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Introduction and objective. Receiving a cancer diagnosis can lead to significant mental distress, highlighting the necessity for comprehensive medical care that includes psychological support. Effective psycho-oncological therapy can help patients find fulfillment regardless of their prognosis, while also improving overall outcomes and treatment adherence. This article aims to review the medical literature on the mental health challenges faced by cancer patients and to explore potential treatment modalities. Review methods. Implementing Google Scholar and PubMed, a literature analysis was conducted, with particular attention paid to terms like "psychooncology," "anxiety," "depression," "cancer," "grief," and "PTSD." The period of consideration for articles was from 2017 to 2024. Brief description of the state of knowledge. Grief, anxiety, PTSD, despair, and other mental health problems can arise after receiving a cancer diagnosis. In order to improve treatment adherence and survival rates, psychological well-being must be addressed. Empirical evidence indicates that psychological disorders can hinder adherence to therapy and elevate the risk of death from cancer. Furthermore, as families often endure significant stress throughout the disease, psychological care is beneficial to both patients and their relatives. It is possible to enhance adherence and reduce symptoms by using an integrated strategy that takes into consideration both physical and mental health. Conclusions. An essential part of holistic cancer care is psycho-oncology, which enhances patients' general health and quality of life. Psycho-oncological therapy must be incorporated into standard cancer care in order to improve treatment outcomes and assist patients in overcoming their condition.

CRC occupies one of the leading positions among gastrointestinal malignancies and is a significant problem in Europe since it is the third most frequently diagnosed cancer. Recent developments in diagnostic techniques have led to higher chances of early diagnosis and survival; nevertheless, CRC is highly likely to relapse in the survivorably younger individuals. The importance of the current chemotherapy treatment and potential key therapeutic targets are identified in this review so that the molecular alterations causing drug resistance in CRC can be studied.Current literature formed the basis of this review by reviewing the molecular processes that underlie CRC, with emphasis on the mutational alterations in genes such as SENP1, KRAS, APC, TP53, and BRAF that play critical roles in CRC and resistance to treatment. Chemotherapy for CRC, targeting therapies, and immuno therapies have been discussed particularly with reference to their effectiveness for treatment and overcoming resistance.Genomic alterations in some important genes are involved in the onset of CRC and also determined the response to therapies. The KRAS mutations are associated with the resistance to EGFR inhibitors; however, BRAF mutations require BRAF/MEK inhibitors. Lack of MMR system SSR as a trigger for MSI-H status suggests a better response to immunotherapies. In addition, new molecules including SENP1, which involved the DNA repair pathway, and combination using CDK4/6 inhibitors are currently under development to overcome resistance and enhance the patients’ benefits.Colorectal cancer is still a problem, primarily because of its genetic character and high rates of recurrence. Even though chemotherapy and targeted therapies offer helpful results, the problem of resistance stands in the way. Subsequent studies should aim at symptomatic treatment outcomes and combine different drugs in order to enhance long-term treatment outcomes.

Objectives To describe the development, validation and reliability of the Oxford Vaccine Hesitancy Scale (OVHS), a new instrument to assess vaccine hesitancy in the general population.Design Cross-sectional validation study.Setting Internet-based study with participants in the UK and USA.Participants Demographically representative (stratified by age, sex and race) samples from the UK and USA recruited through the Prolific Academic platform.Main outcome measures To demonstrate OVHS development, exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation on the UK sample was performed. Confirmatory factor analysis with a Satorra-Bentler scaled test statistic evaluating goodness of fit statistics including the root mean squared error of approximation (RMSEA), standardised root mean squared residual (SRMR) and comparative fit index (CFI) was performed on the US sample. Reliability as internal consistency was assessed using McDonald’s omega. Evidence in support of the predictive, convergent and discriminant validity of the scale was assessed using logistic regression ORs of association (OR) or Pearson correlation coefficients.Results Data for factor analysis were obtained from 1004 respondents, 504 in the UK and 500 in the USA. A scree plot, minimum average partial correlation analysis and parallel analysis suggested a three-factor 13-item scale with domains of vaccine beliefs (seven items), pain (three items) and personal deliberation (three items). Responses were recorded on a Likert scale ranging from disagree completely to agree completely, with higher score reflecting greater hesitancy. Potential total scores ranged from 13 to 65. Goodness of fit was excellent, with RMSEA=0.044, SRMR=0.041 and CFI=0.977. Predictive validity for COVID-19 vaccination status was excellent, with logistic regression ORs of association (95% CI) of 0.07 (0.04, 0.13), p

Abstract Sarcopenia is a serious systemic disease that reduces overall survival. TAVI is selectively performed in patients with severe aortic stenosis who are not indicated for open cardiac surgery due to severe polymorbidity. Artificial intelligence-assisted body composition assessment from available CT scans appears to be a simple tool to stratify these patients into low and high risk based on future estimates of all-cause mortality. Within our study, the segmentation of preprocedural CT scans at the level of the lumbar third vertebra in patients undergoing TAVI was performed using a neural network (AutoMATiCA). The obtained parameters (area and density of skeletal muscles and intramuscular, visceral, and subcutaneous adipose tissue) were analyzed using Cox univariate and multivariable models for continuous and categorical variables to assess the relation of selected variables with all-cause mortality. 866 patients were included (median(interquartile range)): age 79.7 (74.9–83.3) years; BMI 28.9 (25.9–32.6) kg/m2. Survival analysis was performed on all automatically obtained parameters of muscle and fat density and area. Skeletal muscle index (SMI in cm2/m2), visceral (VAT in HU) and subcutaneous adipose tissue (SAT in HU) density predicted the all-cause mortality in patients after TAVI expressed as hazard ratio (HR) with 95% confidence interval (CI): SMI HR 0.986, 95% CI (0.975–0.996); VAT 1.015 (1.002–1.028) and SAT 1.014 (1.004–1.023), all p

Abstract This study aimed to explore the potential of metal oxides such as Titanate Scrolled Nanosheets (TNs) in improving the radiosensitivity of sarcoma cell lines. Enhancing the response of cancer cells to radiation therapy is crucial, and one promising approach involves utilizing metal oxide nanoparticles. We focused on the impact of exposing two human sarcoma cell lines to both TNs and ionizing radiation (IR). Our research was prompted by previous in vitro toxicity assessments, revealing a correlation between TNs' toxicity and alterations in intracellular calcium homeostasis. A hydrothermal process using titanium dioxide powder in an alkaline solution produced the TNs. Our study quantified the intracellular content of TNs and analyzed their impact on radiation-induced responses. This assessment encompassed PIXE analysis, cell proliferation, and transcriptomic analysis. We observed that sarcoma cells internalized TNs, causing alterations in intracellular calcium homeostasis. We also found that irradiation influence intracellular calcium levels. Transcriptomic analysis revealed marked disparities in the gene expression patterns between the two sarcoma cell lines, suggesting a potential cell-line-dependent nano-sensitization to IR. These results significantly advance our comprehension of the interplay between TNs, IR, and cancer cells, promising potential enhancement of radiation therapy efficiency.

Introduction Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control ‘on-demand’ arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental ‘systematic’ arm, VA-ECMO will be pre-emptively initiated. We hypothesise a ‘systematic’ strategy will increase the number of ventilatory-free days at day 28.Methods and analysis We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.Ethics and dissemination The sponsor is the Assistance Publique–Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.Trial registration number NCT05664204.

Abstract Blastocyst selection is primarily based on morphological scoring systems and morphokinetic data. These methods involve subjective grading and time-consuming techniques. Artificial intelligence allows for objective and quick blastocyst selection. In this study, 608 blastocysts were selected for transfer using morphokinetics and Gardner criteria. Retrospectively, morphometric parameters of blastocyst size, inner cell mass (ICM) size, ICM-to-blastocyst size ratio, and ICM shape were automatically measured by a semantic segmentation neural network model. The model was trained on 1506 videos with 102 videos for validation with no overlap between the ICM and trophectoderm models. Univariable logistic analysis found blastocyst size and ICM-to-blastocyst size ratio to be significantly associated with implantation potential. Multivariable regression analysis, adjusted for woman age, found blastocyst size to be significantly associated with implantation potential. The odds of implantation increased by 1.74 for embryos with a blastocyst size greater than the mean (147 ± 19.1 μm). The performance of the algorithm was represented by an area under the curve of 0.70 (p

Our questionnaire-based study with 14 items proposed an investigation of the dental practitioners' opinions and knowledge of lasers, especially on the diode lasers application in Endodontics. The number of respondents was 104, with a higher percentage of 44.2% between 23-30 years old and 61.5% women. 86.5% of the participants worked in the private dental system. 80.8% of the respondents stated that they do not use the diode laser in their daily practice. Only 43.3% considered diode lasers useful in the sterilization of root canals, and 87.5% of respondents considered the sodium hypochlorite the most effective antiseptic. Among those who do not use laser systems, 76.9% were complaining about the high costs of this equipment. 65.4% of the respondents stated they never used the diode laser during endodontic treatment, and the most frequent use was for sterilizing the infected root canals. 87.5% did not know which wavelength to use in practice. Asked if they would like to learn how to use the laser system, 76.9% (80) of respondents answered affirmatively, and 45.2% of study participants said they wanted to purchase a laser system in the future. There is a great need to educate dentists to use diode lasers and make them aware of their advantages. The only problem at present is the need for more affordable laser equipment.

Objectives To develop and validate the Oxford Needle Experience (ONE) scale, an instrument to assess needle fear, attitudes and expectations in the general population.Design Cross-sectional validation study.Setting Internet-based with participants in the UK and USA.Participants UK and US representative samples stratified by age, sex, and ethnicity using the Prolific Academic platform.Main outcome measures Exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation on the UK sample for the ONE scale. Confirmatory factor analysis (CFA) with a Satorra-Bentler scaled test statistic evaluating the root mean squared error of approximation (RMSEA), standardised root mean squared residual (SRMR) and comparative fit index (CFI) on the US sample. Reliability as internal consistency using McDonald’s omega. Convergent validity using the Pearson correlation coefficient. Predictive and discriminant validity using logistic regression ORs of association (OR).Results The population included 1000 respondents, 500 in the UK and 500 in the USA. Minimum average partial correlation and a scree plot suggested four factors should be retained: injection hesitancy, blood-related hesitancy, recalled negative experiences and perceived benefits, yielding a 19-question scale. On CFA, the RMSEA was 0.070 (90% CI, 0.064 to 0.077), SRMR 0.053 and CFI 0.925. McDonald’s omega was 0.92 and 0.93 in the UK and US samples, respectively. Convergent validity with the four-item Oxford Coronavirus Explanations, Attitudes and Narratives Survey (OCEANS) needle fear scale demonstrated a strong correlation (r=0.83). Predictive validity with a single-question COVID-19 vaccination status question demonstrated a strong association, OR (95% CI) 0.97 (0.96 to 0.98), p

Objective. To understand the sexual and reproductive health (SRH) experiences of migrant women and girls of reproductive age (15–49 years) from the Northern Triangle of Central America (El Salvador, Guatemala and Honduras) during their journey to the United States. Methods. A descriptive, qualitative research design included 39 in-depth interviews with migrant women and unaccompanied migrant girls from El Salvador, Guatemala and Honduras from January to June 2022. Participants were recruited using purposive sampling. Interviews were transcribed, coded and analyzed using thematic analysis. Results. Migrant women and girls lack information and resources to manage their SRH during migration. The SRH of those traveling with smugglers is compromised due to their limited access to menstrual pads, water and sanitation services; the risks of transactional sex and sexual violence; the high risk of sexually transmitted infections; the inability to report sexual violence; the lack of access to SRH and prenatal services; and limited knowledge about their sexual and reproductive rights. Conclusions. There is a significant need for improved interventions during the predeparture phase of migration to inform migrant women and girls about the SRH risks they may encounter and to provide information and resources to support their SRH throughout their journey. Special attention should be directed towards trying to reach girls and women who will travel with smugglers.

Objective. To identify sexual risk behaviors and barriers to sexual and reproductive health care (SRH) among Venezuelan female sex workers living in the Dominican Republic. Methods. This was a mixed-methods study using four focus group discussions (FGDs) and a cross-sectional quantitative survey with Venezuelan migrant female sex workers. The study was conducted from September through October 2021 in two urban areas (Santo Domingo and Puerto Plata) in the Dominican Republic. Information collected from the FGDs was analyzed using thematic content analysis, and quantitative data were analyzed using univariate descriptive statistics. Data analysis was conducted from 30 November 2021 to 20 February 2022. Results. In all, 40 Venezuelan migrant female sex workers with a median (range) age of 33 (19-49) years participated in the FGDs and survey. The FDGs identified barriers to SRH services, including immigration status and its implications for formal employment and health access, mental wellbeing, quality-of-life in the Dominican Republic, navigating sex work, perceptions of sex work, SRH knowledge, and limited social support. Findings of the quantitative analysis indicated that most participants reported feeling depressed (78%), lonely/isolated (75%), and having difficulty sleeping (88%). Participants reported an average of 10 sexual partners in the past 30 days; 55% had engaged in sexual practices while under the influence of alcohol; and only 39% had used a condom when performing oral sex in the past 30 days. Regarding AIDS/HIV, 79% had taken an HIV test in the past 6 months, and 74% knew where to seek HIV services. Conclusions. This mixed-methods study found that nationality and social exclusion have a multilayered influence on migrant female sex workers, sexual risk behaviors, and access to health care. Recommendations for effective evidence-based interventions to address sexual health knowledge need to be implemented to address risky sexual behaviors, improve access to SRH, and reduce affordability barriers.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Background The purpose of this study was to identify latent classes of polysubstance use among adolescents in Jamaica and the role of neighborhood factors in the association with polysubstance use class membership. Methods This secondary analysis utilized a national cross-sectional household drug use survey conducted across 357 households in Jamaica (April 2016–July 2016) among a total of 4,625 individuals. A total of 750 adolescents (11–17 years) were included in this analysis. Latent class analysis (LCA) was conducted to identify polysubstance use patterns as well as latent neighborhood constructs. Neighborhood factors included social disorganization, concentrated disadvantage, community resources, community violence, and police station concentration. Multinomial regression analysis was implemented to evaluate the association between polysubstance use class membership and latent classes of neighborhood factors. Result The prevalence of lifetime polysubstance use was 27.56%. Four classes of polysubstance use were identified by comparing a series of five class models. The Bootstrap Likelihood Ratio Test (BLRT) indicated a good fit for the four-class model (

BackgroundPotentially traumatic experiences and post-migration living difficulties (PMLDs) undoubtedly leave marks on mental health and psychosocial functioning. While PMLDs are recognised as a risk factor for posttraumatic stress disorder and complex posttraumatic stress disorder (described together here as C/PTSD), recent investigations have found that C/PTSD symptoms might also influence the experience of PMLDs. The subjective experience of and coping with PMLDs in the context of C/PTSD symptoms has not yet been explored.MethodsSemi-structured, interpreter-assisted interviews exploring the subjective experience of post-migration living difficulties were conducted with treatment-seeking Afghan refugees and asylum seekers (N = 24) and transcribed verbatim. Participants were screened using the International Trauma Questionnaire (ITQ) and allocated to a C/PTSD group or non-C/PTSD group. We analysed the qualitative interviews using content analysis and then compared the results of the two groups.ResultsOver half of the participants (58.3%) met the criteria for C/PTSD. While the two groups addressed numerous similar themes, the C/PTSD group more frequently mentioned themes associated with C/PTSD symptoms (e.g., intrusions, avoidance, sleep disturbances, affective dysregulation) that influenced their responses to PMLDs. The non-C/PTSD group more often experienced positive emotions such as gratitude and optimism, and showed more active, solution-oriented behaviour as well as positive self-verbalisation.ConclusionTo achieve a deeper understanding of PMLDs, post-traumatic psychopathology should be taken into account, as C/PTSD symptoms influence the experience of and coping with PMLDs. The specifics of individual experiences need to be considered in order to promote adaptive coping with PMLDs and to set individual trauma-focused and transdiagnostic treatment targets. In addition, psychological interventions should incorporate psychoeducation to improve the understanding of the impact of C/PTSD on the current experience of PMLDs.

The beech leaf disease nematode, Litylenchus crenatae subsp. mccannii, is recognized as a newly emergent nematode species that causes beech leaf disease (BLD) in beech trees (Fagus spp.) in North America. Changes of leaf morphology before emergence from the bud induced by BLD can provoke dramatic effects on the leaf architecture and consequently to tree performance and development. The initial symptoms of BLD appear as dark green, interveinal banding patterns of the leaf. Despite the fast progression of this disease, the cellular mechanisms leading to the formation of such aberrant leaf phenotype remains totally unknown. To understand the cellular basis of BLD, we employed several types of microscopy to provide an exhaustive characterization of nematode-infected buds and leaves. Histological sections revealed a dramatic cell change composition of these nematode-infected tissues. Diseased bud scale cells were typically hypertrophied and showed a high variability of size. Moreover, while altered cell division had no influence on leaf organogenesis, induction of cell proliferation on young leaf primordia led to a dramatic change in cell layer architecture. Hyperplasia and hypertrophy of the different leaf cell layers, coupled with an abnormal proliferation of chloroplasts especially in the mesophyll cell layers, resulted in the typical interveinal leaf banding. These discrepancies in leaf cell structure were depicted by an abnormal rate of cellular division of the leaf interveinal areas infected by the nematode, promoting significant increase of cell size and leaf thickness. The formation of symptomatic BLD leaves is therefore orchestrated by distinct cellular processes, to enhance the value of these feeding sites and to improve their nutrition status for the nematode. Our findings thus uncover relevant cellular events and provide a structural framework to understand this important disease.

The paper is devoted to the issue of assessing the range of inclusive teacher competencies by the pedagogical community and their comparative significance for achieving the required learning results by students with disabilities. The paper presents the results of an empirical study aimed at identifying the general and specific in assessing the importance of inclusive competencies of a teacher by various subjects of staffing the inclusive educational process at school. The study involved 983 pedagogical workers employed in mass and correctional schools, as well as in pedagogical universities. They were asked to assess the significance of a set of indicators of the competence of an inclusive teacher, obtained on the basis of an analysis of the texts of 59 approximate basic educational programs for the training of future specialists in the field of inclusion. The results of the study demonstrated that a holistic assessment paradigm has not been formed in the pedagogical community in relation to the inclusive competencies of a teacher, which is expressed in the divergence of the corresponding assessment positions of university teachers who train teachers, teachers of mass and special schools. This confirms the need for further development of the model of inclusive competence of a teacher, its empirical verification and subsequent implementation in educational programs of continuous teacher education in accordance with the rapidly changing conditions of professional activity of teachers in an inclusive school.

Background: In 2019, the World Health Organization identified vaccine hesitancy as a top ten global health threat, which has been exacerbated by the COVID-19 pandemic. Despite local and nationwide public health efforts, adolescent COVID-19 vaccination uptake in the US remains low. This study explored parents’ perceptions of the COVID-19 vaccine and factors influencing hesitancy to inform future outreach and education campaigns. Methods: We conducted two rounds of individual interviews via Zoom in May–September 2021 and January–February 2022, with parents of adolescents from the Greater Newark Area of New Jersey, a densely populated area with historically marginalized groups that had low COVID-19 vaccination uptake. Data collection and analysis was guided by the Increasing Vaccination Model and WHO Vaccine Hesitancy Matrix. Interview transcripts were double-coded and thematically analyzed in NVivo. Results: We interviewed 22 parents (17 in English, 5 in Spanish). Nearly half (45%) were Black and 41% were Hispanic. Over half (54%) were born outside of the US. Most of the parents described that their adolescents had received at least one dose of a COVID-19 vaccine. All but one parent had received the COVID-19 vaccine. Despite strong vaccination acceptance for themselves, parents remained hesitant about vaccinating their adolescents. They were mostly concerned about the safety and potential side effects due to the novelty of the vaccine. Parents sought information about the vaccines online, through healthcare providers and authorities, and at community spaces. Interpersonal communication exposed parents to misinformation, though some personal connections to severe COVID-19 illness motivated vaccination. Historical mistreatment by the healthcare system and politicization of the vaccine contributed to parents’ mixed feelings about the trustworthiness of those involved with developing, promoting, and distributing COVID-19 vaccines. Conclusions: We identified multilevel influences on COVID-19 vaccine-specific hesitancy among a racially/ethnically diverse sample of parents with adolescents that can inform future vaccination interventions. To increase vaccine confidence, future COVID booster campaigns and other vaccination efforts should disseminate information through trusted healthcare providers in clinical and also utilize community settings by addressing specific safety concerns and promoting vaccine effectiveness.

The project aimed to understand the lived experience with inclusive education in the case of a secondary school student with diabetes mellitus type 1 (DM1), his mother and a teacher. Data collected by semi-structured interviews were analyzed by van Manen's thematic analyses of lived experience, whereas three significant themes were identified. Firstly, the quality of communication between school and parents; secondly, the level of empathy, understanding and helpfulness, and thirdly, collaboration between colleagues. Research shows the necessity to expand the education of teachers on the issue of special needs of learners with chronic diseases and extend the educational goals to psychological factors associated with their increased emotional burden. Mutual collaboration of all participants and self-reflection of teachers, supporting good peer relationships and positive school climate is essential.

Abstract Heads-up three-dimensional (3D) surgical visualization systems allow ophthalmic surgeons to replace surgical microscope eyepieces with high-resolution stereoscopic cameras transmitting an image to a screen. We investigated the effectiveness and safety of the heads-up NGENUITY 3D Visualization System in a retrospective evaluation of 241 consecutive vitreoretinal surgeries performed by the same surgeon using conventional microscopy (CM group) over a 1-year period versus the NGENUITY System (3D group) over a consecutive 1-year period. We included for study vitreoretinal surgeries for treatment of retinal detachment (RD) (98 surgeries), macular hole (MH) (48 surgeries), or epiretinal membrane (ERM) (95 surgeries). A total of 138 and 103 eyes were divided into 3D and CM groups, respectively. We found no differences in 3-month postoperative rates of recurrence of RD (10% versus 18%, p = 0.42), MH closure (82% versus 88%, p = 0.69), or decrease in central macular thickness of ERMs (134 ± 188 µm versus 115 ± 105 µm, p = 0.57) between the 3D and CM groups, respectively. Surgery durations and visual prognosis were also similar between both groups. We consolidate that the NGENUITY System is comparable in terms of visual and anatomical outcomes, giving it perspectives for integration into future robotized intervention.

Introduction HIV continues to have great impact on millions of lives. Novel methods are needed to disrupt HIV transmission networks. In the USA, public health departments routinely conduct contact tracing and partner services and interview newly HIV-diagnosed index cases to obtain information on social networks and guide prevention interventions. Sequence clustering methods able to infer HIV networks have been used to investigate and halt outbreaks. Incorporation of such methods into routine, not only outbreak-driven, contact tracing and partner services holds promise for further disruption of HIV transmissions.Methods and analysis Building on a strong academic–public health collaboration in Rhode Island, we designed and have implemented a state-wide prospective study to evaluate an intervention that incorporates real-time HIV molecular clustering information with routine contact tracing and partner services. We present the rationale and study design of our approach to integrate sequence clustering methods into routine public health interventions as well as related important ethical considerations. This prospective study addresses key questions about the benefit of incorporating a clustering analysis triggered intervention into the routine workflow of public health departments, going beyond outbreak-only circumstances. By developing an intervention triggered by, and incorporating information from, viral sequence clustering analysis, and evaluating it with a novel design that avoids randomisation while allowing for methods comparison, we are confident that this study will inform how viral sequence clustering analysis can be routinely integrated into public health to support the ending of the HIV pandemic in the USA and beyond.Ethics and dissemination The study was approved by both the Lifespan and Rhode Island Department of Health Human Subjects Research Institutional Review Boards and study results will be published in peer-reviewed journals.

Objectives To develop and validate the Oxford Pandemic Attitude Scale-COVID-19 (OPAS-C), a multidimensional scale that addresses seven domains over 20 items including stress, fear, loneliness, sense of community, belief that the pandemic is a hoax or exaggerated, the use of and attitude to non-pharmaceutical interventions and vaccine hesitancy, in a single measure.Design Cross-sectional validation study.Setting Internet based with respondents in the USA and UK.Participants General community respondents using the Prolific Academic platform.Main outcome measures Exploratory factor analyses with promax oblique rotation and confirmatory factor analysis including goodness of fit indices: root mean square error of approximation (RMSEA), standardised root mean square residual (SRMR) and comparative fit index (CFI). Reliability as internal consistency using Cronbach’s alpha. Convergent and discriminant validity using Pearson correlation coefficients.Results The sample included 351 respondents in the USA and the factorial structure was confirmed using a separate set of 348 respondents in the UK. The OPAS-C had excellent goodness of fit characteristics, with an RMSEA of 0.047 (90% CI 0.037 to 0.056), SRMR of 0.043 and CFI of 0.962. Reliability was excellent, demonstrating Cronbach’s alpha of 0.87 in both the US and UK samples. Convergent validity showed correlation coefficients of 0.54 and 0.49 in the US and UK samples, respectively. Discriminant validity demonstrated correlations of 0.21 and 0.26 in the US and UK samples, respectively.Conclusions The OPAS-C represents the first validated scale that addresses mental health measures and public health-relevant responses to COVID-19, and may be a useful measure for use in future longitudinal and cross-sectional studies. Further international validation beyond the USA and UK may be helpful.

Dento-maxilares anomalies can cause severe three-dimensional disorders of the dental arches and implicitly of dental occlusion, interfering with the harmonious development of the physiological dentition, so is necessary to treat the anomalies as soon is possible. The earlier the age of intervention, the higher the success of an orthodontic treatment, having the possibility of guiding the remaining growth, of controlling the dental eruption and permutation, of correcting bad habits by remouvable or fixed appliances. Aim. The authors have done an evaluation of the oral hygiene practices of patients undergoing mobile orthodontic therapy and the impact on their diet and lifestyle in general. Material and method. A questionnaire with 14 questions has been distributed to a number of 63 patients undergoing the active stage of the orthodontic treatment with mobile appliances at the school medical centre in Bucharest, School no. 5. Children aged up to 10 years old have been helped by their parents to fill out this survey, and older children filled out the survey on their own. Results. Most of the respondents have understood the importance of the dental appliance hygiene and teeth hygiene, and then almost in equal shares they have understood also, the importance of diet and of auxiliary means of hygiene. Majority of children (high percentage of the patients 80% ),have indicated that the orthodontic treatment will benefit them an improved esthetic aspect and healthy teeth. They also noticed the importance of the dental appliance hygiene and teeth hygiene, and then have understood , the importance of diet and of auxiliary means of hygiene (89%). Conclusion. There is an obvious tendency of increased desire for an orthodontic therapy within the analyzed population, most of the patients being aware of the role and need to wear an orthodontic appliance.

Exosomes, belonging to the group of extracellular bodies, are released by healthy as well as cancerous cells and serve as a communication pathway. Tumor-derived exosomes (TEX) possess the capacity to reprogram the function of normal cells owing to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment to promote angiogenesis. Blood supply is essential in solid tumor growth and metastasis. The potential of pro-angiogenic changes is enhanced by an increased amount of circulating tumor-derived exosomes in the body fluids of cancer patients. A vascular network is important, since the proliferation, as well as the metastatic spread of cancer cells depends on an adequate supply of oxygen and nutrients, and the removal of waste products. New blood vessels and lymphatic vessels are formed through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. Thousands of patients have received anti-angiogenic therapy to date. Despite their theoretical efficacy, anti-angiogenic treatments have not proved beneficial in terms of long-term survival. Tumor-derived exosomes carrying pro-angiogenic factors might be a target for new anti-cancer therapy.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

The study of therapeutic uses of musical improvisation can help to improve music therapy assessment which is the aim of this paper. This paper identifies 1. the individual challenges and strengths that may help to deal with problems reflected in musical improvisations of children with special needs and, 2. ways of their identification while listening to the children’s musical expression. Data collected from 180 verbal descriptions of musical improvisations of four children with special needs and then analysed using grounded theory as well as content analysis of documents. It was found that music reflects children’s problems (with mainly bio-behavioural character) as well as their strengths that may be helpful in coping with those problems. Some theoretical guidelines for analysis of musical improvisation and the planning of music therapy intervention were suggested based on these findings.

Background: Vibroacoustic therapy (VAT) uses low-frequency sound, often combined with listening to music, for therapeutic purposes. However, the impact of low-frequency vibration (LFV) on physiological functions and subjective perception is relatively unknown. Methods: We conducted a randomized cross-over study with the aim of comparing the effect of constant LFV of 40 Hz, its amplitude modulation, and the placebo condition on heart rate variability (HRV), stress perception (measured by visual analogue scales for stress) and mood (measured by UWIST Mood Adjective Check List). Results: Research experiments with various interventions (constant LFV with sound of nature (river in forest), amplitude modulation of the same LFV with sounds of nature and sounds of nature without LFV) were realised involving 24 participants. It was found there was an effect on HRV, stress perception and mood after the interventions. However, there were only seldomly experienced, and mostly nonsignificant, differences between the intervention conditions, so the effects may be attributed to factors other than LFV. Conclusions: Large scale experimental studies are needed to verify the preliminary findings and to explore various coinciding factors that may have influenced the results of this study, e.g., type of autonomic nervous system. We propose that the effect of LFV exposure may differ when combined with listening to music, and this hypothesis should be investigated in future studies.

Clinical and surveillance testing for the SARS-CoV-2 virus relies overwhelmingly on RT-qPCR-based diagnostics, yet several popular assays require 2–3 separate reactions or rely on detection of a single viral target, which adds significant time, cost, and risk of false-negative results. Furthermore, multiplexed RT-qPCR tests that detect at least two SARS-CoV-2 genes in a single reaction are typically not affordable for large scale clinical surveillance or adaptable to multiple PCR machines and plate layouts. We developed a RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (LuNER) to address these shortcomings and meet the testing demands of a university campus and the local community. This cost-effective test is compatible with BioRad or Applied Biosystems qPCR machines, in 96 and 384-well formats, with or without sample pooling, and has a detection sensitivity suitable for both clinical reporting and wastewater surveillance efforts.

Over the last decade, Egypt's aquaculture sector has expanded rapidly, which has contributed substantially to per capita fish supply, and the growth of domestic fish markets and employment across the aquaculture value chain. Despite the growing importance of aquaculture sector in Egyptian labour force, only a few studies have explored the livelihoods of Egypt's women and men fish retailers. Even fewer studies have examined gender-based market constraints experienced by these informal fish retailers. This study uses sex-disaggregated data collected in 2013 in three governorates of Lower Egypt to examine the economic and social constraints to scale of enterprises between women (n = 162) and men informal fish retailers (n = 183). Specifically, we employ linear regression method to determine the correlates of enterprise performance. We found that both women and men retailers in the informal fish market earn low profits and face livelihood insecurities. However, women's enterprise performance is significantly lower than that of men even after controlling for individual socio-economic and retailing characteristics. Specifically, the burden of unpaid household work and lack of support therein impedes women's ability to generate higher revenues. These findings strengthen the argument for investing in understanding how gender norms and attitudes affect livelihood options and outcomes. This leads to recommendations on gender-responsive interventions that engage with both men and women and enhance the bargaining power and collective voice of fish retailers.

IntroductionAt low mutation-detection thresholds, next generation sequencing (NGS) for HIV-1 genotypic resistance testing is susceptible to artifactual detection of mutations arising from PCR error and APOBEC-mediated G-to-A hypermutation.MethodsWe analyzed published HIV-1 pol Illumina NGS data to characterize the distribution of mutations at eight NGS mutation detection thresholds: 20%, 10%, 5%, 2%, 1%, 0.5%, 0.2%, and 0.1%. At each threshold, we determined proportions of amino acid mutations that were unusual (defined as having a prevalence ResultsEight studies, containing 855 samples, in the NCBI Sequence Read Archive were analyzed. As detection thresholds were lowered, there was a progressive increase in the proportion of positions with usual and unusual mutations and in the proportion of all mutations that were unusual. The median proportion of positions with an unusual mutation increased gradually from 0% at the 20% threshold to 0.3% at the 1% threshold and then exponentially to 1.3% (0.5% threshold), 6.9% (0.2% threshold), and 23.2% (0.1% threshold). In two of three studies with available plasma HIV-1 RNA levels, the proportion of positions with unusual mutations was negatively associated with virus levels. Although the complete set of signature APOBEC mutations was much smaller than that of unusual mutations, the former outnumbered the latter in one-sixth of samples at the 0.5%, 1%, and 2% thresholds.ConclusionsThe marked increase in the proportion of positions with unusual mutations at thresholds below 1% and in samples with lower virus loads suggests that, at low thresholds, many unusual mutations are artifactual, reflecting PCR error or G-to-A hypermutation. Profiling the numbers of unusual and signature APOBEC pol mutations at different NGS mutation detection thresholds may be useful to avoid selecting a threshold that is too low and poses an unacceptable risk of identifying artifactual mutations.

Aims: This prospective study aimed to evaluate the relationship between persistently elevated lactate values in the arterial blood of newborns with grade II and III hypoxic ischemic encephalopathy (treated with therapeutic hypothermia) and psychomotor development at 24 months. Methods: 51 neonates of gestational age from 36 to 41 weeks receiving therapeutic hypothermia for moderate to severe hypoxic ischaemic encephalopathy had arterial blood lactate levels regularly analysed. At 24 months the infants' psychomotor development was evaluated and they were divided into two groups - those where the outcome was favourable (i.e. normal psychomotor development) and adverse (severe motor or sensory impairment or death). The lactate dynamics over time were retrospectively evaluated from the data collected, with the normal upper limit set at 4 mmol/L. Results: Of the 51 affected neonates, 7 died over the course of the study. 34 of the remaining 44 infants demonstrated normal psychomotor findings at 2 years old, with adverse findings in 10 cases. Although both groups experienced significant reductions in lactate over time, there were statistically significant differences between them regarding currently measured lactate levels. Conclusion: Absolute lactate values and their development over time can be a used as an auxiliary factor in making early estimates of the long-term outcome for newborns with neonatal asphyxia being treated with therapeutic hypothermia.

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

Understanding the causes of genetic variation in real populations has been elusive. Competing theories claim that neutral vs. selective processes have a greater influence on the genetic variation within a population. A key difference among theories is the relationship between population size and genetic diversity. Our study tests this empirically by sampling two species of herbivorous lizards (Dipsosaurus dorsalis and Sauromalus ater) and two species of carnivorous lizards (Crotaphytus bicinctores and Gambelia wislizenii) that vary in population size at the same locality, and comparing metrics of genetic diversity. Contrary to neutral expectations, results from four independent loci showed levels of diversity were usually higher for species with smaller population sizes. This suggests that selective processes may be having an important impact on intraspecific diversity in this reptile community, although tests showed little evidence for selection on the loci sequenced for this study. It is also possible that idiosyncratic histories of the focal species may be overriding predictions from simple neutral models. If future studies show that lack of correlation between population size and genetic diversity is common, methods using genetic diversity to estimate population parameters like population size or time to common ancestor should be used with caution, as these estimates are based on neutral theory predictions.

The purpose of the study was to examine the role of objective and subjective measures of neighborhood crime and disorder on substance use among a nationally representative sample of 4525 Jamaicans aged 12-65 years. Log-Poisson models with generalized estimating equations were used to estimate relative risks (RR) and 95% confidence intervals (CI). A test of interaction was used to determine presence of effect modification by sex. Approximately 39% of the study population reported past-month alcohol use; 10% past-month tobacco use; and 15% past-month marijuana use. In fully adjusted models, past-month alcohol and tobacco use were associated with perceived neighborhood disorder (p

Aims: The objectives of this pilot study were to assess the potential use of 3D videography for analyzing the motion of the body center of mass (COM) in newborns and to determine differences in spontaneous movements between preterm and full-term infants. Methods: The group comprised 10 preterm newborns (gestational age at birth between 26 and 37 weeks; birth weight 800 to 2960 g; gestational age at the time of examination 34 to 39 weeks) and 10 full-term infants (gestational week 38 to 41; birth weight 2810 to 4360 g). To determine the range of motion of the COM, 3D videography was used (2 cameras, 25 Hz). When recording their movements, the infants were in the supine position, calm and awake. The recordings were processed using the APAS software. Selected points on the body were marked to obtain data for calculating the basic parameters of COM trajectories. Results: The range of motion of the COM in both craniocaudal and anteroposterior directions was significantly greater in premature infants (P < 0.05 and P < 0.01, respectively) than in full-term babies. The variability of motion of the COM was significantly greater in the craniocaudal (P < 0.01) and anteroposterior (P < 0.05) directions in preterm babies. This was also valid for the velocity of motion of the COM in the craniocaudal direction (P < 0.05). Conclusions: 3D videography can be used for experimental assessment of motor behavior in preterm infants. Basic kinematic characteristics of the motion of the COM (range, variability, velocity) are greater in preterm infants.

The genus Clea from SE Asia is from one of only two unrelated families among the megadiverse predatory marine Neogastropoda to have successfully conquered continental waters. While little is known about their anatomy, life history and ecology, interest has grown exponentially in recent years owing to their increasing popularity as aquarium pets. However, the systematic affinities of the genus and the validity of the included species have not been robustly explored. Differences in shell, operculum and radula characters support separation of Clea as presently defined into two distinct genera: Clea, for the type species Clea nigricans and its allies, and Anentome for Clea helena and allies. A five-gene mitochondrial (COI, 16S, 12S) and nuclear (H3, 28S) gene dataset confirms the placement of Anentome as a somewhat isolated offshoot of the family Nassariidae and sister to the estuarine Nassodonta. Anatomical data corroborate this grouping and, in conjunction with their phylogenetic placement, support their recognition as a new subfamily, the Anentominae. The assassin snail Anentome helena, a popular import through the aquarium trade so named for their voracious appetite for other snails, is found to comprise a complex of at least four species. None of these likely represents true Anentome helena described from Java, including a specimen purchased through the aquarium trade under this name in the US and one that was recently found introduced in Singapore, both of which were supported as conspecific with a species from Thailand. The introduction of Anentome “helena” through the aquarium trade constitutes a significant threat to native aquatic snail faunas which are often already highly imperiled. Comprehensive systematic revision of this previously unrecognized species complex is urgently needed to facilitate communication and manage this emerging threat.

INTRODUCTION: South Africa (SA) implemented the Global Youth Tobacco Survey (GYTS) four times between 1999 and 2011. Data from the four surveys indicated that downward trends in cigarette use among students may have stalled. Understanding the effect of school anti-smoking education on current smoking among students within schools and variability across schools may provide important insights into policies aimed at preventing or reducing tobacco use among students. Objective were to assess the student- and school-level effects of students exposure to school anti-smoking education on current cigarette use among the study population using the most recent wave of GYTS data in SA (2011). METHODS: an analytic sample of students 13-15 years of age was selected (n=3,068) from the SA GYTS 2011. A taxonomy of two-level logistic regression models was fit to assess the relationship of various tobacco use, control, and exposure predictor variables on current cigarette smoking among the study population. RESULTS: at the student-level in the full model, secondhand smoke (SHS) exposure, peer smoking, and ownership of a promotional item were significantly associated with higher risk of current smoking. At the school-level in the full model, average exposure to peer smoking was associated with significant increases in the prevalence of current cigarette use, while average family anti-smoking education was significantly associated with decreases in the outcome variable. School anti-smoking education was not a statistically significant predictor at the student- or school-levels. CONCLUSION: in this study, exposure to school anti-smoking education had no association with current cigarette smoking among the study population. Consistent with previous studies, having peers that smoked was highly associated with a student being a current smoker. Interestingly, at the school-level in the multilevel analysis, schools with higher rates of average family anti-smoking education had lower prevalence of current smoking. This finding has potential implications for tobacco control in SA, particularly if the school-level, family-centered protective effect can be operationalized as a prevention tool in the country�s tobacco control program.

More than 93 percent of parents place high importance on sex education in both middle and high school. Sex education in middle and high school is widely supported by parents regardless of their political affiliation. Using data from a large diverse sample of 1,633 parents of children aged 9 to 21 years, we examined whether views on sex education differed by parents' political affiliation. More than 89 percent of parents that identified as Republicans or Democrats support including a wide range of topics in sex education including puberty, healthy relationships, abstinence, sexually transmitted diseases (STDs) and birth control in high school. In middle school, 78 percent or more of both parents that identified as Republicans and Democrats support the inclusion of those topics. Controlling for key demographic factors, parents that identified as Democrats are more likely than those that identified as Republicans to support the inclusion of the topics of healthy relationships, birth control, STDs, and sexual orientation in both middle and high school. However, a strong majority of Republican parents want all these topics included in sex education. Sex education which includes a broad set of topics represents an area of strong agreement between parents of both political parties.

La presente revisión de tema ojo seco está orientada a médicos no oftalmólogos. Se realiza un repaso de la anatomía del sistema lagrimal y fisiología básica de la película lagrimal. Se define el concepto de ojo seco, su importancia epidemiológica y su sintomatología. Se realiza un detallado análisis de la clasificación etiológica definiendo las diferencias entre hipolacrimea asociada o no a síndrome de Sjögren y ojo seco evaporativo de causa intrínseca y extríniseca, con énfasis en los mecanismos fisiopatológicos subyacentes. Se entrega una visión que da cuenta de la complejidad, envergadura y condición multifactorial de este problema de salud visual y se hace énfasis en la necesidad de identificar de manera integral el tipo de ojo seco para poder instalar un tratamiento basado en la corrección del mecanismo subyacente y no a través de aproximación sintomática de la terapia.

A splicing mutation in the IKBKAP gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we found new molecular insights for the IKAP role and the impact of the FD mutation in the human PNS lineage by using a novel and unique human embryonic stem cell (hESC) line homozygous to the FD mutation originated by pre implantation genetic diagnosis (PGD) analysis. We found that IKBKAP downregulation during PNS differentiation affects normal migration in FD-hESC derived neural crest cells (NCC) while at later stages the PNS neurons show reduced intracellular colocalization between vesicular proteins and IKAP. Comparative wide transcriptome analysis of FD and WT hESC-derived neurons together with the analysis of human brains from FD and WT 12 weeks old embryos and experimental validation of the results confirmed that synaptic vesicular and neuronal transport genes are directly or indirectly affected by IKBKAP downregulation in FD neurons. Moreover we show that kinetin (a drug that corrects IKBKAP alternative splicing) promotes the recovery of IKAP expression and these IKAP functional associated genes identified in the study. Altogether, these results support the view that IKAP might be a vesicular like protein that might be involved in neuronal transport in hESC derived PNS neurons. This function seems to be mostly affected in FD-hESC derived PNS neurons probably reflecting some PNS neuronal dysfunction observed in FD.

Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans.We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin.Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo.Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.ClinicalTrials.gov NCT01682694.

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p

Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study.Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥ 13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥ 2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments.Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% 'untreated' (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P

BackgroundPseudobulbar affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA.MethodsParticipating clinicians were asked to enroll ≥20 consenting patients with any of 6 conditions: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study-Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient's quality of life (QOL). Presence of PBA symptoms was defined as a CNS-LS score ≥13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded.ResultsPRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score ≥13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS ≥13 vs ConclusionsData from PRISM, the largest clinic-based study to assess PBA symptom prevalence, showed that PBA symptoms were common among patients with diverse neurological conditions. Higher CNS-LS scores were associated with impaired QOL and greater use of antipsychotic/antidepressant medications. These data underscore a need for greater awareness, recognition, and diagnosis of PBA.

Chronic inflammation, which is associated with obesity, may play a role in the etiology of several diseases. Thus, reducing inflammation may offer a disease-prevention strategy, particularly among the obese. Several modifiable factors have been associated with inflammation, including: dietary fiber intake, saturated fat intake, physical activity, smoking, alcohol, and use of certain supplements and medications (glucosamine, chondroitin, fish oil, vitamin E, statins and aspirin). To study whether these associations differ by body mass index (BMI), we used data on 9,895 adults included in the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression was used to evaluate the associations between modifiable factors and serum high-sensitivity C-reactive protein (hsCRP) concentrations across the following groups: underweight/normal weight (BMI

Psoriasis is characterized by hyperplasia of the epidermis and infiltration of leukocytes into both the dermis and epidermis. IL-23, a key cytokine that induces T(H)17 cells, has been found to play a critical role in the pathogenesis of psoriasis. Apilimod is a small-molecule compound that selectively suppresses synthesis of IL-12 and IL-23. An open-label clinical study of oral administration of apilimod was conducted in patients with psoriasis. Substantial improvements in histology and clinical measurements were observed in patients receiving 70 mg QD. The expression of IL-23p19 and IL-12/IL-23p40 in skin lesions was significantly reduced in this dose group, with a simultaneous increase in IL-10 observed. A decrease in the levels of T(H)1 and T(H)17 cytokines/chemokines in skin lesions followed these p19 and p40 changes. In parallel, a reduction in skin-infiltrating CD11c(+) dendritic cells and CD3(+) T cells was seen, with a greater decrease in the CD11c(+) population. This was accompanied by increases in T and B cells, and decreases in neutrophils and eosinophils in the periphery. This study demonstrates the immunomodulatory activity of apilimod and provides clinical evidence supporting the inhibition of IL-12/IL-23 synthesis for the treatment of T(H)1- and T(H)17-mediated inflammatory diseases.

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p