IL-10, IL-8, IL-1β, and TGF-β4), antioxidant capacity (SOD1, SOD2, GSH-P1, GSH-P7, and CAT), and vitamin D activity (VDR, 1α-hydroxylase, and 24-hydroxylase) in the spleen and pectoralis major (P.major) muscle. The treatment differences were considered significant at P ≤ 0.05. In the P. major, Mrf4 and MyoG were up-regulated in Hy-D-fed birds. Also, the in ovo and dietary 25OHD 3 sources individually increased SOD2 gene expression in the P. major. In the spleen, the expressions of IL-1β and IL-8 were down-regulated and IL-10 and TGF-β4 gene expressions were up-regulated in Hy-D-fed birds than those commercial-fed broiler. In ovo and dietary 25OHD 3 sources enhanced vitamin D gene (1α-hydroxylase and 24-hydroxylase) activities in the breast and spleen. In ovo x dietary treatment interactions were significant for the MyoD1, IL-8, Pax3, TGF-β4 genes of the P. major, in which the combined MDV with 1.2 μg of 25OHD 3 enhanced their expressions in birds fed the Hy-D diet. In conclusion, both 25OHD 3 sources promoted the expression of genes associated with immunity and P. major growth. It is recommended that both 25OHD 3 sources can be used to promote the gene expression of 14-day-old broilers in the spleen and breast muscle when MDV administered in ovo., Competing Interests: DISCLOSURES There is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Investigations were performed to determine the systemic immune and small intestine (SI) morphological responses of Ross 708 broilers to the Marek's Disease vaccine (MDV) administered alone or in conjunction with the in ovo and dietary administration of calcifediol (25OHD 3 ). Live embryonated hatching eggs were assigned at random to 3 in ovo treatments at 18 d of incubation. Pre-specified in ovo treatments were: commercial MDV-alone-injected (50 µL) or commercial MDV containing 1.2 (MDV+25OHD 3 -1.2) or 2.4 (MDV+25OHD 3 -2.4) μg of 25OHD 3 . A noninjected control treatment was also included. For the growing phase, broilers received a commercial diet containing 250 IU of vitamin D 3 /kg (control) or a commercial diet supplemented with 2,760 IU of 25OHD 3 /kg (Hy-D diet). For determination of serum IgG, nitric oxide, and α-1-acid glycoprotein (AGP) at 14 and 40 d of age (doa), blood was collected from 1 bird per pen (48 total). In the duodenum, jejunum, and ileum of the same bird, villus length (VL), crypt depth (CD), VL to CD ratio (VCR), and villus surface area were also determined. There were no significant dietary x in ovo treatment interactions for any of the variables examined. However, birds fed Hy-D diets had lower serum AGP levels at 14 doa when compared to those fed un-supplemented commercial diets. Additionally, at 40 doa, birds in the MDV+25OHD 3 -1.2 and MDV+25OHD 3 -2.4 treatments experienced a decrease in serum AGP in comparison to those belonging to the noninjected and MDV-alone treatment groups. A higher jejunal VCR was observed at 14 and 40 doa in birds that belonged to the MDV+25OHD 3 -1.2 treatment when compared to those in the noninjected and MDV-alone treatment groups, and dietary Hy-D increased the VL of the duodenum and jejunum in birds at 14 and 40 doa when compared to those fed the commercial diet. In conclusion, both dietary or in ovo administration of 25OHD 3 lowered inflammatory reactions and improved the SI morphology of broilers that were in ovo-injected with the MDV., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The effects of the Marek's disease vaccine (MDV) on the live performance, breast meat yield, and incidence of woody breast myopathy (WBM) of Ross 708 broilers were investigated when administered alone or in conjunction with in ovo and dietary supplemental 25-hydroxycholecalciferol (25OHD 3 ). At 18 d of incubation (doi), four in ovo injection treatments were randomly assigned to live embryonated Ross 708 broiler hatching eggs: (1) non-injected; (2) commercial MDV alone; or MDV containing either (3) 1.2 or (4) 2.4 μg of 25OHD 3 . An Inovoject multi-egg injector was used to inject a 50 μL solution volume into each egg. The birds were provided a commercial diet that contained 250 IU of cholecalciferol/kg of feed (control) or a commercial diet that was supplemented with an additional 2760 IU of 25OHD 3 /kg of feed (HyD-diet). In the growout period, 14 male broilers were placed in each of 48 floor pens resulting 6 replicated pens per in ovo x dietary treatment combination. Live performance variable were measured at each dietary phases from 0 to 14, 15 to 28, and 29 to 40 d of age (doa). At 14 and 40 doa, pectoralis major (P. major) and pectoralis minor (P. minor) muscles were determined for one bird within each of the six replicate pens. At 41 doa, WBM incidence was determined. No significant main or interaction effects occurred for WBM among the dietary or in ovo injection treatments. However, in response to in ovo 25OHD 3 supplementation, BW and BWG in the 29 to 40 doa period and BWG and FCR in the 0 to 40 doa period improved. In addition, at 40 and 41 doa, breast meat yield increased in response to in ovo and dietary 25OHD 3 supplementation. Future research is needed to determine the possible reasons that may have been involved in the aforementioned improvements.

The combined effects of the in ovo injection of commercial Marek's disease vaccine (MDV) and various levels of 25-hydroxyvitamin D 3 (25OHD 3 ) on the hatch variables, immunological measurements, and gene expression of Ross 708 hatchling broilers were investigated. A total of 5 in ovo injection treatments that were applied at 18 d of incubation (doi) included: 1) noninjected (control); or a 50 μL solution volume of 2) MDV alone; or MDV combined with 3) 0.6 μg of 25OHD 3 ; 4) 1.2 μg of 25OHD 3 ; or 5) 2.4 μg of 25OHD 3 . At hatch, hatchability of set and live embryonated eggs, hatchling body weight, hatch residue analysis, serum IgY and alpha-1 acid glycoprotein (AGP) concentrations, and the expression of genes related to immunity (INFα, INFβ, INFγ, TLR-3, and TLR-21) and vitamin D 3 activity (1 α-hydroxylase, 24 hydroxylase, and vitamin D receptor) were determined. No significant treatment differences were observed for hatchability of set and live embryonated eggs, or for serum IgY and AGP concentrations. However, hatchling body weight was higher when MDV was combined with either 1.2 or 2.4 μg of 25OHD 3 than when MDV was provided alone or in combination with 0.6 μg of 25OHD 3 . Also, in comparison to the noninjected treatment group, the expression of the genes for 1 α-hydroxylase and 24 hydroxylase was improved when MDV was combined with either 1.2 or 2.4 μg of 25OHD 3 . Lastly, expression of the genes linked to viral detection (TLR-3) and antibody production (INF-β) was increased in those treatments that contained any level of 25OHD 3 . These results indicate that in comparison to controls, the effects of MDV were observed to be greater on hatchling BW and splenic gene expression when it was administered in combination with the 1.2 or 2.4 μg doses of 25OHD 3 . Further research is needed to determine the posthatch effects of the administration of various levels of 25OHD 3 in combination with MDV., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

It is well known that vitamin D plays a pivotal role in immune system modulation; however, its role in liver transplantation (LT) has not yet been well elucidated. This study aimed to assess the association between vitamin D status and LT outcomes. This retrospective cohort study was conducted on 335 registered cirrhotic patients with end-stage liver disease (ESLD) who underwent LT during 2019-2021 and had measurement of serum vitamin D before LT. The association of vitamin D levels before LT with the odds of acute cellular rejection (ACR) and risk mortality was assessed by applying logistic and cox regression, respectively. The mean MELD-Na and serum level of vitamin D were 20.39 ± 9.36 and 21.52 ± 15.28 ng/ml, respectively. In the final adjusted model, there was a significant association between vitamin D deficiency in the pre-transplant period and odds of ACR (odds ratio [OR] 2.69; 95% confidence interval [CI] 1.50-4.68). Although in the crude model, vitamin D deficiency in the pre-transplant period was significantly associated with an increased risk of mortality after two years of follow-up (Hazard ratio (HR) = 2.64, 95% CI 1.42-4.33), after adjustment for potential confounders, the association of vitamin D status and mortality became non-significant (HR = 1.46, 95% CI 0.71-3.00). The present study provides evidence that pre-transplant serum vitamin D levels may be a predictor for ACR in patients with cirrhosis undergoing LT., (© 2023. The Author(s).)

In the commercial egg industry, avian pathogenic Escherichia coli (APEC) can lead to significant economic loss. The Poulvac E. coli vaccine (PECV) is a commercially available attenuated live vaccine commonly applied via spray or drinking water to protect against losses associated with colibacillosis. The PECV has not been tested in layer hatching eggs using in ovo injection. Therefore, the purpose of this experiment was to determine the effects of injecting 50 μL of different doses of the PECV into Hy-Line W-36-layer hatching eggs on the hatchability and quality characteristics of hatchlings. At 18 d of incubation (DOI), treatments included 1 noninjected and 1 diluent-injected control. Furthermore, PECV treatments included a full dose (4.4 × 10 8 E. coli CFU) or serial dilutions of the full dose to produce 4.4 × 10 6 , 4.4 × 10 4 , or 4.4 × 10 2 CFU doses of E. coli. In ovo injections targeted the amnion. Percent hatchability of live embryonated eggs (HI), percent residue eggs, hatchling mortality, and female chick whole and yolk-free BW, relative yolk sac weight, and body length were among the variables examined. Treatment significantly (P < 0.0001) affected HI, with HI being highest in the control groups (97.3% in the noninjected and 94.2% in the diluent-injected), and with HI values being 89.0, 88.9, 84.4, and 71.2% in the 4.4 × 10 2 , 4.4 × 10 4 , 4.4 × 10 6 , and 4.4 × 10 8 CFU E. coli dose treatments, respectively. The percentage of live embryos that did not complete hatch but that pipped internally (P = 0.024) or externally (P < 0.0001) were significantly affected by treatment, with percentages being highest in the 4.4 × 10 8 CFU treatment. Female chick body length was significantly (P < 0.0001) affected by treatment and was longer in both control groups and in the 1 × 10 2 CFU E. coli treatment in comparison to all other treatments. Yolk-free female chick BW was significantly (P = 0.034) affected by treatment and was lower in the 4.4 × 10 6 CFU and 4.4 × 10 8 CFU treatments when compared to the diluent-injected control group. An increase in the E. coli concentration administered in the amnion of embryonated layer hatching eggs at 18 DOI decreased hatch success and female chick yolk-free BW and body length., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Currently, the escalation of microbial resistance poses a significant global challenge. Children are more susceptible to develop infections and therefore are prescribed antibiotics more frequently. The overuse and misuse of antibiotics in pediatric patients can play a considerable role in developing microbial resistance. Accordingly, many policies, including research into new antibiotic agents have been recommended to combat microbial resistance. Recent developments in novel antibiotics have shown promising results against multi-drug resistant (MDR) and extensive drug resistance (XDR) pathogens. However, as pediatric patients are typically excluded from the clinical trials of new medications, labeling and information about approved antibiotics should be improved. This study aimed to evaluate antibiotics having been introduced to the market in the last decade focusing on pediatric population. Methods: This study reviewed the published literatures on novel FDA-approved antibiotics released between 2010 and 2022. Results: Finally, seven newly approved antibiotics including ceftaroline fosamil, ceftazidime-avibactam, ceftolozane-tazobactam, ceftobiprole, imipenem-cilastatin-relebactam, meropenem-vaborbactam, and tedizolid were considered in the present review-article. All relevant data extracted from literatures, were discussed in different subtitles of "Pharmacology", "Mechanism of action", "Indication", "Dosage regimen and pharmacokinetic and pharmacodynamic properties", "Dosage adjustment in renal/liver failure", "Resistance pattern", and "Adverse drug events". Conclusion: This study reviewed available data on seven new antibiotic agents and their pharmacodynamic and pharmacokinetic properties, with a particular focus on their use in pediatric patients. The information presented in this review will be useful for healthcare professionals in selecting appropriate antibiotics for pediatric patients and for researchers in achieving the ideal therapeutic regimens.

The current commercial broiler embryo experiences a rapid metabolism and growth rate and may produce more heat than those of the past. Consequently, it may be beneficial to lower standard incubation temperature for commercial broiler hatching eggs. The purpose of this experiment was to determine if lowering incubation temperature at 12 d of incubation (DOI) would affect embryo temperature (ET) in embryonated Ross 708 broiler hatching eggs. From 0 to 12 DOI, eggs were incubated under standard conditions (37.50°C dry bulb, 29.76°C wet bulb). At 12 DOI, temperature transponders were aseptically placed on the inner air cell membrane to measure air cell temperature (ACT) as an estimate of ET in 120 eggs. The eggs were then randomly assigned to 4 separate still-air incubators, each containing 30 eggs. Two replicate incubators were maintained at a standard (STRT; 37.5°C) or low (LTRT; 35.6°C) temperature treatment between 12 and 21 DOI. A significant positive correlation existed between incubator air temperature (IAT) and ACT across temperature treatment and in the STRT. However, IAT was not significantly correlated with ACT in the LTRT. A significantly higher ACT was observed in the STRT than in the LTRT for 88% of the readings taken between 12 and 21 DOI. Percent egg weight loss (PEWL) between 13 and 17 DOI did not significantly differ between temperature treatments. From 13 to 17 DOI, there was a significant positive correlation between PEWL and ACT in the STRT, however, no significant correlation occurred between PEWL and ACT in the LTRT. Percent hatch of fertile eggs containing live embryos at 12 DOI was 93.3% in the STRT and 100% in the LTRT. However, time of hatch occurred 14 to 19 h later and hatchling BW was lower in the LTRT than in the STRT. Although lowering IAT at 12 DOI may improve hatchability, an associated delay in hatch and a decrease in hatchling BW may not be commercially acceptable., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In ovo administration as a possible alternative method of 6/85 MG vaccination was assessed. After 18 days of incubation (doi), the eggs were administered a particular dosage of a live attenuated 6/85 MG vaccine in either the air cell (AC) or amnion (AM). The treatments included non-injected eggs and eggs injected into the AC or AM with diluent alone as controls. Treatments also included eggs injected with diluent, which contained 1.73 × 10 2 , or 1.73 × 10 4 CFU of 6/85 MG. Hatchability of viable injected eggs (HI) and residual embryonic mortality were determined at 22 doi. At hatch and at three weeks posthatch, one hatched chick per treatment replicate was bled and swabbed for the detection of 6/85 MG in the choanal cleft using PCR, serum plate agglutination (SPA), and ELISA methods. The results show that AC in ovo injection of 6/85 MG had no negative impacts on HI or on the live performance of pullets, but that it failed to provide adequate protection ( p ≤ 0.0001) in hatchlings or three-week-old pullets. The 1.73 × 10 4 6/85 MG CFU dosage injected into the AM decreased the hatchability of injected eggs containing viable embryos (HI; p = 0.009) and was associated with a significant increase in late dead mortality ( p = 0.001). Hatchling and three-week-old chick mortalities ( p = 0.008) were significantly greater in the 1.73 × 10 4 CFU-AM treatment group in comparison with the other treatment groups. In addition, the 1.73 and 1.73 × 10 2 6/85 MG-AM treatments had no negative effects on the hatching process or on posthatch growth, and the 1.73 × 10 2 6/85 MG-AM treatment was more effective in the protection of pullets against MG ( p ≤ 0.0001) as compared with the low dosage and non-injected treatment groups. Further research is needed to examine the influence of the 6/85 MG in ovo vaccine on layer immune competence.

Effects of the in ovo injection of various levels of L-ascorbic acid (L-AA) on the performance and corneal erosion incidence in Ross 708 broilers exposed to 50 parts per million (ppm) of atmospheric ammonia (NH 3 ) after hatch were determined. A total of 1440 Ross 708 broiler embryos were randomly assigned to 4 treatments: non-injected (control), 0.85% sterile saline-injected (control), or saline containing 12 or 25 mg of L-AA. At hatch, 12 male chicks were randomly assigned to each of 48 battery cages with 12 replicate cages randomly assigned to each treatment group. All birds were exposed to 50 ppm of NH 3 for 35 d and the concentration of NH 3 in the battery cage house was recorded every 20 s. Mortality was determined daily, and mean body weight (BW), BW gain (BWG), average daily BW gain (ADG), and feed intake, as well as feed conversion ratio (FCR), were determined weekly. From 0 to 35 d of post-hatch age (doa), six birds from each cage were selected and sampled for eye erosion scoring. Incidences of corneal erosion were significantly higher at 21 and 28 doa in comparison to those at 14 and 35 doa, and at 21 doa, birds in the saline-injected group exhibited a higher incidence of corneal erosion compared to all other treatment groups. The in ovo injection of 12 mg of L-AA increased BWG ( p = 0.043) and ADG ( p = 0.041), and decreased FCR ( p = 0.043) from 0 to 28 doa in comparison to saline-injected controls. In conclusion the in ovo administration of 12 mg of L-AA may have the potential to improve the live performance of broilers chronically exposed to high aerial NH 3 concentrations, but further study is needed to determine the physiological and immunological factors that may contribute to this improvement.

Effects of the dietary and in ovo administration of L-ascorbic acid (L-AA) on the performance, plasma nitric oxide, and eye L-AA concentrations of Ross 708 broilers were investigated. At 17 days of incubation, live embryonated hatching eggs were randomly assigned to a non-injected or sham-injected (100 μL of saline) control group, or a group injected with either 12 or 25 mg of L-AA suspended in 100 μL of saline. Chicks received a commercial diet with or without 200 mg/kg of supplemental L-AA and were randomly assigned to each of 6 replicate floor pens in each in ovo injection-dietary treatment combination. Weekly live performance variables through 14 days of post hatch age (doa) and the eye weights in both sexes at 0, 7, and 14 doa were determined. At 0 and 14 doa, plasma nitric oxide levels and eye L-AA concentrations of one bird of each sex in each pen were determined. Dietary supplemental L-AA decreased feed intake and growth between 0 and 7 doa, but from 8 to 14 doa; all birds fed supplemental L-AA had a lower feed conversion ratio. At 14 doa, male chicks had higher eye L-AA concentrations and lower plasma nitric oxide levels when treated in ovo with 12 mg of L-AA. In conclusion, dietary L-AA may be used to improve feed conversion in the second week of broiler post hatch growth. However, the in ovo administration of 12 mg of L-AA can increase male eye L-AA concentrations and is effective in reducing their general inflammatory response.

Effects of the in ovo administration of two vitamin D 3 sources (vitamin D 3 (D 3 ) and 25-hydroxyvitamin D 3 (25OHD 3 )) on the expression of D 3 activity- and immunity-related genes in broilers subjected to a coccidiosis infection were investigated. At 18 d of incubation (doi), five in ovo injection treatments were administrated to live embryonated Ross 708 broiler hatching eggs: non-injected (1) and diluent-injected (2) controls, or diluent injection containing 2.4 μg of D 3 (3) or 2.4 μg of 25OHD 3 (4), or their combination (5). Birds in the in ovo-injected treatments were challenged at 14 d of age (doa) with a 20× dosage of a live coccidial vaccine. At 14 and 28 doa, the expression of eight immunity-related genes (IL-2, IL-6, IL-10, TLR-4, TLR-15, MyD88, TGF-β4, and IFN-γ) and four D 3 activity-related genes (1α-hydroxylase, 25-hydroxylase, 24-hydroxylase, and VDR ) in the jejunum of one bird in each treatment-replicate group were evaluated. No significant treatment effects were observed for any of the genes before challenge. However, at 2 weeks post-challenge, the expression of 1α-hydroxylase, TGF-β4, and IL-10 increased in birds that received 25OHD 3 alone in comparison to all the other in ovo-injected treatment groups. Additionally, the expression of 24-hydroxylase and IL-6 decreased in birds that received 25OHD 3 in comparison to those injected with diluent or D 3 alone. It was concluded that the in ovo injection of 2.4 μg of 25OHD 3 may improve the intestinal immunity as well as the activity of D 3 in Ross 708 broilers subjected to a coccidiosis challenge.

Biallelic pathogenic variants in the nuclear gene DARS2 (MIM# 610956), encoding the mitochondrial enzyme aspartyl-tRNA synthetase (MT-ASPRS) cause leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) (MIM# 611105), a neurometabolic disorder characterized by progressive ataxia, spasticity, developmental arrest or regression and characteristic brain MRI findings. Most patients exhibit a slowly progressive disease course with motor deterirartion that begins in childhood or adolescence, but can also occasionaly occur in adulthood. More severe LBSL presentations with atypical brain MRI findings have been recently described. Baker's yeast orthologue of DARS2, MSD1, is required for growth on oxidative carbon sources. A yeast with MSD1 knockout (msd1Δ) demonstrated a complete lack of oxidative growth which could be rescued by wild-type MSD1 but not MSD1 with pathogenic variants. Here we reported two siblings who exhibited developmental regression and ataxia with different age of onset and phenotypic severity. Exome sequencing revealed 2 compound heterozygous missense variants in DARS2: c.473A>T (p.Glu158Val) and c.829G>A (p.Glu277Lys); this variant combination has not been previously reported. The msd1Δ yeast transformed with plasmids expressing p.Glu259Lys, equivalent to human p.Glu277Lys, showed complete loss of oxidative growth and oxygen consumption, while the strain carrying p.Gln137Val, equivalent to human p.Glu158Val, showed a significant reduction of oxidative growth, but a residual ability to grow was retained. Structural analysis indicated that p.Glu158Val may interfere with protein binding of tRNA Asp , while p.Glu277Lys may impact both homodimerization and catalysis of MT-ASPRS. Our data illustrate the utility of yeast model and in silico analysis to determine pathogenicity of DARS2 variants, expand the genotypic spectrum and suggest intrafamilial variability in LBSL., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The transmission of the ts-11 strain of Mycoplasma gallisepticum (MG) vaccine (ts-11MGV) between incubated eggs and between hatchlings that was administrated via in ovo injection, and its subsequent effects on their posthatch performance were evaluated. Marek's disease diluent alone (sham-injected) or containing either 3.63 × 10 1 , 10 2 , 10 3 , or 10 4 cfu of ts-11MGV was manually in ovo-injected into the amnion on 18 days of incubation. Egg residue analysis, percentage incubational egg weight loss, hatchability of viable injected eggs, and hatchling body weight (BW) were assessed. Selected hatchlings from each treatment replicate group were swabbed in the choanal cleft for MG DNA detection. Female chick live performance was also assessed through 21 days of posthatch age. Unexposed control sentinel chicks were allocated to each treatment replicate group to assess horizontal transmission. Birds were later swabbed and bled respectively, for detection of MG DNA and IgM production at 21 days posthatch. In all birds, no MG DNA was detected and SPA tests for IgM were negative. Among all variables, only 0 to 21 day BW gain was significantly affected by treatment and was lower in the 3.63 × 10 4 ts-11 MGV treatment in comparison to all the other treatments. Because ts-11MGV does not exhibit vertical or horizontal transmission capabilities under commercial conditions, it may not be a good candidate for in ovo injection.

Effects of the in ovo injection of various concentrations of L-ascorbic acid (L-AA) on the hatchability and retention levels of L-AA in the serum of broiler embryos were investigated. A total of 960 Ross 708 broilers hatching eggs were randomly divided into four treatment groups: non-injected control, saline-injected control, and saline containing either 12 or 25 mg of L-AA. At 18 days of incubation (doi), injected eggs received a 100 μL volume of sterile saline (0.85%) alone or containing one of the two L-AA levels. Percentage egg weight loss was also determined from 0 to 12 and 12 to 18 doi. Hatch residue analysis was conducted after candling to determine the staging of embryo mortality. At approximately 21 doi, hatchability of live embryonated eggs (HI) and hatchling body weight (BW) were determined. Blood samples were taken at 6 and 24 h after L-AA in ovo injection to determine serum L-AA concentrations. Serum L-AA concentrations, HI, and hatchling BW did not differ among all treatment groups. However, chicks in the non-injected group had a higher ( p = 0.05) embryonic mortality at hatch in comparison to those in the 12 mg of L-AA in saline and saline alone treatment groups. These results suggest that the in ovo injection of high levels of L-AA (12 and 25 mg) does not negatively affect HI or serum concentrations of L-AA but has the potential to promote embryonic livability. Further research is needed to determine the retention time of L-AA in the other tissues of broilers, including the cornea of the eye, in response to different levels of supplemental L-AA.

In broilers challenged with coccidiosis, effects of in ovo vitamin D 3 (D 3 ) and 25-hydroxyvitamin D 3 (25OHD 3 ) administration on their inflammatory response and small intestine morphology were evaluated. At 18 d of incubation (doi), a 50 μL volume of the following 5 in ovo injection treatments was administrated: non-injected (1) and diluent injected (2) controls, or diluent injection containing 2.4 μg D 3 (3) or 2.4 μg 25OHD 3 (4), or their combination (5). Four male broilers were randomly allocated to each of eight isolated replicate wire-floored battery cages at hatch, and birds were challenged at 14 d of age (doa) with a 20x live coccidial vaccine dosage. One bird from each treatment-replicate (40 birds in each of 8 replicates per treatment) was bled at 14 and 28 doa in order to collect blood for the determination of plasma IL-1β and nitric oxide (NO) concentrations. The duodenum, jejunum, and ilium from those same birds were excised for measurement of villus length, crypt depth, villus length to crypt depth ratio (VCR), and villus surface area. In ovo injection of 2.4 μg of 25OHD 3 resulted in a reduction in plasma NO levels as compared to all other treatments at 28 doa. Additionally, duodenal VCR increased in response to the in ovo injection of 25OHD 3 when compared to the diluent, D 3 alone, and the D 3 + 25OHD 3 combination treatments at two weeks post-challenge (28 doa). Therefore, it can be concluded that 2.4 μg of 25OHD 3 , when administrated in ovo at 18 doi, may be used to decrease the inflammatory reaction as well as to enhance the small intestine morphology of broilers during a coccidiosis challenge.

Vanishing white matter (VWM) is a leukodystrophy caused by recessive variants in the genes EIF2B1-EIF2B5 . It is characterized by chronic neurologic deterioration with superimposed stress-provoked episodes of rapid decline. Disease onset spans from the antenatal period through senescence. Age at onset predicts disease evolution for patients with early onset, whereas disease evolution is unpredictable for later onset; patients with infantile and early childhood onset consistently have severe disease with rapid neurologic decline and often early death, whereas patients with later onset have highly variable disease. VWM is rare, but likely underdiagnosed, particularly in adults. Apart from measures to prevent stressors that could provoke acute deteriorations, only symptomatic care is currently offered. With increased insight into VWM disease mechanisms, opportunities for treatment have emerged. EIF2B1-EIF2B5 encode the 5-subunit eukaryotic initiation factor 2B complex, which is essential for translation of mRNAs into proteins and is a principal regulator of the integrated stress response (ISR). ISR deregulation is central to VWM pathology. Targeting components of the ISR has proven beneficial in mutant VWM mouse models, and several drugs are now in clinical development. However, clinical trials in VWM pose considerable challenges: low numbers of known patients with VWM, unpredictable disease course for patients with onset after early childhood, absence of intermediate biomarkers, and novel first-in-human molecular targets. Given these challenges and considering the critical need to offer therapies, we have formulated recommendations for enhanced diagnosis, drug trial setup, and patient selection, based on our expert evaluation of molecular, laboratory, and clinical data., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Cervical cancer, the fourth most frequent women cancer worldwide, is mostly (about 99%) associated with human papillomavirus (HPV). Despite availability of three effective prophylactic vaccines for more than one decade and some other preventive measures, it is still the fourth cause of cancer death among women globally. Thus, development of therapeutic vaccines seems essential, which has been vastly studied using different vaccine platforms. Even with very wide efforts during the past years, no therapeutic vaccine has been approved yet, which might be partly due to the complex events and interactions taken place in the tumor microenvironment. On the other hand, immunotherapy has opened its way into the management plans of some cancers. The recent approval of pembrolizumab for the treatment of metastatic/recurrent cervical cancer brings new hopes to the management of this disease, while some other immunotherapeutic approaches are also under investigation either alone or in combination with vaccines. Here, following a summary about HPV and its pathogenesis, cervical cancer therapeutic vaccines would be reviewed. Cell-based vaccines as well as immunomodulation and other modalities used along with vaccines would be also discussed., Competing Interests: Conflicts of interest No conflict of interests is declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Effects of the in ovo administration of vitamin D 3 (D 3 ) and 25-hydroxyvitamin D 3 (25OHD 3 ) on broiler intestinal lesion incidence, performance and breast meat yield after a coccidiosis challenge were investigated. On each of 10 incubator tray levels, 10 Ross 708 broiler hatching eggs were randomly assigned to each of the following 5 in ovo injection treatments administrated at 18 d of incubation (doi): 1) noninjected; 2) diluent; diluent containing either 3) 2.4 μg D 3 (D 3 ), 4) 2.4 μg 25OHD 3 (25OHD 3 ), or 5) 2.4 μg D 3  + 2.4 μg 25OHD 3 (D 3 +25OHD 3 ). A 50 μL solution volume was injected into each egg using an Inovoject multi-egg injector. Four male chicks were randomly assigned to each of 80 battery cages in each of 2 rooms. Half of the treatment-replicate cages (8) in each room were challenged with a 20× live coccidial vaccine at 14 d of age (doa). One randomly selected bird from each of 4 treatment-replicate cages was scored for coccidiosis lesions before and 2 wk after challenge. Mean BW, BW gain (BWG), feed intake, and feed conversion ratio were determined for all birds from 0 to 14, 15 to 28, and 29 to 41 doa. Carcass weight, and the absolute and relative (% of carcass weight) weights of carcass parts were determined in 3 birds per treatment-replicate cage at 42 doa. Hatchability of live embryonated injected eggs and hatch residue were not affected by treatment. Across challenge treatment, birds in the 25OHD 3 treatment group experienced an increase in BWG between 29 and 41 doa when compared to the D 3 or diluent-injected birds. Furthermore, pectoralis major muscle percentage tended (P = 0.059) to increase in birds belonging to the 25OHD 3 treatment in comparison to birds in the D 3 or diluent-injected treatments. These results indicate that regardless of challenge treatment, 2.4 μg of 25OHD 3 may increase the BWG and breast meat yield of birds relative to those that only received an injection of commercial diluent., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Effects of the in ovo-injection of vitamin D 3 (D 3 ) and 25-hydroxyvitamin D 3 (25OHD 3 ) on broiler performance, carcass characteristics, and woody breast myopathy (WBM) incidence were investigated. Live embryonated Ross 708 broiler hatching eggs (2,880) were randomly assigned to one of the following in ovo injection treatments: (1) diluent (50 μL); diluent (50 μL) containing either (2) 2.4 μg D 3 ; (3) 2.4 μg 25OHD 3 ; or (4) 2.4 μg D 3  + 2.4 μg 25OHD 3 . Eggs were injected at 18 d of incubation (doi) using an Inovoject multiegg injector. At hatch, 18 male chicks were randomly placed in each of 6 replicate pens belonging to each in ovo injection and, dietary treatment combination. Birds were fed either a commercial diet or a diet restricted in calcium and phosphorous (ReCaP) content by 20% for the starter, grower and finisher dietary phases. Broiler performance was determined in each dietary phase and breast muscle yield was also determined at 14 and 40 d of age (doa). At 41 and 46 doa, birds were processed for determination of WBM, carcass weight, and the absolute and relative (% of carcass weight) weights of various carcass parts. Compared to birds fed the commercial diet, birds fed ReCaP diets experienced a reduction in performance from 14 to 40 doa, in breast meat yield at 41 and 46 doa, and in WBM at 41 and 46 doa. At 14 and 40 doa, breast meat yield in birds that received an in ovo injection of 25OHD 3 alone was higher compared to birds that received diluent alone or a combination of D 3 and 25OHD 3 . Lower WBM incidence in ReCaP-fed birds was associated with a lower breast weight. An increase in breast meat yield in response to 25OHD 3 alone may be due to improved immunity and small intestine morphology. However, further study is needed to determine the aforementioned effects., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Effects of the in ovo injection of vitamin D 3 (D 3 ) and 25-hydroxyvitamin D 3 (25OHD 3 ) on the immunity and small intestine morphology of broilers fed calcium and phosphorus-restricted diets were investigated. At 18 d of incubation (doi), live embryonated Ross 708 broiler hatching eggs were in ovo-injected with a 50 μL solution of one of the following treatments using an Inovoject multiegg injector: 1) diluent (control); diluent containing either 2) 2.4 μg D 3 ; 3) 2.4 μg 25OHD 3 ; or 4) 2.4 μg D 3  + 2.4 μg 25OHD 3 . At hatch, 18 randomly selected male broilers belonging to one of the 4 in ovo injection treatments were placed in each of 12 floor pens and were fed either a commercial diet or a diet restricted by 20% in calcium and available phosphorus (ReCaP) content for the starter, grower and finisher dietary phases. Concentrations of plasma IgG and IgM at 14 d of age (doa) and α-1-acid glycoprotein at 40 doa were determined. Bursa, liver, spleen, duodenum, jejunum, and ileum weights were recorded at 7, 14, and 40 doa and small intestine histology was evaluated at 14 and 40 doa. Blood and organ samples were randomly collected from 1 bird in each of the 6 replicate pens within each of the 8 (4 in ovo x 2 dietary) treatment groups. Plasma IgG levels were higher in 25OHD 3 than in diluent or D 3 in ovo-injected birds. At 14 doa, a higher jejunal villus length (VL) to crypt depth (CD) ratio (RVC) was observed in birds that were in ovo-injected with 25OHD 3 alone as compared to all other in ovo injection treatments. At 40 doa, ileal VL increased and jejunal CD decreased in commercial diet-fed birds compared to ReCaP diet-fed birds. In conclusion, the in ovo injection of 25OHD 3 alone increased the immune response and improved the small intestine morphology and subsequent nutrient uptake of Ross 708 broilers. However, a ReCaP diet was observed to be detrimental to their small intestine morphology., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Based on some previous observational studies, there is a theory that suggests a potential relationship between Helicobacter pylori (H. pylori) colonization and celiac disease (CeD); however, the type of this relationship is still controversial. Therefore, we aimed to conduct a systematic review and meta-analysis to explore all related primary studies to find any possible association between CeD and human H. pylori colonization., Data Sources: Studies were systematically searched and collected from four databases and different types of gray literature to cover all available evidence. After screening, the quality and risk of bias assessment of the selected articles were evaluated., Synthesis Methods: Meta-analysis calculated pooled odds ratio (OR) on the extracted data. Furthermore, heterogeneity, sensitivity, subgroups, and publication bias analyses were assessed., Results: Twenty-six studies were included in this systematic review, with a total of 6001 cases and 135512 control people. The results of meta-analysis on 26 studies showed a significant and negative association between H. pylori colonization and CeD (pooled OR = 0.56; 95% CI = 0.45-0.70; P < 0.001), with no publication bias (P = 0.825). The L'Abbé plots also showed a trend of having more H. pylori colonization in the control group. Among subgroups, ORs were notably different only when the data were stratified by continents or risk of bias; however, subgroup analysis could not determine the source of heterogeneity., Conclusions: According to the meta-analysis, this negative association might imply a mild protective role of H. pylori against celiac disease. Although this negative association is not strong, it is statistically significant and should be further considered. Further investigations in both molecular and clinic fields with proper methodology and more detailed information are needed to discover more evidence and underlying mechanisms to clear the interactive aspects of H. pylori colonization in CeD patients., Systematic Review Registration Number (prospero): CRD42020167730 https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=167730., Competing Interests: The authors have declared that no competing interests exist.

The effects of the in ovo administration of vitamin D 3 (D 3 ) and its metabolite, 25-hydroxyvitamin D 3 (25OHD 3 ) , on the performance, breast meat yield, and inflammatory responses of broilers fed commercial diets were investigated. Live embryonated Ross 708 broiler hatching eggs were randomly assigned to one of the following 5 in ovo injection treatments at 18 d of incubation: 1) noninjected; 2) diluent; diluent containing 3) 2.4-μg D 3 , 4) 2.4-μg 25OHD 3 , or 5) 2.4-μg D 3  + 2.4-μg 25OHD 3 . A 50-μL solution volume of each prespecified treatment was injected into each egg using an Inovoject multiegg injector. At hatch, 18 male chicks were randomly assigned to each of 30 floor pens. The BW, BW gain, feed intake, and feed conversion ratio of the birds were determined in each dietary phase. At 14, 28, and 39 d of posthatch age (doa), plasma α-1-acid glycoprotein (AGP) levels in 1 bird in each of 6 replicate pens per treatment were determined at 14 and 39 doa. The pectoralis major and minor weights of those same birds were also determined. The remaining birds were processed at 43 doa, and the weights of their processing parts were determined. At 39 doa, the in ovo injection of 25OHD 3 alone decreased plasma AGP concentrations in comparison with the noninjected, diluent, and D 3 -alone treatment groups. In addition, birds that received 25OHD 3 alone had a greater BW at 42 doa than birds in the noninjected, diluent, and D 3 -alone treatment groups. At 39 and 43 doa, breast meat yield was increased in response to the in ovo injection of 25OHD 3 alone in comparison to all other treatments. These results indicate that the in ovo injection of 2.4 μg of 25OHD 3 resulted in an improvement in the performance and inflammatory responses of broilers. A reduction in the inflammatory response subsequent to the in ovo injection of 2.4 μg of 25OHD 3 may have led to an increase in broiler performance., (Copyright © 2020. Published by Elsevier Inc.)

Effects of the in ovo injection of vitamin D 3 (D 3 ) and 25-hydroxycholecalciferol (25OHD 3 ) on broiler embryo serum 25OHD 3 concentrations, hatchability, and hatchling somatic characteristics were determined. Eggs from a 35-wk-old commercial Ross 708 broiler breeder flock were set in a single-stage incubator with 11 treatments represented on each of 8 incubator tray levels (blocks). Each treatment group within a flat on each tray level contained 30 eggs. Control treatments were noninjected and diluent injected. Vitamin treatments were commercial diluent containing 0.6 μg D 3 , 0.6 μg 25OHD 3 , 0.6 μg D 3 + 0.6 μg 25OHD 3 , 1.2 μg D 3 , 1.2 μg 25OHD 3 , 1.2 μg D 3 + 1.2 μg 25OHD 3 , 2.4 μg D 3 , 2.4 μg 25OHD 3 , or 2.4 μg D 3 + 2.4 μg 25OHD 3 . At 432 h of incubation (hoi), 50-μL solution volumes were injected. Blood samples were collected at 462 hoi for serum 25OHD 3 analysis, and hatchability of injected live embryonated eggs (HI) was determined at 492 and 516 hoi. At 516 hoi, hatchling yolk-free BW and weights of the liver and yolk sac were determined. Percentage of yolk moisture and dry mater was calculated. At 492 and 516 hoi, HI did not differ between treatments. Embryos that received 1.2 μg or more of either vitamin D 3 source alone or in combination had higher serum 25OHD 3 concentrations than those that were injected with diluent alone or diluent containing 0.6 μg of D 3 . Hatchlings that received 1.2 or 2.4 μg of 25OHD 3 had higher percentage of yolk dry matter or lower percentage of yolk moisture levels than noninjected controls and those that received D 3 alone at any level. These results indicate that the in ovo injection of either vitamin D 3 source at levels equal to or higher than 1.2 μg resulted in serum 25OHD 3 concentrations that were higher than that of noninjected controls. In addition, the in ovo injection of 1.2 μg or higher of either vitamin D 3 source did not negatively affect broiler HI or chick quality., (Copyright © 2020. Published by Elsevier Inc.)

Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration., Competing Interests: Declaration of Interests C.A.W. serves on advisory boards for the Allen Brain Institute, Third Rock Ventures, and Maze Therapeutics and on editorial boards for Annals of Neurology, Trends in Neurosciences, and neuroDEVELOPMENTS. M.S. received research funding from Roche, Novartis, Pfizer, LAM Therapeutics, and Quadrant Biosciences; has served on the scientific advisory boards of Sage Therapeutics, Roche, Takeda, Celgene, and the PTEN Research Foundation; and serves on the Board of the Tuberous Sclerosis Alliance. All of these activities are outside of the submitted manuscript. J.S.C. is a consultant for Invitae. D.V. serves as a consultant to SK Life Science and Otsuka Pharmaceuticals, is on the speaker’s bureaus for UCB and Greenwich Pharmaceuticals, and conducts industry-supported clinical drug trials for SK Life Science, Biogen, and UCB Pharmaceuticals. K.M. is an employee of GeneDX, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The effects of in ovo injected vitamin D 3 source on eggshell temperature (ET) and performance of broilers through 14 D of age (doa) were investigated. Eggs from a 35-wk-old commercial Ross 708 broiler breeder flock were set in a single-stage incubator with 4 treatments representing each of 12 incubator tray levels (blocks). At 432 h of incubation (hoi), noninjected and diluent-injected (50 μL) groups were control treatment groups. Vitamin treatments in the commercial diluent were as follows: 2.4 μg of vitamin D 3 (D 3 ) or 25-hydroxylcholecalciferol (25OHD 3 ). After injection, ET readings were recorded (435, 441, 453, 459, and 465 hoi) by infrared thermometry. Hatchability, hatchling BW, and percentage of male and female hatchlings were determined at 502 hoi. Equal numbers of male and female chicks were placed in each pen and grown out for 14 doa. On a per-pen basis, BW was recorded after hatching at day 7 and 14 doa, and BW gain, average daily BW gain, feed intake (FI), and feed conversion ratio (FCR) were calculated between 0 to 14 doa. The ET of eggs significantly fluctuated during the postinjection time period; however, the type of vitamin D 3  source injected did not affect ET. Nevertheless, the injection of 25OHD 3 resulted in a lower late embryo mortality than the diluent and D 3 injection treatments. In addition, birds that received 25OHD 3 had a lower FI and FCR than birds in all other treatments. In conclusion, the in ovo injection of 25OHD 3 has the potential to improve early posthatch broiler performance without affecting ET., (Copyright © 2019. Published by Elsevier Inc.)

The current study was designed to investigate the effects of the in ovo injection of different dosages of L-ascorbic acid (AA) on posthatch growth performance, carcass characteristics, plasma antioxidant capacity, and meat quality in broiler chickens. A total of 2,220 Ross 708 broiler hatching eggs containing live embryos at 17 D of incubation were subjected to 1 of 6 treatments (trt): non-injected control, saline-injected control, or saline containing 3, 6, 12 or 36 mg of AA. An Inovoject m semi-automatic multi-egg injector was used to inject a 100 μL volume of sterile saline (0.85%) alone or containing the different AA dosage into each egg. After hatch, 14 male hatchlings from each trt group were randomly selected and placed in each of 10 replicate floor pens for growth performance evaluation through 45 D posthatch. Chicks from the 3 and 6 mg AA trt groups had a higher average daily BW gain and a higher feed intake compared to the saline-injected control group during the grower phase. Chicks in the 12 mg AA trt group exhibited a better feed efficiency in the late finisher phase and the entire growing phase than those in the saline-injected control group. Higher thigh and leg percentages were observed in chicks from the 3 and 6 mg AA trt groups than in the non-injected control group. Compared to the non-injected or saline-injected control groups, birds in the 12 mg AA trt group were observed to have a lower plasma malondialdehyde content during the grower and finisher phases, and breast muscle tenderness was elevated in chicks from the 36 mg AA trt group. Taken together, these results suggest that the in ovo injection of AA (3 to 12 mg per egg) have lasting positive effects on the posthatch growth, leg muscle development, and systemic antioxidant capacity of broilers. Higher injected dosages of AA (36 mg per egg) may also have the potential to improve broiler meat quality., (© 2019 Poultry Science Association Inc.)

The current study was conducted to determine the possible effects of the in ovo administration of different dosages of L-ascorbic acid (AA) to broiler hatching eggs on hatchability and its potential for reducing the adverse effects of delayed placement.A total of 702 broiler hatching eggs was hand-injected at 17 d of incubation (DOI) with 100 μL of sterile saline (0.85%) alone or containing 0.5, 1.5, 4.5, or 13.5 mg AA. Hatchability was recorded every 5 h from 480 h to 505 hours. Results showed that AA injection did not affect embryo BW as percentage of set egg weight or yolk sac weight as percentage of embryo weight at 19.5 DOI. The hatching time of all embryos that received an AA in ovo injection was between 480 and 495 h of incubation, and significantly fewer embryos hatched before 480 h in comparison to non-injected controls. Hatchability (above 92% in all groups) was not significantly affected by injection treatment. However, fertile eggs injected with saline containing 4.5 mg AA had the highest hatchability. At 21 DOI, hatching BW as a percentage of set egg weight and yolk sac weight as a percentage of BW were numerically higher in AA injection groups. An in ovo injection of AA at a 13.5 mg/egg level resulted in a numerically higher BW as a percentage of set egg weight. The in ovo injection of AA did not reduce the adverse effects of a 48-hour posthatch pre-placement holding time on BW or on yolk sac absorption. Overall, in ovo injection of L-ascorbic acid (0.5 to 13.5 mg/egg) into fertile broiler hatching eggs at 17 DOI did not negatively affect hatchability or embryo development, and did not prevent the negative effects of a 48-hour posthatch holding time on BW and yolk sac absorption. The range of tolerance as well as the optimal dosage of in ovo-injected AA warrants future study.

Background. Many types of toothpastes contain substances that can remineralize initial enamel caries. This study aimed to assess the effect of nano-hydroxyapatite (NHA) on microhardness of artificially created carious lesions. Methods. In this in vitro study, NHA was prepared using sol-gel technique and added to the toothpaste with 7% concentration. A total of 80 extracted sound teeth were collected. The crowns were polished using 500-grit abrasive paper. The specimens were randomly coded from 1 to 80. Number 1 to 40 were assigned to group A and numbers 41 to 80 to group B. The microhardness was measured using HVS-1000 Vickers microhardness tester. The specimens were demineralized using 37% phosphoric acid for 3 minutes in order to create artificial carious lesions and then were rinsed with water, air-sprayed for 3 minutes and dried. Microhardness was measured again. Next, the specimens were brushed for 15 days, twice daily, for 15 seconds. After 15 days, microhardness was measured again. Toothpaste A contained NHA and fluoride and toothpaste B contained fluoride alone. Data were analyzed using SPSS 16, with one-sample Kolmogorov-Smirnov test and ANOVA at a significance level of P<0.05. Results. The microhardness of specimens significantly decreased following acid exposure (P<0.01) but increased again in both groups after exposure to toothpastes. The increase in microhardness was significantly greater in group A (P<0.01). Conclusion. The toothpaste containing NHA was more effective than the toothpaste without NHA for the purpose of remineralization.

Sensitive skin is a frequently mentioned cosmetic complaint. Addition of a biomimetic of neuromediator has recently appeared as a promising new way to cure skin care product problems. This study was aimed to assess the inhibitory effect of a biomimetic lipopeptide derived from proopiomelanocortin (bPOMC) on capsaicin-induced sensory irritation in human volunteers and also to compare its protective effect with that of the well-known anti irritant strontium chloride. The effect of each test compound was studied on 28 selected healthy volunteers with sensitive skin in accordance with a double-blind vehicle-controlled protocol. From day 1 to day 13 each group was applied the test compound (bPOMC or strontium chloride) to one wing of the nose and the corresponding placebo (vehicle) to the other side twice daily. On days 0 and 14, acute skin irritation was induced by capsaicin solution and quantified using clinical stinging test assessments. Following the application of capsaicin solution, sensory irritation was evaluated using a 4-point numeric scale. The sensations perceived before and after treatment (on days 0 and 14) was calculated for the two zones (test materials and vehicle). Ultimately the percentage of variation between each sample and the placebo and also the inhibitory effect of bPOMC compared to that of strontium chloride were reported. Clinical results showed that after two weeks treatment, the levels of skin comfort reported in the group treated with bPOMC were significantly higher than those obtained in the placebo group and the inhibitory effect of bPOMC was about 47% higher than that of strontium chloride. The results of the present study support the hypothesis that biomimetic peptides may be effective on sensitive skin.

Background: Intussusception represents as the invagination of a part of the intestine into itself and is the most common cause of intestinal obstruction in infants and children between 6 months to 3-years-old., Objectives: The objective of this study was to determine the recurrence rate and predisposing factors of recurrent intussusception., Patients and Methods: The medical records of children aged less than 13-years-old with confirmed intussusception who underwent reduction at a tertiary academic care in northern Iran (Mazandran), from 2001 to 2013 were reviewed. Data were extracted and recurrence rate was determined. The two groups were compared by chi square, Fisher, Mann-Whitney and t-test. Diagnosed cases of intussusception consisted of 237 children., Results: Average age of the patients was 19.57 ± 19.43 months with a peak of 3 to 30 months. Male to female ratio was 1.65 and this increased by aging. Recurrence rate was 16% (38 cases). 87 (36.7%) underwent surgery. These were mainly children under one year old. In 71% (40) of episodes recurrence occurred 1 to 7 times within 6 months. The recurrence occurred in 29 (23.5%) children in whom a first reduction was achieved with barium enema (BE) and 5 (5.7%) children who had an operative reduction (P < 0.001) in the first episode. Pathological leading points (PLPs) were observed in 5 cases; 2.6% in recurrence group versus 2% in non-recurrence group (P = 0.91). Three patients had intestinal polyp, 2 patient's lymphoma and Mackle's diverticulum. Age (P = 0.77) and sex (P = 0.38) showed no difference between the two groups. PLPs were observed in 1.4% of children aged 3 months to 5 years. This was 13.3%, in older children (P = 0.02)., Conclusions: The recurrence of intussusception was related to the method of treatment in the first episode and it was 5-fold higher in children with BE than in operative reduction. Recurrent intussusceptions were not associated with PLPs, they were more idiopathic.

Background: Present study aimed to evaluate the prevalence of grades of nutritional status comprising underweight, normal weight, overweight, and obesity as well as other measurable anthropometric indicators of body mass index (BMI) in regard to gender, educational level, and living area among students settled in Isfahan province., Methods: This cross-sectional study was conducted on a sample of 4700 individuals (2349 females and 2351 males) being from 9 to 15 years old, while they were students of either primary school or junior high school. Random cluster method was applied in both urban (84%) and rural (16%) areas of Isfahan province. BMI values were measured and then categorized using reference growth charts from the Centers for Disease Control and Prevention (CDC 2000). Weight-for-age and stature-for-age indices were assessed as well in accordance with CDC growth charts., Results: The overall prevalence of underweight, overweight, and obesity was 13.9, 10.4, and 5.7%, respectively. Boys and students of urban areas showed a higher tendency of obesity and overweight in comparison with girls and rural students respectively. Furthermore, rural students had poorer status in both weight-for-age and stature-for-age indices. In addition, educational level was the only statistically efficacious factor., Conclusions: This study and previous ones demonstrated that children and adolescents' nutritional status, which strongly affect general health status of individuals, should receive more exquisite attention.

Background: It can be concluded from the existing theories that parental education status, by affecting socioeconomical status of families, can impact the incidence of violent behaviors in teenagers. Therefore, this study was conducted aiming at investigating the relationship between parental education and teenagers' knowledge of violent behaviors and their incidences., Methods: For this cross-sectional, descriptive-correlational study, a sample of 5500 teenager students from Isfahan province were selected by random cluster sampling and responded to a 61-item questionnaire. The data collected from by questionnaire was analyzed by Spearman's statistical correlation and multiple regression methods., Results: Most of the students under study (89.1%) were living in cities and the rest were rural dwellers. In terms of gender, female to male ratio was approximately equal (49.8% vs. 50.2%). The statistical results showed that there is a significant positive relationship between practice and knowledge (R = 0.092 and P = 0.00), but there is no significant relationship between parental education and practice and there is a significant relationship between parental education and knowledge (Mothers' education P = 0.00 and R = 0.121 and fathers' education P = 0.00 and R = 0.109). Moreover, there was a positive significant relationship between teenagers' knowledge of violence consequences (P = 0.005 and B = 0.048) violent behavior causes (P = 0.00 B = 0.085) and methods of preventing violent behaviors (P = 0.00 and B = 0.085) with teenagers' practice., Conclusions: Based on the results of the present study that indicates teenagers are less aware of the consequences of violent behavior compared to other subscales of knowledge, it is better that teenagers' education about the violent behaviors are more about the consequences of violent behavior rather than its definitions. Moreover, parental education is related to teenagers' knowledge of the violent behavior so it is better that in various grades more comprehensive and suitable information regarding violent behaviors be presented.

Background: Considering the importance of anger, aggression, violence and other misbehaviours in schoolchildren education, the present study was conducted to evaluate the knowledge and practice of students in Isfahan province regarding violence, in order to figure out the required interventions for violence-reduction., Methods: In a survey during 2008-2009, 5500 junior and senior high school students of Isfahan province were assessed in a multistage sampling process to determine their level of knowledge about various types of violent behaviors, causes of violence, its consequences, and preventive behaviors. Validity and reliability of the data collection tool (questionnaire) were assessed., Results: The study revealed that the mean scores of violent behaviors knowledge, knowledge of violent behavior outcomes, and knowledge of violence preventive behaviors, were 6.6 ± 2.1, 5.5 ± 1.9, and 4.7 ± 1.3, respectively. Sources of violent behaviors in 92% of urban students and 89% of rural students were personal reasons and family behaviors, and 85% of urban and 88% of rural students considered mass media and computer games blameworthy, and the differences were statistically significant in all cases (P < 0.0001). In terms of practice, overall, 69.7% of girls and 84.2% of boys had violent behaviors. Physical and verbal violence were 31.3% and 40.7%in girls, and 66% and 52.8% in boys, respectively (intersexes P values were P < 0.001 and P = 0.7 respectively, and intra-sex P value was P < 0.0001)., Conclusions: Results showed that girls and city dwellers were more aware of recognizing violent behaviors, outcomes, and causes, compared with boys and villagers, and in terms of general practice, violence was observed among boys more than girls. Further complementary studies in this area seem required.

Background: A lot of remedies, mostly plant based, were mentioned in the Persian old pharmacopoeias for promoting of burn and wound healing and tissue repairing. The efficacy of most of these old remedies is unexplored till now. Adiantum capillus-veneris from Adiantaceae family is one of them that was used to treating of some kinds of chronic wounds., Methods: Methanol extract was fractionated to four different partitions that is, hexane, ethyl acetate, n-butanol, and aqueous. The potential of A. capillus-veneris fractions in wound healing or prevention of chronic wounds were evaluated through angiogenesis and fibroblast proliferation, in addition to in vitro tests for protection against damage to fibroblasts by oxygen free radicals., Results: The aqueous part of A. capillus-veneris promoted significant angiogenesis (P < 0.05) through both capillary-like tubular formations and proliferation of endothelial cells in vitro. In addition, in the tests for protection against damage to fibroblasts by oxygen free radicals, aqueous and butanol fractions showed significant protective effects in the concentrations 50, and 500 μg/ml (P < 0.05) in comparison with a control group. In the toxicity testing, it showed weak irritation in the Hen's egg test chorioallantoic membrane (CAM) bioassay at the vascular level on the CAM of the chicken and no significant cytotoxicity in the MTT assays on normal human dermal fibroblasts., Conclusions: Angiogenic effects and protective effects against oxygen free radicals suggested aqueous partition of A. capillus-veneris local application for prevention of late-radiation-induced injuries after radiation therapy and healing of external wounds similar to bedsores and burns.

High-resolution diffusion MRI (dMRI) is useful for resolving complex microstructures in the mouse brain, but technically challenging for in vivo studies due to the long scan time. In this study, selective excitation and a three-dimensional fast imaging sequence were used to achieve in vivo high-resolution dMRI of the mouse brain at 11.7Tesla. By reducing the field of view using spatially selective radio frequency pulses, we were able to focus on targeted brain structures and acquire high angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 0.1mm and 30 diffusion encoding directions in approximately 1h. We investigated the complex tissue microstructures of the mouse hippocampus, cerebellum, and several cortical areas using this localized dMRI approach, and compared the results with histological sections stained with several axonal and dendritic markers. In the mouse visual cortex, the results showed predominately radially arranged structures in an outer layer and tangentially arranged structures in an inner layer, similar to observations from postmortem human brain specimens., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Deodorant products prevent the growth and activity of the degrading apocrine gland bacteria living in the armpit. Common antibacterial agents in the market like triclosan and aluminum salts, in spite of their suitable antibacterial effects, increase the risk of Alzheimer's disease, breast and prostate cancers or induce contact dermatitis. Therefore, plant extracts possessing antibacterial effects are of interest. The aim of the present study was to verify the in vitro antimicrobial effects of different sage extracts against two major bacteria responsible for axillary odor, and to evaluate the deodorant effect of a silicon-based stick containing sage extracts in different densities in humans., Materials and Methods: Different fractions of methanolic extract of Salvia officinalis (sage) were evaluated on a culture of armpit skin surface of volunteers through agar microdilution antimicrobial assay. Then, randomized, double-blind placebo-controlled clinical trial with the best antibacterial fraction was conducted on 45 female healthy volunteers. Participants were treated with a single dose in four groups, each containing 15 individuals: Group 1 (200 μg/mL), 2 (400 μg/mL), 3 (600 μg/mL) of dichloromethane sage extract, and placebo (without extract). A standard sensory evaluation method for the evaluation of deodorant efficacy was used before, and two hours, four hours, and eight hours after single application of a deodorant or placebo (ASTM method E 1207-87 Standard Practice for the Sensory Evaluation of Axillary Deodorancy)., Results: The data were analyzed with two factors relating to densities and time. In 45 participants with a mean [± standard deviation (SD)] age of 61.5±11.8 years, statistically significant within-group differences were observed before and two, four, and eight hours after deodorant treatment for groups 1, 2, and 3. Groups 1, 2, and 3 had a significantly smaller odor score than placebo after two, four, and eight hours (P < 0.001). In a comparison of different deodorant densities, the interaction effect was not significant between deodorant 200 and 400 μg/mL, but was significant between 200 and 600 and between 400 and 600 μg/mL sage extract sticks (P < 0.001). Before running the sensory evaluation of the deodorant sticks on the subjects, a rabbit skin patch test was used to demonstrate that the formulation had no irritants., Conclusion: A single treatment with a stick deodorant containing dichloromethane sage extract of 200, 400, or 600 μg/mL concentrations was effective in reducing the axillary malodor level compared with the control, in healthy subjects.

Native chicken breeding station of Mazandaran was established in 1988 with two main objectives: genetic improvement through selection programs and dissemination of indigenous Mazandarani birds. (Co)variance components and genetic parameters for economically important traits were estimated using (bi) univariate animal models with ASREML procedure in Mazandarani native chicken. The data were from 18 generations of selection (1988-2009). Heritability estimates for body weight at different ages [at hatch (bw1), 8 (bw8), 12 (bw12) weeks of ages and sex maturation (wsm)] ranged from 0.24 ± 0.00 to 0.47 ± 0.01. Heritability for reproductive traits including age at sex maturation (asm); egg number (en); weight of first egg (ew1); average egg weight at 28 (ew28), 30 (ew30), and 32 (ew32) weeks of age; their averages (av); average egg weight for the first 12 weeks of production (ew12); egg mass (em); and egg intensity (eint) varied from 0.16 ± 0.01 to 0.43 ± 0.01. Generally, the magnitudes of heritability for the investigated traits were moderate. However, egg production traits showed smaller heritability compared with growth traits. Genetic correlations among egg weight at different ages were mostly higher than 0.8. On the one hand, body weight at different ages showed positive and relatively moderate genetic correlations with egg weight traits (ew1, ew28, ew30, ew32, ew12, and av) and varied from 0.30 ± 0.03 to 0.59 ± 0.02. On the other hand, low negative genetic correlations were obtained between body weight traits (bw1, bw8, bw12, and wsm) and egg number (en). Also, there is low negative genetic correlation (-24 ± 0.04 to -29 ± 0.05) between egg number and egg weight. Therefore, during simultaneous selection process for both growth and egg production traits, probable reduction in egg production due to low reduction in egg number may be compensated by increases in egg weight.

Neuropeptide Y (NPY) and gonadotrophin-releasing hormone receptor (GnRHR) are two candidate genes with a wide variety of physiological functions in growth and especially in reproduction processes. We examined the association of one SNP from each of these genes with growth- and egg production-related traits in Mazandaran native chickens. Two hundred and six individuals were genotyped by PCR-RFLP. Marker-trait association analyses were performed using both breeding value and phenotypic information. The data came from 18 successive generations of selection at a Mazandaran native chicken breeding station in Iran. Data were analyzed with a univariate animal model in an ASREML procedure to estimate breeding values of the birds for these traits. Two alleles were found for both genes, A and a alleles for GnRHR, with frequencies of 0.614 and 0.386, B and b alleles for NPY, with frequencies of 0.780 and 0.221, respectively. The additive genetic effects of the GnRHR gene on egg number and egg mass were significant. Also, body weight at sexual maturity was significantly influenced by the NPY gene. We conclude that GnRHR and NPY genes are associated with egg production and growth traits, respectively.

In the management and evaluation of asthma, simple instruments for measurements of peak expiratory flow rate (PEFR) are necessary. The aim of this study was to determine normal PEFR of the healthy children in Babol, Iran. This study was randomly done on 1050 students (primary and secondary schools) in Babol. Mini-Wright peak flow meter was used for measurement of PEFR. The range of age, weight and height were defined. Information was statistically analyzed by SPSS, T- Test and R2 and due to formula with regression. Mean age of 1050 students (525 male and 525 female) who participated in this study was 10.26 years. The mean of PEFR was 262.35+/-71.97 L/Min. Obtained PEFR with all anthropometrics variants indicate a high correlation. Correlation between PEFR and height was more significant and between PEFR and weight was lower, and according to importance of height and age, formulas suggested for prediction of PEFR in females {(agex4.8)+ (heightx0.6)-25)} and in males ({(agex1.7)+ (heightx2.1)-208)}. The results of this study can determine normal PEFR and it can be useful for treatment and monitoring of children with asthma who live in this region.

Multicenter clinical trials for therapy evaluation of rare diseases are necessary. A digital imaging network improves the ability to share information between collaborating institutions for adrenoleukodystrophy. The DICOM 3.0 standard is used to move images over the Internet from contributing sites to the central clinical database and on to the reviewing physicians' workstations. Patient confidentiality and data integrity are ensured during transmission using virtual private network technology. Fifteen sites are participating in the network. Of these sites, 6 use the proposed protocol. The other 9 sites have either security policy issues or technical considerations that dictate alternative protocols. Network infrastructure, Internet access, image management practices, and security policies vary significantly between sites. Successful implementation of a multicenter digital imaging network requires flexibility in the implementation of network connectivity. Flexibility increases participation as well as complexity of the network.