Nevin Manimala

Pediatr Blood Cancer. 2021 Dec 28:e29522. doi: 10.1002/pbc.29522. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a known complication for children with acute lymphoblastic leukemia (ALL). The aim of this study was to identify laboratory biomarkers that predict which children with ALL are at risk for VTE during induction chemotherapy.

MATERIALS AND METHODS: Newly diagnosed ALL patients admitted to Children’s Hospital Los Angeles with a central venous catheter (CVC) were eligible to participate. Participants’ blood samples (complete blood count [CBC], quantitative D-dimer, prothrombin fragment 1.2 [PTF 1.2], and thrombin-antithrombin complexes [TAT]) were collected at day 0 (baseline/prior to induction), day 7 (±2 days), day 14 (±2 days), day 21 (±2 days), and day 28 (±2 days) of induction chemotherapy or until participants presented with a symptomatic VTE.

RESULTS: Seventy-five participants aged 1-21 years were enrolled and included in the final analysis. Twenty-six (35%) of the 75 participants were diagnosed with a CVC-associated VTE (22 asymptomatic and four symptomatic). There was a statistically significant difference between VTE and non-VTE participants for D-dimer (odds ratio [OR] 1.61, 95% confidence interval [CI]: 1.59-1.64), TAT (OR 1.34, 95% CI: 1.32-1.38), and PTF 1.2 (OR 1.31, 95% CI: 1.25-1.37) at all time points. Participants >10 years had a significantly higher risk of developing a VTE compared to participants <4 years (p = .007).

CONCLUSION: Older children with ALL as well as those with an elevated TAT, PTF 1.2, or D-dimer showed an increased risk of VTE, which may hold potential for predicting VTE in future studies.

PMID:34963026 | DOI:10.1002/pbc.29522

Oper Dent. 2021 Dec 28. doi: 10.2341/20-138-L. Online ahead of print.

ABSTRACT

This study evaluated the influence of new monomers derived from cashew nut shell liquid (CNSL) applied for dentin biomodification on resin-dentin bond strength, nanoleakage, and micropermeability to sound and artificially-created caries-affected dentin. Human dentin specimens were assigned to five groups, according to the following dentin pretreatment solutions: Absolute ethanol (control), 2 wt% grape seed extract (Vitis vinifera), 2 wt% cardol [from cashew nut shell liquid (CNSL)], 2 wt% cardol-methacrylate or 2 wt% cardanol-methacrylate applied on sound and artificial caries-affected dentin. Specimens were analyzed after 24 hour or 1 year of water storage. Microtensile bond strength (μTBS) (n=6), interface micropermeability (n=3), and silver nanoleakage (n=6) were assessed using a universal testing machine, confocal laser scanning microscope, and scanning electron microscope, respectively. In sound dentin, no difference in bond strength was observed between the groups in either storage period. In artificial caries-affected dentin, pretreatment with cardol-methacrylate resulted in statistically higher bond strength than all the other treatments in both storage periods. Cardol-methacrylate treatment resulted in less nanoleakage, along with improved interfacial integrity, compared to further treatments in artificial caries-affected dentin. Regarding micropermeability analysis, all treatments depicted deficient sealing ability when applied on artificial caries-affected dentin, with the presence of gaps in the control group. In conclusion, cardol-methacrylate is a promising plant-derived monomer to reinforce the hybrid layer, since it preserved resin-dentin bond strength and improved dentin bonding, especially to caries-affected dentin, a well-known harsh substrate for adhesion longevity.

PMID:34963010 | DOI:10.2341/20-138-L

J Natl Cancer Inst. 2021 Dec 28:djab231. doi: 10.1093/jnci/djab231. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer patients are at risk of secondary therapy-related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)-associated genes are t-MN risk factors and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH-associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity.

METHODS: We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH-associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided.

RESULTS: Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH-associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P < .001; TP53: mean [SD] =2.83 [1.33] vs 1.07 [1.01], P < .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH-associated gene mutations was observed.

CONCLUSION: A positive gBRCA1/2 mutation status is not a risk factor to acquire CH-associated gene mutations. OC patients may benefit from monitoring CH-associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.

PMID:34963005 | DOI:10.1093/jnci/djab231

Gerontologist. 2021 Dec 28:gnab187. doi: 10.1093/geront/gnab187. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Tools to measure self-perceived communication between persons with early-stage dementia and their caregivers are lacking. Therefore, we developed a questionnaire for Experienced Communication in Dementia (ECD) with a patient version (ECD-P) and a caregiver version (ECD-C), that contains items on (1) caregiver competence, (2) social communication, (3) communication difficulties, and (4) experienced emotions. This article describes the feasibility and clinimetric evaluation of this instrument.

RESEARCH DESIGN AND METHODS: A prospective observational cohort study was conducted with 57 dyads (community-dwelling person with dementia and primary caregiver). ECD-P, ECD-C, and measures on quality of life, caregiver burden, cognitive functioning, physical functioning, and functional independence were administered. After two weeks, the dyads filled out the ECD again. Feasibility (completion time and missing values per item), internal consistency (Cronbach’s α), test-retest reliability (intraclass correlation coefficients (ICCs)) and construct validity (hypotheses testing with Spearman’s r) were evaluated.

RESULTS: Mean completion time was ten minutes per questionnaire. ICCs for test-retest reliability ranged from 0.67 to 0.78, except for ECD-P2 (ICC = 0.31). Internal consistency ranged from α = 0.75 to 0.82 for ECD-P1 and all parts of ECD-C, except for ECD-P2 (α = 0.66). Correlation coefficients for convergent validity ranged from r = 0.31 to 0.69 and correlation coefficients for divergent validity were r < 0.20 and statistically insignificant.

DISCUSSION AND IMPLICATIONS: Pending future research, the ECD, except part ECD-P2, seems to be a promising tool to measure experienced communication between persons with early-stage dementia and their caregivers.

PMID:34962993 | DOI:10.1093/geront/gnab187

J Infect Dis. 2021 Dec 28:jiab629. doi: 10.1093/infdis/jiab629. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after HIV infection compared to adults.

METHODS: We evaluated plasma from 212 ART-naïve, children living with HIV (1-3 years-old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity and IgG subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay.

RESULTS: 1-year-old children demonstrated neutralization breadth comparable to chronically-infected adults, while 2 and 3-year olds exhibited significantly greater neutralization breadth (p=0.014). Similarly, binding antibody responses increased with age, with levels in 2 and 3 year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. Interestingly, the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, suggesting most children may develop a polyclonal neutralization response.

CONCLUSIONS: These results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.

PMID:34962990 | DOI:10.1093/infdis/jiab629

Genome Biol Evol. 2021 Dec 28:evab287. doi: 10.1093/gbe/evab287. Online ahead of print.

ABSTRACT

Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 core-genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 core-genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 core-genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 core-genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009-2011 and again during the 2012-2013 time, facilitating the clonal expansion of this core-genogroup with AZMrs in the U.S. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the U.S. and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young core-genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers.

PMID:34962987 | DOI:10.1093/gbe/evab287

J Anim Sci. 2021 Dec 1;99(12):skab347. doi: 10.1093/jas/skab347.

ABSTRACT

A study investigating the use of a nonviable Lactobacillus acidophilus (NVL: Culbac; TransAgra, Storm Lake, IA) and a mixed prebiotic (MP) blend (beet pulp, fructooligosaccharide (FOS), mannanoligosaccharide (MOS), inulin, and kelp) was done to evaluate changes in fecal microbiota, fermentative end products, and gut immune health in healthy female and male adult Beagle dogs (n = 24; 5.74 ± 2.18 yr; 9.30 ± 1.32 kg). The study protocol was first approved by the facility’s Institutional Animal Care and Use Committee (Summit Ridge Farms; Susquehanna, PA) and followed throughout. Each of four test diets (control, NVL, MP, and MP + NVL [formulated to crude protein 25%, crude fat 14%, crude fiber 10% as-fed]) was fed once daily to maintain body weight for 21 d in a randomized-crossover design (four treatment periods and four washout periods). Fecal samples were collected on days 0 and 21 only for immunoglobulin A (IgA) and microbiota evaluation (16S rRNA V4 region and qPCR for Escherichia coli and Bifidobacterium), and fecal fermentative end-products and fecal pH were assessed only on day 21. Over the test periods, apparent total tract nutrient digestibility and stool quality were assessed. Data were analyzed by ANOVA (SAS v9.4, Cary, NC) or Kruskal-Wallis for between-diet effects, and paired t-test or Wilcoxon for time effects. Statistical significance was set at P ≤ 0.05. Apparent total tract nutrient digestibility revealed feeding MP-containing diets resulted in lower (P < 0.05) crude protein and fat digestibility vs. control and NVL diets. When dogs were fed MP, they had lower (P < 0.05) fecal pH compared with control and NVL diets, whereas fecal pH was lower in (P < 0.05) MP + NVL- vs. NVL-fed dogs. Fecal E. coli was (P < 0.05) lower at day 21 vs. day 0 when dogs were fed MP. Fecal Fusobacterium spp. was lower (P < 0.05) in both MP diets vs. control. Fecal Lactobacillus spp. increased (P < 0.05) from baseline with MP. Both diets with MP elicited greater (P < 0.05) fecal acetate and propionate concentration vs. control diet. At day 21, fecal IgA was greater (P < 0.05) in MP and MP + NVL compared with NVL diet. Only when dogs were fed MP did they have increased (P < 0.05) fecal IgA from day 21 vs. day 0. The MP + NVL diet decreased (P < 0.05) fecal isovalerate, isobutyrate, phenol, and indole vs. control. Overall, the MP elicited the most changes on microbiota, fermentative end-products, and IgA. Further investigation into NVL’s gut health benefits is warranted.

PMID:34962977 | DOI:10.1093/jas/skab347

PLoS One. 2021 Dec 28;16(12):e0261936. doi: 10.1371/journal.pone.0261936. eCollection 2021.

ABSTRACT

BACKGROUND: Birth-preparedness and complication-readiness (BPCR) is the process of planning for normal birth and anticipating the actions needed in case of an emergency. The involvement of husband during pregnancy helps a mother to make timely decisions to avoid delays. Identifying the level of husband involvement in Birth-preparedness and complication-readiness is very important, as husband is the major decision maker in household and health service related issue. However, there is no sufficient data in the Kucha district, which describes the level of husband involvement in Birth-preparedness and complication-readiness. Therefore, this study assessed the level of husband involvement in birth preparedness and complication readiness in Kucha District, Gamo Zone, Ethiopia.

METHODS: Community-based cross-sectional study was conducted on 421 husbands whose wife gave birth within the last 12 months at Kucha District using simple random sampling technique. Data was collected using a pretested interviewer-administered questionnaire by trained data collectors. Binary and multivariable logistic regression with odds ratios along with the 95% confidence interval analysis were employed to find factors associated with the level of husband involvement. A p-value <0.05 with 95% confidence level used to decide statistical significance.

RESULTS: Data were collected from 421 study participants. One hundred twenty-seven (30.2%) were involved in birth preparedness and complication readiness plan. Participants who had at least secondary school education AOR = 3.1, CI (1.84-5.23), had at least four antenatal care visits AOR = 4.91, CI (2.36-10.2), and live more than five km from the health care facility AOR = 2.35, CI = 1.40-3.96) were involved in birth preparedness and complication readiness plan.

CONCLUSION: Husbands’ involvement in birth preparedness and complication readiness was low. Husband’s higher educational level, high frequency of antenatal care, and long distance to the health facility were significantly associated with husbands’ involvement in Birth-preparedness and complication-readiness plan. Therefore, advocating for higher frequency of antenatal care and improving educational level are important to increase husbands’ involvement in birth preparedness and complication readiness plan.

PMID:34962971 | DOI:10.1371/journal.pone.0261936

PLoS One. 2021 Dec 28;16(12):e0261824. doi: 10.1371/journal.pone.0261824. eCollection 2021.

ABSTRACT

Bacterial sexually transmitted infections (STIs) continue to be a worsening public health concern in the United States (US). Though the national incidence of HIV infection has decreased over recent years, that of chlamydia, gonorrhea, and syphilis have not. Despite national recommendations on prevention, screening, and treatment of these STIs, these practices have not been standardized. Nine Health Resources and Services Administration Ryan White HIV/AIDS Program funded clinics across 3 US jurisdictions (Florida, Louisiana, and Washington, DC), were selected as clinical demonstration sites to be evaluated in this mixed method needs assessment to inform a multi-site, multi-level intervention to evaluate evidence-based interventions to improve STI screening and testing of bacterial STIs among people with or at risk for HIV. These 3 US jurisdictions were selected due to having higher than national average incidence rates of HIV and bacterial STIs. Descriptive statistics and deductive analysis were used to assess quantitative and qualitative needs assessment data. Results indicate the following needs across participating sites: inconsistent and irregular comprehensive sexual behavior history taking within and among sites, limited routine bacterial STI testing (once/year and if symptomatic) not in accordance with CDC recommendations, limited extragenital site gonorrhea/chlamydia testing, limited annual training on STI-related topics including LGBTQ health and adolescent/young adult sexual health, and limited efforts for making high-STI incidence individuals feel welcome in the clinic (primarily LGBTQ individuals and adolescents/young adults). These findings were used to identify interventions to be used to increase routine screenings and testing for bacterial STIs.

PMID:34962965 | DOI:10.1371/journal.pone.0261824

PLoS One. 2021 Dec 28;16(12):e0261813. doi: 10.1371/journal.pone.0261813. eCollection 2021.

ABSTRACT

In the present article we use geometric microliths (a specific type of arrowhead) and Approximate Bayesian Computation (ABC) in order to evaluate possible origin points and expansion routes for the Neolithic in the Iberian Peninsula. In order to do so, we divide the Iberian Peninsula in four areas (Ebro river, Catalan shores, Xúquer river and Guadalquivir river) and we sample the geometric microliths existing in the sites with the oldest radiocarbon dates for each zone. On this data, we perform a partial Mantel test with three matrices: geographic distance matrix, cultural distance matrix and chronological distance matrix. After this is done, we simulate a series of partial Mantel tests where we alter the chronological matrix by using an expansion model with randomised origin points, and using the distribution of the observed partial Mantel test’s results as a summary statistic within an Approximate Bayesian Computation-Sequential Monte-Carlo (ABC-SMC) algorithm framework. Our results point clearly to a Neolithic expansion route following the Northern Mediterranean, whilst the Southern Mediterranean route could also find support and should be further discussed. The most probable origin points focus on the Xúquer river area.

PMID:34962962 | DOI:10.1371/journal.pone.0261813