A Protocol for Management of the Hairs Problem in Oral Cavity Reconstruction by Submental Flap

Abstract

Background

Submental flap is a useful aid in maxillofacial reconstruction. For intraoral usage the hairs in male patients will create some problems.

Materials and Methods

In a retrospective study, patients in whom submental flap had been used for reconstruction of orofacial region between 2007 and 2013, in the Mashhad University, Ghaem Hospital, were included. The ways in which the problem of hairs was solved in male patients were evaluated.

Results

There were 42 patients in whom submental flap was used for orofacial reconstruction. Sixty percent were males. Three ways had been used for management of intraoral hairs: radiotherapy (9 patients), second surgery (2 patients) and flap de-epithelialization (13 patients).

Conclusion

Deepithelialized variant of submental flap is the best option when submental flap is used for oral cavity reconstruction in male patients. Flap thickness, age, race and postoperative radiotherapy can have strong influence on this strategy.

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Congenital Hypertonia of the Temporalis Leading to Trismus Since Birth

Abstract

Congenital trismus is quite rare especially when its etiology is not the usual. In our case report an 8 year old female patient with no history of forcep delivery, no history of trauma or infection and a non syndromic presents with trismus since birth. After thorough examination we could conclude that the cause is due to hypertonia of the temporalis muscle and its etiology is discussed.

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The utility of p16 immunostaining in fine needle aspiration in p16-positive head and neck squamous cell carcinoma

Publication date: August 2016
Source:Human Pathology, Volume 54
Author(s): Bin Xu, Ronald Ghossein, Jason Lane, Oscar Lin, Nora Katabi
Many patients with human papillomavirus (HPV)–related head and neck squamous cell carcinoma present initially with cervical nodal metastasis. Fine needle aspiration (FNA) of the nodal disease might be the only diagnostic material available for p16 immunohistochemistry (IHC) and HPV testing. The current study aims to evaluate p16 IHC in FNA and establish guidelines for its interpretation. The percentage and intensity of p16 IHC staining were examined in 60 matched FNA and surgical cases. Cytomorphologic features were included in the analysis. p16 IHC staining was correlated with the results seen in the surgical specimens and with HPV in situ hybridization (ISH). Analysis of different thresholds demonstrated that the threshold of 10% p16 tumor cell positivity had the best overall concordance rate with surgical p16 IHC (κ = 0.650) and with FNA HPV-ISH (κ = 0.714). Applying the recommended p16 positivity threshold for surgical specimens (70%) on FNA materials resulted in low sensitivity (39%) and low negative predictive value (26%). In comparison with p16 IHC in surgical specimens, 6/46 FNA cases (13%) were falsely negative for p16. All 6 cases were associated with necrotic background, two (33%) lacked large tumor clusters, and one (17%) had low cellularity. The recommended threshold for p16 IHC on surgical specimens should not be used in cytology materials. The cutoff value for p16 immunostain in FNA specimens showing best results in our series is 10%. When p16 IHC is negative in FNA specimens, a repeat stain on a surgical specimen is recommended to avoid a false-negative diagnosis.



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Real-World Effectiveness and Safety of a Live-Attenuated Herpes Zoster Vaccine: A Comprehensive Review

Abstract

Abstract

Herpes zoster (HZ) is a common, painful and debilitating disease caused by the reactivation of latent varicella-zoster virus in ganglia. This clinical event occurs more frequently in the elderly and those who are immunocompromised. The most common complication of HZ is post-herpetic neuralgia (PHN) which is responsible for the highest HZ-related burden of illness and is challenging to treat. Due to the important clinical and economic impact of HZ and PHN, and the suboptimal treatments that are currently available, HZ vaccination is an important approach to reduce the burden of illness. Currently, one-dose, live-attenuated vaccine is licensed in the United States and Europe to prevent HZ and it is included in some national immunization programs. The clinical efficacy, safety and tolerability of the vaccine has been demonstrated in two large phase III clinical trials, involving more than 38,000 and 22,000 individuals aged ≥60 and 50–59 years, respectively. This comprehensive review summarizes the extensive "real-world" effectiveness and safety data from both immunocompetent and immunocompromised individuals. These data confirm those from the clinical trials, supporting the use of HZ vaccine in clinical practice and provide evidence that the current recommendations for immunocompromised individuals should be revised.

Funding

Funding for the editorial assistance, article processing charges, and open access fee for this publication was provided by Sanofi Pasteur MSD.

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Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Christopher Schutta, José Barrera, Melia Pisano, Laszlo Zsak, Marvin J. Grubman, Gregory A. Mayr, Mauro P. Moraes, Barbara J. Kamicker, David A. Brake, Damodar Ettyreddy, Douglas E. Brough, Bryan T. Butman, John G. Neilan
The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10⁸ to 2.1×10¹¹ particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R²=0.97) and viremia (R²=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R²=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge.



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Control of Ixodes ricinus and Dermacentor reticulatus tick infestations in rabbits vaccinated with the Q38 Subolesin/Akirin chimera

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Marinela Contreras, José de la Fuente
Diseases transmitted by ticks greatly impact human and animal health and their control is important for the eradication of tick-borne diseases. Vaccination is an environmentally friendly alternative for tick control. Recent results have suggested that Subolesin/Akirin (SUB/AKR) are good candidate antigens for the control of arthropod vector infestations. Here, we describe the effect of vaccination with the Q38 chimera containing SUB/AKR conserved protective epitopes on Ixodes ricinus and Dermacentor reticulatus tick larval mortality, feeding and molting. We demonstrated that Q38 vaccination had an efficacy of 99.9% and 46.4% on the control of I. ricinus and D. reticulatus larvae by considering the cumulative effect on reducing tick survival and molting. The effect of the Q38 vaccine on larval feeding and molting is essential to reduce tick infestations and supports that Q38 might be a candidate universal antigen for the control of multiple tick species that can infest the same host.



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Editorial Board/Aims and Scope

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27





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A population profile of measles susceptibility in Tianjin, China

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Matthew L. Boulton, Xiexiu Wang, Ying Zhang, JoLynn P. Montgomery, Abram L. Wagner, Bradley F. Carlson, Yaxing Ding, Xiaoyan Li, Brenda Gillespie, Xu Su
BackgroundMeasles is a highly infectious illness requiring herd immunity of 95% to interrupt transmission. Measles is targeted for elimination in China, which has not reached elimination goals despite high vaccination coverage. We developed a population profile of measles immunity among residents aged 0–49 years in Tianjin, China.MethodsParticipants were either from community population registers or community immunization records. Measles IgG antibody status was assessed using dried blood spots. We examined the association between measles IgG antibody status and independent variables including urbanicity, sex, vaccination, measles history, and age.Results2818 people were enrolled. The proportion measles IgG negative increased from 50.7% for infants aged 1 month to 98.3% for those aged 7 months. After 8 months, the age of vaccination eligibility, the proportion of infants and children measles IgG negative decreased. Overall, 7.8% of participants 9 months of age or older lacked measles immunity including over 10% of those 20–39 years. Age and vaccination status were significantly associated with measles IgG status in the multivariable model. The odds of positive IgG status were 0.337 times as high for unvaccinated compared to vaccinated (95% CI: 0.217, 0.524).ConclusionsThe proportion of persons in Tianjin, China immune to measles was lower than herd immunity threshold with less than 90% of people aged 20–39 years demonstrating protection. Immunization programs in Tianjin have been successful in vaccinating younger age groups although high immunization coverage in infants and children alone would not provide protective herd immunity, given the large proportion of non-immune adults.



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Emergence of antigenic variants within serotype A FMDV in the Middle East with antigenically critical amino acid substitutions

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Mana Mahapatra, Bob Statham, Yanmin Li, Jef Hammond, David Paton, Satya Parida
A new immunologically distinct strain (A-Iran-05) of foot-and-mouth disease virus serotype A emerged in the Middle East in 2003 that replaced the previously circulating strains (A-Iran-96 and A-Iran-99) in the region. This resulted in introduction of a new vaccine of this strain (A/TUR/2006) in 2006. Though this vaccine strain has been predominantly used to control FMD in the region, recent viruses isolated in 2012 and 2013 have shown antigenic drift and a poor match with it. In this study, we report the antigenic matching results and capsid sequence data of currently circulating viruses belonging to the SIS-10 and SIS-12 sub-lineages of A-Iran-05 (isolated in 2012 and 2013), highlighting the inadequacy of the currently used serotype A vaccines. Implications of these results in the context of FMD control in the Middle East are discussed.



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Effect of high and low levels of maternally derived antibodies on porcine circovirus type 2 (PCV2) infection dynamics and production parameters in PCV2 vaccinated pigs under field conditions

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Hua Feng, Joaquim Segalés, Lorenzo Fraile, Sergio López-Soria, Marina Sibila
The present study aimed to compare the efficacy of a porcine circovirus type 2 (PCV2) commercial vaccine in terms of average daily weight gain (ADWG) as well as infection dynamics in pigs with different maternally derived antibody (MDA) levels. A total of 337 animals from a PCV2 subclinically infected farm were distributed into two groups based on weight and PCV2 antibody levels (high [H] or low [L]) at 2 weeks of age. One week later, these animals were subdivided in four groups according to the treatment received. Vaccinated pigs (H-V and L-V) received 1mL of a commercial vaccine and NV (H-NV and L-NV) received 1mL of PBS. All piglets were subsequently bled at 7, 12, 18, 22 and 25 weeks of age and weighted at 12 and 25 weeks of age. V animals showed significantly lower PCV2 infection rates and viral load as well as higher ELISA S/P ratios and ADWG than NV ones. Compared with H-V piglets, L-V pigs showed numerically lower PCV2 infection rates, lower area under the curve of viral load, an earlier seroconversion and a numerically, but not significantly, higher ADWG. In this study, MDA did not seem to interfere with the effect of PCV2 vaccination on ADWG. However, only when a small subpopulation of pigs with the highest ELISA S/P ratios at vaccination was considered, an apparent interference of vaccine efficacy on ADWG was noticed. Therefore, the impact of the putative interference under field conditions is probably negligible for most farms.



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Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Mami Taniuchi, James A. Platts-Mills, Sharmin Begum, Md Jashim Uddin, Shihab U. Sobuz, Jie Liu, Beth D. Kirkpatrick, E. Ross Colgate, Marya P. Carmolli, Dorothy M. Dickson, Uma Nayak, Rashidul Haque, William A. Petri, Eric R. Houpt
BackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647.



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Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes (Phoenicopterus spp.)

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Hugo Fernández-Bellon, Júlia Vergara-Alert, Vanessa Almagro, Raquel Rivas, Azucena Sánchez, María Carmen Martínez, Natàlia Majó, Núria Busquets, Antonio Ramis
Avian influenza (AI) can represent a threat to endangered wild birds, as demonstrated with the H5N1 highly pathogenic AI (HPAI) outbreaks. Vaccination against AI using inactivated H5-vaccines has been shown to induce humoral immune response in zoo bird species. In this study, the long-term efficacy of H5-vaccination was evaluated in flamingoes from Barcelona Zoo. Specific H5-antibody titres were maintained at high levels (geometric mean titres ≥32) for over 7 years after vaccination, both against the H5N9 and H5N3 vaccine strains, as well as H5N3 and H5N1 reference strains. In addition the breadth of the immune response was also studied by testing antibody production against H1-, H3-, H4-, H7-, and H10-subtypes. It was observed that most flamingoes presented specific antibodies against H1 virus subtypes, but titres to the other HA-subtypes were rarely detected. We show that AI-vaccines can induce immunity lasting seven years in flamingoes, which suggests that vaccination can provide long term protection from HPAI outbreaks in zoo birds.



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Immune effects of the vaccine of live attenuated Aeromonas hydrophila screened by rifampicin on common carp (Cyprinus carpio L)

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Xinyu Jiang, Chao Zhang, Yanjing Zhao, Xianghui Kong, Chao Pei, Li Li, Guoxing Nie, Xuejun Li
Aeromonas hydrophila, as a strong Gram-negative bacterium, can infect a wide range of freshwater fish, including common carp Cyprinus carpio, and cause the huge economic loss. To create the effective vaccine is the best way to control the outbreak of the disease caused by A. hydrophila. In this study, a live attenuated A. hydrophila strain, XX1LA, was screened from the pathogenic A. hydrophila strain XX1 cultured on medium containing the antibiotic rifampicin, which was used as a live attenuated vaccine candidate. The immune protection of XX1LA against the pathogen A. hydrophila in common carp was evaluated by the relative percent survival (RPS), the specific IgM antibody titers, serum lysozyme activity and the expression profiles of multiple immune-related genes at the different time points following immunization. The results showed that the variable up-regulations of the immune-related genes, such as the pro-inflammatory cytokine IL-1β, the chemokine IL-10 and IgM, were observed in spleen and liver of common carp injected in the vaccines with the formalin-killed A. hydrophila (FKA) and the live attenuated XX1LA. Specific antibody to A. hydrophila was found to gradually increase during 28 days post-vaccination (dpv), and the RPS (83.7%) in fish vaccinated with XX1LA, was significant higher than that (37.2%) in fish vaccinated with FKA (P<0.05) on Day 28 after challenged by pathogen. It was demonstrated that the remarkable immune protection presented in the group vaccinated with XX1LA. During the late stage of 4-week immunization phase, compared with FKA and the control, specific IgM antibody titers significantly increased (P<0.05) in the XX1LA group. The activity of the lysozyme in serum indicated no significant change among three groups. In summary, the live attenuated bacterial vaccine XX1LA, screened in this study, indicates the better protect effect on common carp against A. hydrophila, which can be applied in aquaculture of common carp to prevent from the disease outbreak in the future.



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Heparan sulfates targeting increases MHC class I- and MHC class II-restricted antigen presentation and CD8+ T-cell response

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Delphine Knittel, Adeline Gadzinski, Stéphane Hua, Jordan Denizeau, Alexandra Savatier, Philippe de la Rochère, Jean-Claude Boulain, Sebastian Amigorena, Eliane Piaggio, Christine Sedlik, Michel Léonetti
Heparan sulfates (HS) are carbohydrate moieties of HS proteoglycans (HSPGs). They often represent alternative attachment points for proteins or microorganisms targeting receptors. HSPGs, which are ubiquitously expressed, thereby participate in numerous biological processes. We previously showed that MHC class II-restricted antigen presentation is increased when antigens are coupled to HS ligands, suggesting that HSPGs might contribute to adaptive immune responses. Here, we examined if HSPG targeting influences other aspects of immune responses. We found that coupling of an HS ligand to the antigen increases antigen presentation to CD4⁺ and CD8⁺ T-cells after antigen targeting to membrane immunoglobulins or to MHC-II molecules. Moreover, this increased stimulating capacity correlates with an enhanced CD8⁺ immune response in mice. Last, animals control more effectively the growth of Ova-expressing tumour cells when they are immunized with an Ova construct targeting HSPGs and MHC-II molecules. Our results indicate that ubiquitous molecules can influence both MHC class I- and MHC class II-restricted antigen presentation and behave as co-receptors during T-cell stimulation. Moreover, they suggest that tumour-antigens endowed with the ability to target both HSPGs and MHC-II molecules could be of value to increase CD8⁺ immune response and control tumour-growth, opening new perspectives for the design of highly immunogenic protein-based vaccines.



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CRACC-targeting Fc-fusion protein induces activation of NK cells and DCs and improves T cell immune responses to antigenic targets

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Yasser A. Aldhamen, David P.W. Rastall, Weimin Chen, Sergey S. Seregin, Cristiane Pereira-Hicks, Sarah Godbehere, Norbert E. Kaminski, Andrea Amalfitano
The CD2-like receptor activating cytotoxic cell (CRACC) receptor is a member of the SLAM family of receptors that are found on several types of immune cells. We previously demonstrated that increasing the abundance of the adaptor protein EAT-2 during vaccination enhanced innate and adaptive immune responses to vaccine antigens. Engagement of the CRACC receptor in the presence of the EAT-2 adaptor generally results in immune cell activation, while activating CRACC signaling in cells that lack EAT-2 adaptor inhibits their effector and regulatory functions. As EAT-2 is the only SAP adaptor that interacts with the CRACC receptor, we hypothesized that technologies that specifically modulate CRACC signaling during vaccination may also improve antigen specific adaptive immune responses. To test this hypothesis, we constructed a CRACC-targeting Fc fusion protein and included it in vaccination attempts. Indeed, mice co-vaccinated with the CRACC-Fc fusion protein and an adenovirus vaccine expressing the HIV-Gag protein had improved Gag-specific T cell responses, as compared to control mice. These responses are characterized by increased numbers of Gag-specific tetramer+ CD8+ T cells and increases in production of IFNγ, TNFα, and IL2, by Gag-specific CD8+ T cells. Moreover, our results revealed that use of the CRACC-Fc fusion protein enhances vaccine-elicited innate immune responses, as characterized by increased dendritic cells (DCs) maturation and IFNγ production from NK cells. This study highlights the importance of CRACC signaling during the induction of an immune response generally, and during vaccinations specifically, and also lends insight into the mechanisms underlying our prior results noting EAT-2-dependent improvements in vaccine efficacy.



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Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Hana Hakim, Kim J. Allison, Lee-Ann Van de Velde, Li Tang, Yilun Sun, Patricia M. Flynn, Jonathan A. McCullers
BackgroundApproaches to improve the immune response of immunocompromised patients to influenza vaccination are needed.MethodsChildren and young adults (3–21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine.ResultsEighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively).ConclusionHD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV.



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Phase I, randomized, observer-blind, placebo-controlled studies to evaluate the safety, reactogenicity and immunogenicity of an investigational non-typeable Haemophilus influenzae (NTHi) protein vaccine in adults

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Geert Leroux-Roels, Pierre Van Damme, Wouter Haazen, Sepehr Shakib, Magalie Caubet, Emmanuel Aris, Jeanne-Marie Devaster, Mathieu Peeters
BackgroundNon-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD], E [PE] and Pilin A [PilA]) in two observer-blind phase I studies.MethodsIn the first study (NCT01657526), 48 healthy 18–40 year-olds received two vaccine formulations (10 or 30μg of each antigen [PD and a fusion protein PE-PilA]) or saline placebo at months 0 and 2. In the second study (NCT01678677), 270 50–70 year-olds, current or former smokers, received eight vaccine formulations (10 or 30μg antigen/dose non-adjuvanted or adjuvanted with alum, AS01E or AS04C) or saline placebo at months 0, 2 and 6 (plain and alum-adjuvanted groups) and at months 0 and 2 (AS-adjuvanted groups). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the studies. Humoral and antigen-specific T-cell immunity (in study 2 only) responses were assessed up to 12 months post-vaccination.ResultsObserved reactogenicity was highest in the AS-adjuvanted groups but no safety concerns were identified with any of the NTHi vaccine formulations. One fatal SAE (cardiac arrest) not considered related to vaccination, and one pIMD (non-serious psoriasis) in the Placebo group, were reported post-dose 3 in Study 2. All formulations generated a robust antibody response while the AS01-adjuvanted formulations produced the highest humoral and cellular immune responses.ConclusionThis study confirms that the NTHi vaccine formulations had an acceptable reactogenicity and safety profile and were immunogenic in adults. These results justify further clinical development of this NTHi vaccine candidate.



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Characterization of serum antibodies from women immunized with Gardasil: A study of HPV-18 infection of primary human keratinocytes

Publication date: 8 June 2016
Source:Vaccine, Volume 34, Issue 27
Author(s): Hsu-Kun Wang, Qing Wei, Zina Moldoveanu, Warner K. Huh, Huong Lan Vu, Thomas R. Broker, Jiri Mestecky, Louise T. Chow
The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are based on DNA-free virus-like particles (VLPs) composed of the major capsid protein L1 of HPV-16, -18, -6 and -11 (Gardasil) or HPV-16 and -18 (Cervarix). Sera from vaccinated animals effectively prevent HPV pseudovirions to infect cell lines and mouse cervical epithelia. Both vaccines have proven to be highly protective in people. HPV pseudovirions are assembled in HEK293TT cells from matched L1 and L2 capsid proteins to encapsidate a reporter gene. Pseudovirions and genuine virions have structural differences and they infect cell lines or primary human keratinocytes (PHKs) with different efficiencies. In this study, we show that sera and isolated IgG from women immunized with Gardasil prevent authentic HPV-18 virions from infecting PHKs, whereas non-immune sera and purified IgG thereof are uniformly ineffective. Using early passage PHKs, neutralization is achieved only if immune sera are added within 2–4h of infection. We attribute the timing effect to a conformational change in HPV virions, thought to occur upon initial binding to heparan sulfate proteoglycans (HSPG) on the cell surface. This interpretation is consistent with the inability of immune IgG bound to or taken up by PHKs to neutralize the virus. Interestingly, the window of neutralization increases to 12–16h in slow growing, late passage PHKs, suggestive of altered cell surface molecules. In vivo, this window might be further lengthened by the time required to activate the normally quiescent basal cells to become susceptible to infection. Our observations help explain the high efficacy of HPV vaccines.



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Up-regulation of BSEP and MRP2 by Calculus Bovis administration in 17α-ethynylestradiol-induced cholestasis: Involvement of PI3K/Akt signaling pathway

Publication date: 22 August 2016
Source:Journal of Ethnopharmacology, Volume 190
Author(s): Tao Wu, Qianrui Zhang, Jingjing Li, Hong Chen, Ji Wu, Hongping Song
Ethnopharmacology relevanceCalculus Bovis, also known as Niuhuang, is a rare traditional Chinese medicine that has been widely used in China for 2000 years in pharmacology for sedation, anti-spasm, relieving fever, diminishing inflammation and recovering gallbladder functions.Aim of the studyThis study aimed to investigate the choleretic potential and molecular responses in rats to Calculus Bovis (CB) administration after 17α-ethynylestradiol (EE)-induced cholestasis.Material and methodsCB (50 and 100mg/kg per day) was intragastrically (i. g.) given to experimental rats for five consecutive days in coadministration with EE (5mg/kg daily for five days, s.c.). The levels of serum biomarkers were determined biochemically. The histopathology of the liver tissue was evaluated. Expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were studied by western blot and immunohistochemical assay. The expression of Akt and phospho-Akt (pAkt) were also measured by western blot.ResultsIn response to EE, CB treatment significantly prevented an increase in serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT) and total bilirubin (TBIL). CB treatment also repaired tissue lesions caused by EE. Western blots showed that EE significantly decreased the protein expression of BSEP and MRP2. EE also dramatically increased levels of pAkt and decreased levels of Akt. Compared to the EE group, CB treatment increased levels of hepatic BSEP and MRP2 while pAkt levels decreased and Akt levels increased. Immunohistochemistry also indicated that EE decreased the expression of BSEP and MRP2. LY294002 is a selective PI3K inhibitor and showed similar beneficial effects as CB. Decreased expression of BSEP and MRP2 caused by EE were also prevented by LY294002 treatment.ConclusionCalculus Bovis administration can alleviate liver injury and up-regulate the expression of BSEP and MRP2 in 17α-ethynylestradiol-induced cholestasis by a mechanism that may involve inhibiting the activated PI3K/Akt signaling pathway.

Graphical abstract

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Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species

Publication date: 22 August 2016
Source:Journal of Ethnopharmacology, Volume 190
Author(s): Ashish Kumar Jena, Karan Vasisht, Neetika Sharma, Ramdeep Kaur, Mamta Sachdeva Dhingra, Maninder Karan
Ethnopharmacological relevanceBenign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species.Aim of the studyIn the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents.Materials and methodsThe antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC.ResultsThe Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH.ConclusionsThese findings are suggestive of a meaningful inhibitory effect of testosterone induced BPH by the bark of different species of Prunus in the order of P. domestica, P. persica, P. amygdalus, P. cerasoides and P. armeniaca with an efficacy of P. domestica comparable to P. africana and can be used as the potential backup of Pygeum for the management of BPH.

Graphical abstract

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Rheumatoid arthritis onset in postmenopausal women: Does the ACPA seropositive subset result from genetic effects, estrogen deficiency, skewed profile of CD4+ T-cells, and their interactions?

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Rony Sapir-Koren, Gregory Livshits
Rheumatoid arthritis (RA) incidence displays a differentiated age-dependent female-to-male ratio in which women outnumber men. Evidence that the peak incidence of RA in women coincides with menopause age, suggests a potential estrogenic role to disease etiology. Estrogens exert physiologically both stimulatory and inhibitory effects on the immune system. Epidemiologic and animal model studies with estrogen deprivation or supplementation suggested estrogens as to play, mainly, a protective role in RA immunopathology. In this review, we propose that some yet unidentified disturbances associated with estrogen circulating levels, differentiated by the menopausal status, play a major role in women's RA susceptibility. We focus on the interaction between estrogen deprivation and genetic risk alleles for anti-citrullinated protein antibodies (ACPA) seropositive RA, as a major driving force for increased immune reactivity and RA susceptibility, in postmenopausal women. This opens up new fields for research concerning the association among different irregular estrogenic conditions, the cytokine milieu, and age/menopausal status bias in RA.



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Neonatal overfeeding induces early decline of the ovarian reserve: Implications for the role of leptin

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Luba Sominsky, Ilvana Ziko, Alita Soch, Jeremy T. Smith, Sarah J. Spencer
Early life nutrition is crucial for reproduction. Overweight and obese girls are more likely to experience early menarche, increasing the risk of adult disease. We have previously demonstrated neonatal overfeeding in the rat leads to accelerated growth, early puberty and increased circulating levels of leptin, an adipocyte-derived hormone that regulates puberty. However, the long-term consequences of accelerated puberty and metabolic dysfunction on ovarian reserve are unknown. Here we show that neonatal overfeeding reduced the number of ovarian follicles in adult rats; specifically, the primordial follicle pool was reduced compared to controls. The reduction of ovarian reserve coincided with a diminished release of pituitary gonadotropins at ovulation and altered expression of ovarian markers important for follicular recruitment and survival. These changes were associated with increased levels of ovarian leptin and its receptor. Postnatal administration of leptin antagonist did not reverse the weight gain induced by early life overfeeding, but rescued the decline in the primordial follicle pool and abolished the differences in circulating leptin and gonadotropins. Our findings suggest that the acute effects of elevated circulating leptin may be responsible for the long-term reproductive outcomes after neonatal overfeeding, leading to premature ovarian ageing and changes in reproductive efficiency.



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Upregulation of long noncoding RNA LOC100507661 promotes tumor aggressiveness in thyroid cancer

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Daham Kim, Woo Kyung Lee, Seonhyang Jeong, Mi-Youn Seol, Hyunji Kim, Kyung-Sup Kim, Eun Jig Lee, Jandee Lee, Young Suk Jo
Recent advances in next-generation sequencing have revealed a variety of long noncoding RNAs (lncRNAs). However, studies of lncRNAs are at a very early stage, our knowledge of the biological functions and clinical implications remains limited. To investigate the roles of lncRNAs in thyroid cancers, we verified 56 lncRNAs identified as potential cancer-promoting genes in a previous study that analyzed 2394 tumor SNP arrays from 12 types of cancer. Based on verified sequence information in NCBI and Ensembl, we ultimately selected three candidate lncRNAs for detailed analysis. One of the candidates, LOC100507661, was strongly upregulated in thyroid cancer tissues relative to paired contralateral normal tissue. LOC100507661 was easily detectable in papillary and anaplastic thyroid cancer cell lines such as TPC1, BCPAP, C643, and 8505C, but not in the follicular thyroid cancer cell line FTC133. Stable overexpression of LOC100507661 promoted cell proliferation, migration, and invasion of thyroid cancer cells. Lymph node metastasis and BRAF V600E mutations were more frequent in papillary thyroid cancers with high LOC100507661 expression. Our data demonstrate that LOC100507661 expression is elevated in human thyroid cancer and may play a critical role in thyroid carcinogenesis.



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Oxidative stress and the subcellular localization of the telomerase reverse transcriptase (TERT) in papillary thyroid cancer

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Marina Muzza, Carla Colombo, Valentina Cirello, Michela Perrino, Leonardo Vicentini, Laura Fugazzola
During hormonogenesis, thyrocytes are physiologically exposed to high levels of oxidative stress (OS) which could either be involved in the pathogenesis of thyroid cancer or exert a cytotoxic effect. We analyzed the oxidative status of papillary thyroid cancer (PTC) both directly, by measuring H2O2 generation by NADPH oxidases (NOXs), and indirectly, by evaluating the antioxidant activity of glutathione peroxidase (GPX), which neutralizes H2O2 excess, and the lipid peroxidation (LP). Moreover, we investigated the subcellular localization of telomerase reverse transcriptase (TERT), and the H2O2 levels in the mitochondria of tumor and normal tissues.The calcium-dependent and independent H2O2 generation activity was significantly higher in tumors than in normal tissues. The GPX activity was higher in PTCs than in normal tissues, and, consistently, no differences were found in LP levels. Moreover, while TERT nuclear expression was similar in tumor and normal tissues, the mitochondrial localization was significantly higher in tumors. At the mitochondrial level, no differences were found in H2O2 generation between tumor and normal tissues.In conclusion, present data demonstrate that the intracellular H2O2 generation by NOXs is significantly higher in PTCs than in normal thyroid tissues. The increased GPX activity found in tumors counteracts the potential cytotoxic effects of high OS exposure. The significantly higher mitochondrial localization of TERT in tumors is consistent with its shuttling from the nucleus upon exposure to high OS. Finally, mitochondrial OS was not significantly different in tumors and normal tissues, supporting the postulated role of mitochondrial TERT in the control of local H2O2 production.



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Estrogen receptor profiling and activity in cardiac myocytes

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Emily K. Pugach, Christa L. Blenck, Joseph M. Dragavon, Stephen J. Langer, Leslie A. Leinwand
Estrogen signaling appears critical in the heart. However a mechanistic understanding of the role of estrogen in the cardiac myocyte is lacking. Moreover, there are multiple cell types in the heart and multiple estrogen receptor (ER) isoforms. Therefore, we studied expression, localization, transcriptional and signaling activity of ERs in isolated cardiac myocytes. We found only ERα RNA (but no ERβ RNA) in cardiac myocytes using two independent methods. The vast majority of full-length ERα protein (ERα66) localizes to cardiac myocyte nuclei where it is competent to activate transcription. Alternate isoforms of ERα encoded by the same genomic locus (ERα46 and ERα36) have differential transcriptional activity in cardiac myocytes but also primarily localize to nuclei. In contrast to other reports, no ERα isoform is competent to activate MAPK or PI3K signaling in cardiac myocytes. Together these data support a role for ERα at the level of transcription in cardiac myocytes.



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Up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis in human papillary thyroid cancer cells

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Xiao-Mei Mo, Li Li, Ping Zhu, Yu-Jie Dai, Ting-Ting Zhao, Ling-Yao Liao, George G. Chen, Zhi-Min Liu
17β-estradiol (E2) has been suggested to play a role in the development and progression of papillary thyroid cancer. Heat shock protein 27 (Hsp27) is a member of the Hsp family that is responsible for cell survival under stressful conditions. Previous studies have shown that the 5′-promoter region of Hsp27 gene contains a specificity protein-1 (Spl) and estrogen response element half-site (ERE-half), which contributes to Hsp27 induction by E2 in breast cancer cells. However, it is unclear whether Hsp27 can be up-regulated by E2 and which estrogen receptor (ER) isoform and tethered transcription factor are involved in this regulation in papillary thyroid cancer cells. In the present study, we demonstrated that Hsp27 can be effectively up-regulated by E2 at mRNA and protein levels in human K1 and BCPAP papillary thyroid cancer cells which have more than two times higher level of ERα than that of ERβ. The up-regulation of Hsp27 by E2 is mediated by ERα/Sp1 and ERβ has repressive effect on this ERα/Sp1-mediated up-regulation of Hsp27. Moreover, we showed that the up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis through interaction with procaspase-3. Targeting this pathway may be a potential strategy for therapy of papillary thyroid cancer.



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Urinary metabolomic profiling in mice with diet-induced obesity and type 2 diabetes mellitus after treatment with metformin, vildagliptin and their combination

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Helena Pelantová, Martina Bugáňová, Martina Holubová, Blanka Šedivá, Jana Zemenová, David Sýkora, Petra Kaválková, Martin Haluzík, Blanka Železná, Lenka Maletínská, Jaroslav Kuneš, Marek Kuzma
Metformin, vildagliptin and their combination are widely used for the treatment of diabetes, but little is known about the metabolic responses to these treatments. In the present study, NMR-based metabolomics was applied to detect changes in the urinary metabolomic profile of a mouse model of diet-induced obesity in response to these treatments. Additionally, standard biochemical parameters and the expression of enzymes involved in glucose and fat metabolism were monitored. Significant correlations were observed between several metabolites (e.g., N-carbamoyl-β-alanine, N1-methyl-4-pyridone-3-carboxamide, N1-methyl-2-pyridone-5-carboxamide, glucose, 3-indoxyl sulfate, dimethylglycine and several acylglycines) and the area under the curve of glucose concentrations during the oral glucose tolerance test. The present study is the first to present N-carbamoyl-β-alanine as a potential marker of type 2 diabetes mellitus and consequently to demonstrate the efficacies of the applied antidiabetic interventions. Moreover, the elevated acetate level observed after vildagliptin administration might reflect increased fatty acid oxidation.



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An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Francisco Javier Ruiz-Ojeda, Concepción María Aguilera, Azahara Iris Rupérez, Ángel Gil, Carolina Gomez-Llorente
The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases.



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Benzyl butyl phthalate induces epigenetic stress to enhance adipogenesis in mesenchymal stem cells

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Ravi Sonkar, Catherine A. Powell, Mahua Choudhury
Endocrine disruptors, phthalates, may have contributed to recent global obesity health crisis. Our study investigated the potential of benzyl butyl phthalate (BBP) to regulate the mesenchymal stem cell epigenome to drive adipogenesis. BBP exposure enhanced lipid accumulation and adipogenesis in a dose-dependent manner compared to control (P < 0.001). Adipogenesis markers, PPARγ (P < 0.001), C/EBPα (P < 0.01), and aP2 (P < 0.001) were significantly upregulated by increasing concentrations of BBP when compared to DMSO. BBP enhanced H3K9 acetylation while decreasing H3K9 dimethylation. Fifty μM BBP increased histone acetyltransferases, p300 (P < 0.05) and GCN5 (P < 0.01) gene expression. Furthermore, histone deacetylases (HDACs), HDAC3 (P < 0.01) and HDAC10 (P < 0.01, 10 μM BBP; P < 0.001, 50 μM BBP) and histone methyltransferases, SETDB1 (P < 0.01) and G9a (P < 0.01), were significantly downregulated by BBP exposure. BBP acts, in part, through PPARγ, as PPARγ knockdown led to decreased H3K9ac and rescued H3K9me2 during BBP exposure. In conclusion, BBP regulated MSCs towards adipogenesis by tipping the epigenomic balance.



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Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Marialuisa Sponziello, Francesca Rosignolo, Marilena Celano, Valentina Maggisano, Valeria Pecce, Roberta Francesca De Rose, Giovanni Enrico Lombardo, Cosimo Durante, Sebastiano Filetti, Giuseppe Damante, Diego Russo, Stefania Bulotta
In this study we analyzed the expression levels of markers of epithelial-to-mesenchymal transition (EMT) in several papillary thyroid carcinomas (PTCs) and the relation with tumor genotypes and clinicopathological characteristics. The role of fibronectin-1 (FN1) was investigated by analyzing the effects of FN1 silencing in two human thyroid cancer cell lines.Most of EMT markers were significantly over-expressed in a group of 36 PTCs. In particular, FN1 mRNA levels were higher in tumor vs non-tumor tissue (117.3, p < 0.001) and also in aggressive and BRAF^V600E samples. Similar results were observed (and confirmed at the protein level) when FN1 expression was analyzed in a validation group of 50 PTCs and six lymph node (LN) metastases. Silencing of FN1 in TPC-1 and BCPAP thyroid cancer cells significantly reduced proliferation, adhesion, migration, and invasion in both cell lines.Collectively, our data indicate that FN1 overexpression is an important determinant of thyroid cancer aggressiveness.



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Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): F.P.M. O'Harte, M.T. Ng, A.M. Lynch, J.M. Conlon, P.R. Flatt
The antidiabetic potential of thirteen novel dogfish glucagon derived analogues were assessed in vitro and in acute in vivo studies. Stable peptide analogues enhanced insulin secretion from BRIN-BD11 β-cells (p < 0.001) and reduced acute glycaemic responses following intraperitoneal glucose (25 nmol/kg) in healthy NIH Swiss mice (p < 0.05–p<0.001). The in vitro insulinotropic actions of [S2a]dogfish glucagon, [S2a]dogfish glucagon-exendin-4(31-39) and [S2a]dogfish glucagon-Lys³⁰-γ-glutamyl-PAL, were blocked (p < 0.05–p<0.001) by the specific GLP-1 and glucagon receptor antagonists, exendin-4(9-39) and (desHis¹Pro⁴Glu⁹)glucagon amide but not by (Pro³)GIP, indicating lack of GIP receptor involvement. These analogues dose-dependently stimulated cAMP production in GLP-1 and glucagon (p < 0.05–p<0.001) but not GIP-receptor transfected cells. They improved acute glycaemic and insulinotropic responses in high-fat fed diabetic mice and in wild-type C57BL/6J and GIPR-KO mice (p < 0.05–p<0.001), but not GLP-1R-KO mice, confirming action on GLP-1 but not GIP receptors. Overall, dogfish glucagon analogues have potential for diabetes therapy, exerting beneficial metabolic effects via GLP-1 and glucagon receptors.



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Expression analysis and localization of wt1, ad4bp/sf-1 and gata4 in the testis of catfish, Clarias batrachus: Impact of wt1-esiRNA silencing

Publication date: 15 August 2016
Source:Molecular and Cellular Endocrinology, Volume 431
Author(s): Raju Murugananthkumar, Balasubramanian Senthilkumaran
In teleosts, a comprehensive role or interaction of wt1, ad4bp/sf-1 and gata4 genes in relation to gonadal development and/or recrudescence was never attempted. Present study aimed to identify the involvement of these genes during testicular development of catfish, Clarias batrachus. Dominant expression of wt1 and gata4 was observed in developing and adult testis, while ad4bp/sf-1 showed steady expression. Localization of these genes in adult testis revealed their presence in spermatogonia, spermatocytes and interstitial/Leydig cells. Significant high expression during pre-spawning and spawning phases, and upregulated levels of these genes after hCG induction authenticated gonadotropic regulation. Transient silencing of wt1-esiRNA displayed decrease in wt1 expression, which further downregulated the expression of ad4bp/sf-1 and gata4, and certain steroidogenic enzyme genes related to androgen production. These results suggest that wt1 might target ad4bp/sf-1 and gata4 expression, and also have regulatory influence either indirectly or directly on the steroidogenic enzyme genes of catfish.

Graphical abstract

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Laparoscopy-assisted distal gastrectomy for early gastric cancer poses few limitations for selected elderly patients: a single-center experience

Abstract

Background

The safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer have been demonstrated in clinical studies. The aim of this study was to clarify the safety and efficacy of LADG in patients ≥80 years of age with early gastric cancer, an American Society of Anesthesiologists (ASA) classification of 1–2, and a performance status (PS) of 0–1.

Case presentation

From April 2009 to July 2011, 12 elderly patients aged ≥80 years and 43 younger patients underwent LADG for early gastric cancer. Seven of the 55 patients underwent LADG and simultaneous surgery including surgery for colorectal cancer, cholecystectomy, or other conditions. Forty-eight of the 55 patients who underwent only LADG were studied. Demographics and postoperative outcomes were compared.

Results

The postoperative complication rate, time to first ambulation, time to first flatus, time to first fluid intake, and postoperative hospital stay were similar in these two groups. Nutritional status as assessed by body weight, serum albumin, and total protein at 1 and 3 months after surgery was also similar in these two groups.

Conclusions

Postoperative outcomes were acceptable in the elderly patients included in the study. LADG for early gastric cancer is a safe and effective treatment in elderly patients aged ≥80 years with an ASA status of 1–2 and PS of 0–1.

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Value Based Care and Patient-Centered Care: Divergent or Complementary?

Abstract

Two distinct but overlapping care philosophies have emerged in cancer care: patient-centered care (PCC) and value-based care (VBC). Value in healthcare has been defined as the quality of care (measured typically by healthcare outcomes) modified by cost. In this conception of value, patient-centeredness is one important but not necessarily dominant quality measure. In contrast, PCC includes multiple domains of patient-centeredness and places the patient and family central to all decisions and evaluations of quality. The alignment of PCC and VBC is complicated by several tensions, including a relative lack of patient experience and preference measures, and conceptions of cost that are payer-focused instead of patient-focused. Several strategies may help to align these two philosophies, including the use of patient-reported outcomes in clinical trials and value determinations, and the purposeful integration of patient preference in clinical decisions and guidelines. Innovative models of care, including accountable care organizations and oncology patient-centered medical homes, may also facilitate alignment through improved care coordination and quality-based payment incentives. Ultimately, VBC and PCC will only be aligned if patient-centered outcomes, perspectives, and preferences are explicitly incorporated into the definitions and metrics of quality, cost, and value that will increasingly influence the delivery of cancer care.

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Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21

Abstract

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e⁻⁸) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e⁻¹¹). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus.

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Stable isotope on the evaluation of water quality in the presence of WWTPs in rivers

Abstract

We investigated the distribution of nitrogen compounds in Han River as well as two tributaries of Tancheon and Jungrangcheon. Particularly, we observed the significant releases of NH₄⁺-N from effluent of wastewater treatment plants (WWTPs) in two tributaries that has resulted in the increases of ammonium nitrogen (NH₄⁺-N) in Han River as well as in Tancheon and Jungrangcheon. Due to the increases of NH₄⁺-N in two tributaries, the larger distribution of δ¹⁵N-NH₄⁺ was observed than those of δ¹⁵N-NO₃⁻ in downstream. We calculated the contribution rate of ammonium nitrogen and nitrate nitrogen from effluent to downstream according to the results of stable isotope. The contribution rates of δ¹⁵N-NH₄⁺ from effluent to downstream were significant that ranged between 53 and 100 % in Tancheon and between 27 and 100 % in Jungrangcheon. While the contribution of δ¹⁵N-NO₃⁻ was not significant in Tancheon, it was occasionally observed in Jungrangcheon. These results demonstrated that WWTPs are the major sources of NH₄⁺-N in two tributaries, which caused the distinguishable stable isotope of δ¹⁵N-NH₄⁺. Therefore, the stable isotope of δ¹⁵N-NH₄⁺ could be a useful parameter or tracer for the evaluation of NH₄-N released from WWTPs in rivers.

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Microbial disinfection of water with endotoxin degradation by photocatalysis using Ag@TiO 2 core shell nanoparticles

Abstract

The studies on photocatalytic disinfection of water contaminated with Escherichia coli using Ag core and TiO₂ shell (Ag@TiO₂) nanoparticles under UV irradiation showed that these nanoparticles are very efficient in water disinfection both in their free and immobilised form. Complete disinfection of 40 × 10⁸ CFU/mL could be achieved in 60 min with 0.4 g/L catalyst loading and in 35 min with 1 g/L catalyst loading. Ag@TiO₂ nanoparticles were found to be superior to TiO₂ nanoparticles in photocatalytic disinfection of water. Kinetics of disinfection followed Chick's law, and the pseudo-first-order rate constant was 0.0168 min⁻¹ for a catalyst loading of 0.1 g/L. Disinfection of water and degradation of endotoxins (harmful disinfection residual) occurred simultaneously during photocatalysis thereby making the treated water safe for use. Endotoxin degradation showed a shifting order of kinetics. The rate of photocatalysis with nanoparticles immobilised in cellulose acetate film was marginally lower as compared to that of free nanoparticles. Negligible Ag ion leakage and re-growth of cells post-photo-catalytic treatment of water confirmed that complete disintegration of E. coli occurred during photocatalysis making the treated water safe for use. Therefore, Ag@TiO₂ nanoparticles have a potential for large-scale application in drinking water treatment plants and household purification units.

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An improved biofilter to control the dissolved organic nitrogen concentration during drinking water treatment

Abstract

Dissolved organic nitrogen (DON) is a key precursor of numerous disinfection by-products (DBPs), especially nitrogenous DBPs (N-DBPs) formed during disinfection in drinking water treatment. To effectively control DBPs, reduction of the DON concentration before the disinfection process is critical. Traditional biofilters can increase the DON concentration in the effluent, so an improved biofilter is needed. In this study, an improved biofilter was set up with two-layer columns using activated carbon and quartz sand under different influent patterns. Compared with the single-layer filter, the two-layer biofilter controlled the DON concentration more efficiently. The two-point influent biofilter controlled the DON concentration more effectively than the single-point influent biofilter. The improved biofilter resulted in an environment (including matrix, DO, and pH) suitable for microbial growth. Along the depth of the biofilter column, the environment affected the microbial biomass and microbial activity and thus affected the DON concentration.

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Combination of antibiotics suppressed the increase of a part of ARGs in fecal microorganism of weaned pigs

Abstract

The presence of antibiotic resistance genes (ARGs) is one of the most important public health concerns. Six tetracycline resistance genes (TRGs—tetA, tetC, tetL, tetO, tetW, and tetX) were quantified using real-time quantitative polymerase chain reaction (qPCR) in the fecal microorganisms of weaned pigs. Two hundred 35-day-old weaned pigs were fed different dietary antibiotics for 28 days: (1) no antibiotic as the control treatment (CT); (2) chlortetracycline, bacitracin zinc and colistin sulfate (CBC); (3) bacitracin zinc and colistin sulfate (BC); and (4) chlortetracycline (CTC). The detection frequencies (DFs) of tetC, tetL, and tetW were 100 %; and the DFs of tetA, tetD, tetM, tetO, and tetX were 65 %. The relative abundances (tet/16S rRNA gene copy numbers) of six tet genes (tetA, tetC, tetL, tetO, tetW and tetX) were between 1.5 × 10⁻⁴ and 2.0 × 10⁻¹. In the group CTC, the relative abundances of tetC (P < 0.01), tetL (P < 0.01), tetO (P < 0.05), tetW (P < 0.01), and tetX (P < 0.01) were greater than those of the group CT. Compared with the group CTC, the relative abundances of tetC (P < 0.01), tetL (P < 0.01), and tetW (P < 0.01) were decreased in the CBC and BC groups. These results indicate that a combination of different antibiotics suppressed the abundance increase of a part of tet genes, which suggests that a combination of antibiotics produces multiple selection pressures on fecal microorganism of pigs.

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Cultivating Chlorella vulgaris and Scenedesmus quadricauda microalgae to degrade inorganic compounds and pesticides in water

Abstract

This work evaluates the possibility of cultivating Scenedesmus quadricauda and Chlorella vulgaris microalgae in wastewater from the hydroponic cultivation of tomatoes with the aim of purifying the water. S. quadricauda and C. vulgaris were also used in purification tests carried out on water contaminated by the following active ingredients: metalaxyl, pyrimethanil, fenhexamid, iprodione, and triclopyr. Fifty-six days after the inoculum was placed, a reduction was found in the concentration of nitric nitrogen, ammonia nitrogen, and soluble and total phosphorus. The decrease was 99, 83, 94, and 94 %, respectively, for C. vulgaris and 99, 5, 88, and 89 %, respectively, for S. quadricauda. When the microalgae were present, all the agrochemicals tested were removed more quickly from the water than from the sterile control (BG11). The increase in the rate of degradation was in the order metalaxyl > fenhexamid > iprodione > triclopyr > pyrimethanil. It was demonstrated that there was a real degradation of fenhexamid, metalaxyl, triclopyr, and iprodione, while in the case of pyrimethanil, the active ingredient removed from the substrate was absorbed onto the cells of the microalgae. It was also found that the agrochemicals used in the tests had no significant effect on the growth of the two microalgae. The experiment highlighted the possibility of using cultivations of C. vulgaris and S. quadricauda as purification systems for agricultural wastewater which contains eutrophic inorganic compounds such as nitrates and phosphates and also different types of pesticides.

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Insight into visible light-driven photocatalytic degradation of diesel oil by doped TiO 2 -PS floating composites

Abstract

TiO₂-pearlstone (PS) floatable photocatalysts were synthesized using a facile sol-gel method and confirmed by XRD, N₂ adsorption-desorption, SEM, EDX, TEM, FT-IR, XPS, and UV-vis DRS measurements. It has been found that the photocatalysts composed of anatase TiO₂ deposited on the surface of PS and formed mesoporous structure. By N or B/N doping, the band gap of the photocatalyst has been narrowed. The obtained floatable photocatalysts can be applied to solar light-driven remediation of oil-contaminated water. Diesel oil was chosen as the model pollutant to evaluate the photocatalytic activity. The results showed B/N-TiO₂-PS exhibited the highest photocatalytic activity for diesel oil under visible light irradiation, which is 48 % removal rate for 9 h. The reaction rate constant k of B/N-TiO₂-PS is 0.08423 h⁻¹, which is four times larger than that of pure TiO₂-PS. Moreover, the characteristic of floatable makes the photocatalysts easier to separate and reuse, which showed great potential for practical applications in the field of environmental cleanup and solar energy conversion.

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Impact of molybdenum nanoparticles on survival, activity of enzymes, and chemical elements in Eisenia fetida using test on artificial substrata

Abstract

The influence of molybdenum oxide nanoparticles (MoO₃) on the growth and survival of Eisenia fetida was established. The activity of antioxidant enzymes and changes in concentration of molybdenum in the body of E. fetida were determined. The degree of bacterial bioluminescence inhibition in extracts of substrates and worm was studied using luminescent strain Escherichia coli K12 TG1. The enzymatic activity of substrates before and after exposure with nanoparticles and worms was assessed. Nanoparticles have concentrations of 10, 40, and 500 mg/kg of dry matter, and substrata are made of artificial soil (substrate A) and microcrystalline cellulose (substrate B). Spherical nanoparticles MoO₃, yellow in color, with size 92 ± 0.3 nm, Z-potential 42 ± 0.52 mV, molybdenum content 99.8 mass/%, and specific area 12 m²/g were used in the study. A significant decrease by 23.3 % in weight was registered (for MoO₃ NPs at 500 mg/kg) on substrate A (p ≤ 0.05). On substrate B, the maximum decrease in weight by 20.5, 33.3, and 16.9 % (p ≤ 0.05) was registered at a dose of 10, 40, and 500 mg/kg, respectively; mortality was from 6.6 to 73 %. After the assessment of bacterial bioluminescence inhibition in substrates A and B (extracts) and before worms were put, the toxicity of substrates was established at doses of 40 and 500 mg/kg, expressed in inhibitory concentration (IC) 30 and IC 50 values. Comparatively, on days 7 and 14, after exposure in the presence of E. fetida, no inhibition of bioluminescence was registered in extracts of substrates A and B, indicating the reduction in toxicity of substrates. The initial content of molybdenum in E. fetida was 0.9 ± 0.018 mg/kg of dry matter. The degree of molybdenum accumulation in worm tissue was dependent on the dose and substrate quality. In particular, 2–7 mg/kg of molybdenum accumulated from substrate A, while up to 15 kg/kg of molybdenum accumulated from substrate B (day 7). Molybdenum concentration decreased by 64.8 and 57.4 % at doses 40 and 500 mg/kg, respectively, on day 14. The reaction of antioxidant enzymes was shown in an insignificant increase of glutathione reductase (GSR) and catalase (CAT) at concentrations of 10 and 40 mg/kg in substrate A, followed by the subsequent reduction of their activity at the dose of 500 mg/kg MoO₃. The activity of GSR in substrate B against the presence of MoO₃ nanoparticles decreased, with significant difference of 33.5 % (p ≤ 0.05) at the dose of 500 mg/kg compared with untreated soil. In experiments with substrate A, an increase of catalase activity was registered for the control sample. The presence of MoO₃ nanoparticles at the concentration of 10 mg/kg in the environment promoted enzymatic activity on days 7 and 14, respectively. A further increase of nanoparticle concentration resulted in the decrease of catalase activity with a minimum value at the concentration of MoO₃ of 500 mg/kg. In the experiment with substrate B at the concentration of MoO₃ nanoparticles of 40 mg/kg, enzymatic activity increases on day 7 of exposure. However, the stimulating effect of nanoparticles stops by day 14 of the experiment and further catalase activity is dose dependent with the smallest value in the experiment with MoO₃ having the concentration of 500 mg/kg.

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Bioavailability of pollutants sets risk of exposure to biota and human population in reservoirs from Iguaçu River (Southern Brazil)

Abstract

The Iguaçu River, located at the Southern part of Brazil, has a great socioeconomic and environmental importance due to its high endemic fish fauna and its potential to generate hydroelectric power. However, Iguaçu River suffers intense discharge of pollutants in the origin of the river. In a previous report, the local environmental agency described water quality to improve along the river course. However, no study with integrated evaluation of chemical analysis and biological responses has been reported so far for the Iguaçu River. In the current study, three different Brazilian fish species (Astyanax bifasciatus, Chrenicicla iguassuensis, and Geophagus brasiliensis) were captured in the five cascading reservoirs of Iguaçu River for a multi-biomarker study. Chemical analysis in water, sediment, and muscle indicated high levels of bioavailable metals in all reservoirs. Polycyclic aromatic hydrocarbons (PAHs) were detected in the bile of the three fish species. Integration of the data through a FA/PCA analysis demonstrated the poorest environmental quality of the reservoir farthest from river's source, which is the opposite of what has been reported by the environmental agency. The presence of hazardous chemicals in the five reservoirs of Iguaçu River, their bioaccumulation in the muscle of fish, and the biological responses showed the impacts of human activities to this area and did not confirm a gradient of pollution between the five reservoirs, from the source toward Iguaçu River's mouth. Therefore, diffuse source of pollutants present along the river course are increasing the risk of exposure to biota and human populations.

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Surfactant enhanced pyrene degradation in the rhizosphere of tall fescue ( Festuca arundinacea )

Abstract

The present study was conducted to evaluate the effect of two non ionic surfactants (Tween 80 and Triton X-100), a biosurfactant (Lecithin), and randomly methylated-β-cyclodextrins (RAMEB) on the remediation of pyrene from soil planted with tall fescue (Festuca arundinacea). Soils with pyrene concentration of about 243 mg kg⁻¹ was grown with tall fescue and were individually amended with 0, 200, 600, 1000, and 1500 mg kg⁻¹ of Tween 80, Triton X-100, biosurfactant, and RAMEB. The results show that all surfactants significantly increased plant biomass compared to unamended soil. Dehydrogenase activity was also stimulated as a result of surfactant addition. Only 3.9 and 3.2 % of pyrene was decreased in the uncovered and covered abiotic sterile control, suggesting that microbial degradation was the main removal mechanism of pyrene from soil. In the planted treatment receiving no surfactant, the remediation of pyrene was 45 % which is significantly higher than that of corresponding unplanted control soil, suggesting that the cultivation of tall fescue alone could enhance the overall remediation of pyrene in soil. All surfactants had significantly higher rates of pyrene remediation compared to the unamended planted soil. Generally, RAMEB displayed the highest remediation rates, i.e., 64.4–79.1 % followed by the Triton X-100, i.e., 60.1–74.8 %. The positive impact of surfactants on pyrene remediation could possibly be because of their capacities to increase its bioavailability in soil. The evidence from this study suggests that the addition of surfactants could enhance phytoremediation of PAHs polluted soil.

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Exploitation of subabul stem lignin as a matrix in controlled release agrochemical nanoformulations: a case study with herbicide diuron

Abstract

The utilization of nanomaterials in the domain of agriculture is at an inception, especially in the development of controlled release agrochemical nanoformulations. The present study demonstrated the potential of subabul stem lignin as a matrix material in agrochemical formulations using nanotechnology. In this study, "nanoprecipitation" method was employed and "optimized" to fabricate a stable herbicide, "diuron nanoformulation" (DNF). "Optimized DNF" (ODNF) has 5.17 ± 0.49 % diuron loading efficiency (DLE) and 74.3 ± 4 % encapsulation efficiency (EE). The size of nanoparticles in ODNF was 166 ± 68 nm as revealed by FESEM/TEM studies. Physicochemical characterization of ODNF by UV, FT-IR, and DSC studies revealed the successful loading of diuron within the lignin matrix. The ODNF exhibited nonlinear biphasic release profile for diuron. Further, the bioefficacy of diuron released from ODNF was tested using canola (Brassica rapa). B. rapa seedlings grown in the soil supplemented with ODNF showed early signs of leaf chlorosis and mortality when compared with seedlings grown in the presence of commercial diuron formulation (CDF) or bulk diuron (BD), respectively. This study not only revealed the exploitation of subabul stem lignin as a "matrix" in the controlled release nanoformulation of diuron but also opened up new avenues for utilizing it as matrix for several other agrochemicals associated with the growth and development of the plant.

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Pretreatment quality of life, performance status and their relation to treatment discontinuation and treatment changes in high-risk breast cancer patients receiving chemotherapy: results from the prospective randomized ADEBAR trial

Abstract

Background

Health-related quality of life (QoL) is a self-assessed construct indicating how people feel in regard to aspects of their health. Performance status (PS) is evaluated by the treating physician. We examined whether pretreatment QoL and PS are related to subsequent treatment discontinuation and treatment changes in high-risk breast cancer patients receiving chemotherapy.

Methods

We conducted a prospective cohort study with data from a randomized phase III trial comparing FEC- and EC-DOC-chemotherapy in patients with primary breast cancer (ADEBAR). We examined the patient's request to discontinue the study, discontinuation due to toxicity, the prolongation of therapy, and dose reduction. Baseline QoL was assessed using the EORTC QLQ-C30. PS was evaluated using the Eastern Cooperative Oncology Group Scale (ECOG). Four QoL scales were selected prior to analysis as outcomes: global health, physical functioning, emotional functioning, and fatigue. Multivariate binary logistic regression analyses were used to test for differences within the independent variables.

Main results

1322 patients were included. 1094 (82.8 %) patients completed therapy according to protocol. 6.3 % stopped therapy due to toxicity and 4.4 % refused treatment. Global health was not related to any of the four QoL outcomes. Physical functioning had the strongest impact on QoL, when comparing the fittest group to the lowest quintile [OR 2.14 (95 % CI 1.00–4.60)]. ECOG 0 compared to worse than 1 was strongly correlated to therapy discontinuation due to toxicity [OR 20.15 (95 % CI 9.48–42.83)] and treatment refusal [OR 8.32 (95 % CI 3.81–18.14)].

Conclusions

Pretreatment QoL, especially physical functioning, is associated with subsequent therapy discontinuation due to toxicity and with changes of the treatment protocol. Pretreatment performance status is strongly associated with therapy discontinuation due to toxicity and with treatment refusal.

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Differential role of microRNAs in the pathogenesis and treatment of Esophageal cancer

Publication date: August 2016
Source:Biomedicine & Pharmacotherapy, Volume 82
Author(s): Maryam Hemmatzadeh, Hamed Mohammadi, Mohammad Karimi, Mohammad Hossein Musavishenas, Behzad Baradaran
Esophageal cancer (EC) is the most invasive disease associated with inclusive poor prognosis. EC usually is found as either adenocarcinoma (EAC) or squamous cell carcinomas (ESCC). ESCC forms in squamous cells and highly occurs in the upper third of the esophagus. EAC appears in glandular cells and ordinarily develops in the lower one third of the esophagus near the stomach. Barrett's esophagus (BE) is a metaplastic precursor of EAC. There is a persistent need for improving our understanding of the molecular basis of this disease. MicroRNAs (miRNAs) demonstrate an uncovered class of small, non-coding RNAs that can negatively regulate the protein coding gene, and are associated with approximately all known physiological and pathological processes, especially cancer. MiRNAs can affect cancer pathogenesis, playing a crucial role as either oncogenes or tumor suppressors. The recent emergence of observations on the role of miRNAs in cancer and their functions has induced many investigations to examine their relevance to esophageal cancer. In esophageal cancer, miRNA dysregulation plays a crucial role in cancer prognosis and in patients' responsiveness to neo-adjuvant and adjuvant therapies. In this review, the oncogenic, tumor suppressive, and drug resistance related roles of miRNAs, and their involvement in the pathogenesis and treatment of esophageal cancer were summarized.



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Hypomineralised second primary molars: prevalence, pattern and associated co morbidities in 8- to 10-year-old children in Ile-Ife, Nigeria

Abstract

Background

This study tries to determine the prevalence and co-morbidities associated with hypomineralised second primary molars (HSPM) in 8- to 10- year-old children in Ile-Ife, Nigeria; and the co-existence of HSPM and Molar Incisor Hypomineralisation (MIH) in the study population.

Methods

This was a cross sectional study involving 8- to 10- year-old children in schooling in suburban Nigeria. Information was collected on the child's age, sex and socioeconomic status. Intraoral examination was conducted to determine the presence of HSPM, MIH, caries and the oral hygiene status of study participants. The severity of HSPM was also determined. The prevalence of HSPM, the association between HSPM, sex and socioeconomic status of study participants, the difference in the prevalence of caries and poor oral hygiene in children with and without HSPM, and the prevalence of HSPM and MIH co-morbidity were determined.

Results

Twenty seven of the 469 children examined (5.8 %) had HSPM. The tooth prevalence of HSPM was 3.9 %. There was no significant sex (p = 0.06), age (p = 0.41), and socioeconomic status (p = 0.67) differences between children with HSPM and without HSPM. More children with HSPM had caries (p ≤ 0.001) and poor oral hygiene (p = 0.01). Children with HSPM have increased odds having dental caries (AOR: 6.34; CI: 2.78–14.46; p = <0.001) and reduced odds of having good oral hygiene (AOR: 0.32; CI: 0.13–0.78; p = 0.01) when compare with children without HSPM. Also 77.8 % of children with HSPM also had MIH.

Conclusion

The prevalence of HSPM in the study population is significantly high. The large number of children with HSPM and MIH also suggests that HSPM is a predisposing factor for MIH. The significantly higher proportion of children with HSPM who had caries and poor oral hygiene makes it imperative to institute screening programmes for HSPM/MIH in the study population.

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The Nation and the Family: The Impact of National Identification and Perceived Importance of Family Values on Homophobic Attitudes in Lithuania and Scotland

Abstract

The meanings attached to the nation can be consequential for group members' attitudes and beliefs. We examined how national identity definition can influence the extent of individuals' homophobia with 159 Lithuanian and 176 Scottish university students who completed a questionnaire which measured their national identification, homophobia, and the extent to which they felt traditional family values were central to their nation's identity. Consistent with nation-wide differences in the significance given to the family, Lithuanian participants perceived family values to be more important for their national identity and expressed higher levels of homophobia than did Scottish participants. Moreover, the relationship between level of national identification and homophobia was stronger in Lithuania than in Scotland. Analyses revealed that the perceived importance of family values helped explain the difference between homophobia levels in Lithuania and Scotland. In both sites we found an indirect effect of national identification on homophobia via the perceived importance of family values, but this effect was significantly stronger for Lithuanian participants. These findings illustrate the ways in which identification with the nation is relevant to attitudes concerning sexuality, and how this varies according to national context. Our work indicates that LGBT rights campaigns should be informed by the knowledge that homophobia may be perpetuated by national valorisation of the family.

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