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Pathogens (Basel, Switzerland) Jan 2022In this article, we highlight technological pediatric TB research advances across the TB care cascade; discuss recently completed or ongoing work in adults and...
In this article, we highlight technological pediatric TB research advances across the TB care cascade; discuss recently completed or ongoing work in adults and corresponding significant research gaps for children; and offer recommendations and opportunities to increase investments and accelerate pediatric TB R&D.
PubMed: 35215073
DOI: 10.3390/pathogens11020128 -
Pharmacological Research Jul 2021Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular... (Review)
Review
Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is an apoB100 containing lipoprotein covalently bound to apolipoprotein(a) [apo(a)], a glycoprotein. Plasma Lp(a) levels are to a large extent determined by genetics. Its link to cardiovascular disease (CVD) may be driven by its pro-inflammatory effects, of which its association with oxidized phospholipids (oxPL) bound to Lp(a) is the most studied. Various inflammatory conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus, acquired immunodeficiency syndrome, and chronic renal failure are associated with high Lp(a) levels. In cases of RA, high Lp(a) levels are reversed by interleukin-6 receptor (IL-6R) blockade by tocilizumab, suggesting a potential role for IL-6 in regulating Lp(a) plasma levels. Elevated levels of IL-6 and IL-6R polymorphisms are associated with CVD. Therapies aimed at lowering apo(a) and thereby reducing plasma Lp(a) levels are in clinical trials. Their results will determine if reductions in apo(a) and Lp(a) decrease cardiovascular outcomes. As we enter this new arena of available treatments, there is a need to improve our understanding of mechanisms. This review will focus on the role of Lp(a) in inflammation and CVD.
Topics: Animals; Cardiovascular Diseases; Humans; Inflammation; Lipoprotein(a)
PubMed: 34033878
DOI: 10.1016/j.phrs.2021.105689 -
The American Journal of Clinical... Oct 2023Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference... (Observational Study)
Observational Study
BACKGROUND
Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile.
OBJECTIVES
This study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS).
METHODS
This is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5-19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score.
RESULTS
We obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and-2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian -0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black -0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score.
CONCLUSIONS
These reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.
Topics: Adolescent; Humans; Female; Child; United States; Male; Absorptiometry, Photon; Bone Density; Nutrition Surveys; Reference Values; Prospective Studies; Body Composition; Obesity; Body Mass Index
PubMed: 37598746
DOI: 10.1016/j.ajcnut.2023.08.006 -
Antiviral Therapy Apr 2022The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and... (Review)
Review
The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or more small molecule drugs. This review aims to highlight the discovery, development, and impact of one such molecule, namely, emtricitabine (FTC, emtriva), which is one of the most successful drugs in the fight against HIV/AIDS and has been taken by over 94% of individuals infected with HIV in the USA. We also pay tribute to Dr. John C. Martin, former CEO and Chairman of Gilead Sciences, who unexpectedly passed away in 2021. A true visionary, he was instrumental in delivering FTC, as part of combination therapy with TDF (tenofovir, viread) to the global stage. As the fight to eradicate HIV marches on, we honor Dr. Martin's legacy of collaboration, achievement, and hope.
Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Humans; Male; Tenofovir
PubMed: 35491570
DOI: 10.1177/13596535211067599 -
Journal of Fungi (Basel, Switzerland) Jun 2021The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior... (Review)
Review
The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, several cases of histoplasmosis were documented both in the pediatric and adult populations. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939-2021). North America ( = 1231) had the highest number of cases, followed by South America ( = 135), Africa (n = 65), Asia ( = 26) and Europe ( = 4). Histoplasmosis was much more common in the non-HIV pediatric population ( = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies ( = 207), such as leukemias and lymphomas as well as their treatment, lung diseases ( = 7), environmental exposures and toxins ( = 224), autoimmune diseases ( = 12), organ transplants ( = 12), long-term steroid therapy ( = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors ( = 7) malnutrition ( = 12), histiocytosis ( = 3), Hyper immunoglobulin M and E syndromes ( = 15, 1.2%), pancytopenia ( = 26), diabetes mellitus ( = 1) and T-cell deficiency ( = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions.
PubMed: 34209280
DOI: 10.3390/jof7070530 -
Health Expectations : An International... Jun 2022Better transparency of research results and participant engagement may help address poor participant accrual in paediatric clinical research. We conducted formative... (Review)
Review
INTRODUCTION
Better transparency of research results and participant engagement may help address poor participant accrual in paediatric clinical research. We conducted formative research to assess the acceptability of lay summaries and thank you notes, as well as to refine and expand guidance on participant and family engagement in Pediatric Trials Network's (PTN) pragmatic paediatric clinical research.
METHODS
Informed by draft PTN guidance, we conducted in-depth qualitative interviews with adolescent clinical trial participants and caregivers of paediatric participants in four trials conducted by PTN across eight sites. Participants were shown multiple versions of mock lay summaries and thank you notes and asked questions on their preferences for content and layout, and on trial communications. We used applied thematic analysis to analyse the data.
RESULTS
We interviewed 27 individuals engaged in PTN research: 24 caregivers and 3 adolescents. During a trial, participants want regular updates on study progress, reminders of the study purpose and reassurances of data confidentiality. After the trial, participants want to learn the aggregated results, particularly medication effectiveness. Participants reported that lay summaries should include a review of the study's purpose, methods and length, and that they expect to learn individual-level results. Participants stated that thank you notes must be of sufficient length to be meaningful.
CONCLUSIONS
This is the first study to describe stakeholder preferences for thank you note content and layout. Using these findings, we finalized PTN's trial communication guidance for use in future PTN trials. Research is needed to determine the effect of lay summaries and thank you notes on improving public transparency regarding clinical trials and paediatric trial recruitment and completion.
PATIENT OR PUBLIC CONTRIBUTION
By design, stakeholders (adolescent trial participants and caregivers of pediatric trial participants) contributed to PTN's guidance on the content and layout of lay summaries and thank you notes through their participation in the in-depth interviews.
Topics: Adolescent; Caregivers; Communication; Humans; Pragmatic Clinical Trials as Topic
PubMed: 35246906
DOI: 10.1111/hex.13448 -
Journal of Preventive Medicine and... Sep 2020HIV/AIDS remains a major public health concern globally and Health Care Workers (HCWs) are in the frontline of preventing and providing care in the health care system....
BACKGROUND
HIV/AIDS remains a major public health concern globally and Health Care Workers (HCWs) are in the frontline of preventing and providing care in the health care system. The aim of this study was to evaluate HIV/AIDS knowledge among Iranian HCWs.
METHODOLOGY
This cross-sectional study was conducted among 200 HCWs who were randomly selected from health care centers in Kermanshah city, west of Iran, 2018. HCWs filled out a self-administered questionnaire including the socio-demographic characteristics and HIV/AIDS knowledge items. Data were analyzed by SPSS version 16 using bivariate correlations, t-test, and ANOVA statistical tests.
RESULTS
The mean score of HIV/AIDS knowledge was 29.73 [95% CI: 28.79, 30.67], ranged from 0 to 40 (74.3% of total percent). There was no significant association and correlation between HIV/AIDS knowledge and sex, education level, marital status, age and job history. Up to 50% had inadequate knowledge about HIV/AIDS status and transmission in Iran.
CONCLUSIONS
HCWs HIV/AIDS knowledge was average and it seems need to be educating regarding HIV/AIDS status and transmission in Iran.
Topics: Acquired Immunodeficiency Syndrome; Adult; Cross-Sectional Studies; Female; HIV Infections; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Iran; Male; Middle Aged; Surveys and Questionnaires; Young Adult
PubMed: 33150227
DOI: 10.15167/2421-4248/jpmh2020.61.3.1474 -
Journal of Infection in Developing... Jul 2021HIV/AIDS and hepatitis B are diseases with major epidemiological and social impacts, with important effects in the dentistry context. This study aimed to compare the...
INTRODUCTION
HIV/AIDS and hepatitis B are diseases with major epidemiological and social impacts, with important effects in the dentistry context. This study aimed to compare the knowledge, presence, and manifestation of discriminatory and stigmatizing acts of dental surgeons, dental assistants, and dental students concerning social representations of HIV/AIDS and hepatitis B.
METHODOLOGY
This cross-sectional, quantitative study was carried out in Brazil with primary health care dental surgeons (n = 219) and dental assistants (n = 152) in 40 municipalities and dental students of a public university (n = 179). The z-test for proportions (p ≤ 0.05) was used for data analysis to compare the three groups.
RESULTS
We found statistically significant differences regarding knowledge about HIV/AIDS and hepatitis B, with a higher percentage of correct answers by dental surgeons (97.7%). Regarding infection, the fear of contracting HIV/AIDS was more representative, whereas hepatitis B was more mentioned concerning the risk of infection. In general, only 30.7% and 42.2% of individuals would accept care from professionals with HIV/AIDS and hepatitis B, respectively; assistants and students had the higher proportion of refusal of care. Also, a higher proportion of assistants (47.4%) believed there are different conducts in the care of patients with HIV and hepatitis B.
CONCLUSIONS
The knowledge of individuals about infectious diseases is still inconsistent, especially among dental assistants and students. Moreover, these groups showed a silent and hidden presence and manifestation of discriminatory and stigmatizing attitudes, with greater representativeness for HIV/AIDS.
Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Brazil; Cross-Sectional Studies; Dental Assistants; Dentistry; Dentists; Educational Status; Female; HIV Infections; Health Knowledge, Attitudes, Practice; Hepatitis B; Humans; Male; Middle Aged; Students, Dental; Young Adult
PubMed: 34343123
DOI: 10.3855/jidc.12283 -
Cold Spring Harbor Perspectives in... Mar 2020Both genome sequencing (GS) and exome sequencing (ES) have proven to be revolutionary in the diagnosis of pediatric rare disease. The diagnostic potential and increasing... (Review)
Review
Both genome sequencing (GS) and exome sequencing (ES) have proven to be revolutionary in the diagnosis of pediatric rare disease. The diagnostic potential and increasing affordability make GS and ES more accessible as a routine clinical test in some centers. Herein, I review aspects of rare disease in pediatrics associated with the use of genomic technologies with an emphasis on the benefits and limitations of both ES and GS, complexities of variant classification, and the importance of genetic counseling. Indications for testing, the role of genetic counselors in genomic test selection, and the diagnostic potential of ES and GS in various pediatric multisystem disorders are discussed. The neonatal population represents an important cohort in pediatric rare disease. Rapid ES and GS in critically ill neonates can have an immediate impact on medical management and present unique genetic counseling challenges. This work includes reviews of recommendations for genetic counseling for families considering genome-wide sequencing, and issues of access to genetic counseling that affect clinical use and will necessitate implementation of innovative methods such as online decision aids. Finally, this work will also review the challenges of having a child with a rare disease, the impact of results from ES and GS on these families, and the role of various support agencies.
Topics: Adolescent; Child; Child, Preschool; Databases, Genetic; Genetic Counseling; Genetic Diseases, Inborn; Genetic Testing; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Pediatrics; Practice Guidelines as Topic; Rare Diseases; Exome Sequencing
PubMed: 31501267
DOI: 10.1101/cshperspect.a036632 -
The Journal of Experimental Medicine Oct 2022Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the...
Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
Topics: Humans; Interferon-gamma; Interleukin-23; Job Syndrome; TYK2 Kinase
PubMed: 36094518
DOI: 10.1084/jem.20220094