Category: Nevin Manimala

Brief Bioinform. 2022 Jan 11:bbab572. doi: 10.1093/bib/bbab572. Online ahead of print.

ABSTRACT

With the increasing volume of human sequencing data available, analysis incorporating external controls becomes a popular and cost-effective approach to boost statistical power in disease association studies. To prevent spurious association due to population stratification, it is important to match the ancestry backgrounds of cases and controls. However, rare variant association tests based on a standard logistic regression model are conservative when all ancestry-matched strata have the same case-control ratio and might become anti-conservative when case-control ratio varies across strata. Under the conditional logistic regression (CLR) model, we propose a weighted burden test (CLR-Burden), a variance component test (CLR-SKAT) and a hybrid test (CLR-MiST). We show that the CLR model coupled with ancestry matching is a general approach to control for population stratification, regardless of the spatial distribution of disease risks. Through extensive simulation studies, we demonstrate that the CLR-based tests robustly control type 1 errors under different matching schemes and are more powerful than the standard Burden, SKAT and MiST tests. Furthermore, because CLR-based tests allow for different case-control ratios across strata, a full-matching scheme can be employed to efficiently utilize all available cases and controls to accelerate the discovery of disease associated genes.

PMID:35021184 | DOI:10.1093/bib/bbab572

Lifestyle Genom. 2022 Jan 12:1-10. doi: 10.1159/000519916. Online ahead of print.

ABSTRACT

INTRODUCTION: The oral cavity is home to a diverse and distinct microbiome. While the role of oral bacteria in cariogenic and other dental diseases is irrefutable, their beneficial effects in the form of probiotics (PB) has been less studied, especially pertaining to oral diseases in children. This study compares the efficacy of a PB mouthrinse with 0.12% chlorhexidine (CHX) and 0.05% sodium fluoride (NaF) mouthrinse on the colony counts of mutans streptococci (MS) in children.

METHODS: A triple-blind crossover randomized trial between interventional groups was planned. Fifty-one children between 8 to 12 years of age were divided into three groups (I, II, and III) and were exposed to all three mouthrinses (A, B, and C) by randomized allocation for a period of two weeks with an inter-phase washout period of four weeks. Pre- and post-interventional MS counts (CFU/mL) were assessed, and the mean change was analysed using the t test (intragroup) and ANOVA (intergroup and crossover).

RESULTS: The mean changes in the colony counts obtained with the use of PB, CHX, and NaF mouthrinses were -1.0223 (-1.2201 to -0.8246), -0.9564 (-1.1503 to -0.7626), and -0.9511 (-1.1554 to -0.7467), respectively, which were statistically significant (p < 0.0001). However, the intergroup comparison for the mean change in colony counts revealed no statistically significant differences (p > 0.05).

CONCLUSION: The study concluded that the PB mouthrinse was equally efficacious as compared to CHX and NaF mouthrinses against MS in 8- to 12-year-old children. However, further studies are recommended to strengthen the evidence.

PMID:35021171 | DOI:10.1159/000519916

Transplant Cell Ther. 2022 Jan 9:S2666-6367(22)00002-1. doi: 10.1016/j.jtct.2022.01.002. Online ahead of print.

ABSTRACT

Haploidentical related donor (HRD) is a common alternative donor strategy used when matched sibling or unrelated donors are not available for hematopoietic stem cell transplantation (HSCT). However, there have been no studies comparing HRD HSCT with post-transplant cyclophosphamide (PTCy) and matched unrelated donor (MUD) HSCT with antithymocyte globulin, using similar busulfan-based myeloablative conditioning regimen in pediatric acute leukemia. Here, we compared the outcomes in children and adolescents with high-risk acute leukemia after HRD HSCT with PTCy (n=35) and MUD HSCT (n=45) after targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring. The median follow-up times of the HRD and MUD groups were 3.7 and 4.6 years, respectively. No engraftment failure was observed in both groups. The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV (34.3% versus 48.9%, p=0.142), grades III-IV (2.9% vs. 8.9%, p=0.272), moderate to severe chronic GVHD (11.4% vs. 18.3%, p=0.417), relapse (25.6% vs. 28.0%, p=0.832), and non-relapse mortality (0% vs. 2.2%, p=0.420) were not significantly different between the two groups. The 3-year severe chronic GVHD-free/relapse-free (GRFS), leukemia-free (LFS) and overall survival (OS) rates in the HRD and MUD groups were 62.9% (95% confidence intervals [CI], 45.8%, 80.0%) versus 49.8% (95% CI, 34.9%, 64.7%; p=0.318), 74.4% (95% CI, 58.7%, 90.1%) versus 67.5% (95% CI, 53.4%, 81.6%; p=0.585), and 88.6% (95% CI, 78.0%, 99.2%) versus 83.7% (95% CI, 72.5%, 94.9%; p=0.968), respectively. In a subgroup analysis of acute lymphoblastic leukemia patients (HRD, n=17; MUD, n=26), the 3-year GRFS, LFS, and OS rates of the HRD and MUD groups were 49.4% (95% CI, 24.3%, 74.5%) versus 39.5% (95% CI, 19.7%, 59.3%; p=0.601), 61.8% (95% CI, 37.5%, 86.1%) versus 63.6% (95% CI, 44.4%, 82.8%; p=0.872), and 82.4% (95% CI, 64.4%, 100%) versus 84.2% (95% CI, 70.1%, 98.3%; p=0.445), respectively. In acute myeloid leukemia patients (HRD, n=16; MUD, n=16), the 3-year GRFS, LFS, and OS rates of the HRD and MUD groups were 80.8% (95% CI, 61.2%, 100%) versus 61.9% (95% CI, 37.8%, 86.0%; p=0.326), 87.1% (95% CI, 70.2%, 100%) versus 73.9% (95% CI, 51.8%, 96.0%; p=0.478), and 93.8% (95% CI, 81.8%, 100%) versus 85.6% (95% CI, 67.0%, 100%; p=0.628), respectively. Although the difference was not statistically significant and the number of patients was small, the promising outcomes of HRD HSCT in AML patients were encouraging. Our results demonstrated that HRD HSCT with PTCy using a targeted busulfan-based myeloablative conditioning shows outcomes similar to those of MUD HSCT with antithymocyte globulin. HRD HSCT with PTCy could be a feasible option for pediatric high-risk acute leukemia patients who lack an HLA-matched related or unrelated donor.

PMID:35021131 | DOI:10.1016/j.jtct.2022.01.002

Folia Phoniatr Logop. 2022 Jan 12. doi: 10.1159/000521906. Online ahead of print.

ABSTRACT

INTRODUCTION: Assessment of intelligibility in dysarthria tends to rely on oral reading of sentences or words. However, self-generated utterances are closer to a clients’ natural speech. This study investigated how transcription of utterances elicited by picture description can be used in the assessment of intelligibility in speakers with Parkinson’s disease.

METHODS: Speech samples from eleven speakers with Parkinson’s disease and six neurologically healthy persons were audio-recorded. Forty-two naive listeners completed transcriptions of self-generated sentences from a picture description task and orally read sentences from the Swedish Test of Intelligibility, as well as scaled ratings of narrative speech samples.

RESULTS: Intelligibility was higher in orally read than self-generated sentences and higher for content words than for the whole sentence in self-generated sentences for most of the speakers, although these within-group differences were not statistically significant at group level. Adding contextual leads for the listeners increased intelligibility in self-generated utterances significantly, but with individual variation. Although correlations between the intelligibility measures were at least moderate or strong, there was a considerable inter- and intra-speaker variability in intelligibility scores between tasks for the speakers with Parkinson’s disease, indicating individual variation of factors that impact intelligibility. Intelligibility scores from neurologically healthy speakers were generally high across tasks with no significant differences between the conditions.

DISCUSSION/CONCLUSION: Within-speaker variability support literature recommendations to use multiple methods and tasks when assessing intelligibility. The inclusion of transcription of self-generated utterances elicited by picture description to the intelligibility assessment has the potential to provide additional information to assessment methods based on oral reading of pre-scripted sentences, and to inform the planning of interventions.

PMID:35021169 | DOI:10.1159/000521906

Curr Probl Cardiol. 2022 Jan 9:101111. doi: 10.1016/j.cpcardiol.2022.101111. Online ahead of print.

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This pilot study assessed the association of OSA and invasive coronary microvascular function in patients with ischemia with no obstructive coronary artery disease (INOCA).

METHODS: Forty-two patients with angina, were prospectively screened at a single tertiary centre covering the northern metropolitan area of South Australia, from February 2018 to December 2020 (ACTRN12618000149268). Forty patients were invited into to this observational study after coronary angiography demonstrated INOCA and functional coronary vasomotor disorder (n = 40). Twenty one participants subsequently underwent a sleep study for OSA diagnosis while 9 participants had prior formal diagnosis of OSA (ACTRN12618000227291).

RESULTS: Of the 30 participants with OSA data, 87% (n=26) had a diagnosis of OSA. Accordingly, 11 with mild severity, 7 with moderate severity and 8 with severe OSA. No OSA was observed in 4 participants. Participants with OSA were older [61.4±8.7 vs 49.9±9.7, p=0.002] with similar clinical characteristics for the pattern and severity of angina and other co-morbidities. 73.3% (n=22) had abnormal functional disorders of the epicardial coronary arteries and/or coronary microcirculation. On multivariate analysis, OSA was the only statistically significant association with functional coronary microvascular disorders [OR 53.95, 1.41-2065.01, p=0.032].

CONCLUSION: This study provided an observation of a significant correlation between INOCA with abnormal coronary vasomotor function and OSA in an Australian cohort. This correlation supports a possible pathophysiological interplay between these two conditions that needs to be further evaluated. The benefit of treatment of OSA in this subset remains unknown.

PMID:35021111 | DOI:10.1016/j.cpcardiol.2022.101111

J Pain. 2022 Jan 9:S1526-5900(22)00002-5. doi: 10.1016/j.jpain.2021.12.011. Online ahead of print.

ABSTRACT

We examined the influence of negative psychological factors (catastrophizing, distress and kinesiophobia) on delayed onset muscle soreness (DOMS) intensity, cervical function (strength and range of motion) and on daily activities (ADL), and the suitability of an exercise protocol designed to induce DOMS within the cervical region. Psychological factors and cervical function were assessed in 86 healthy participants at baseline before applying a DOMS provocation protocol in the cervical flexor muscles. After 24h, cervical function was reassessed. In addition, at 24h and 48h, the intensity of DOMS and its impact on ADL were assessed using the visual analog scale (VAS). The protocol was effective given that it generated low-moderate intensity DOMS (VAS≈30-40mm) and a statistically significant reduction in cervical strength and range of motion. Psychological distress (anxiety and depression), but not kinesiophobia and catastrophism, predicted a loss of cervical strength (explained 43% of the variance) and range of motion (explained 22% of the variance) after induction of DOMS. In addition, participants’ anxiety level predicted DOMS intensity at 24h (explained 19% of the variance). Perspective The present findings highlight the relevance of evaluating psychological distress as a preventive/therapeutic measure, given that high levels of distress could lead to more intense and disabling pain in acute injuries, and all these aspects are considered risk factors for the chronification of symptoms.

PMID:35021115 | DOI:10.1016/j.jpain.2021.12.011

Acta Trop. 2022 Jan 9:106303. doi: 10.1016/j.actatropica.2022.106303. Online ahead of print.

ABSTRACT

In the present study, we evaluated the effects of antibodies anti-sandfly saliva on the fecundity of Phlebotomus papatasi, vector of zoonotic cutaneous leishmaniasis in the Old World. Rabbits were repeatedly exposed to sandfly bites. Immune sera showed increased levels of anti-sandfly saliva antibody compared to the pre-exposition period. The analysis of biological parameters revealed no decline on the feeding success of females P. papatasi fed on rabbits repeatedly exposed to sandfly bites. Our results showed that anti-sandfly saliva antibodies of rabbits are not detrimental to the fitness of females P. papatasi. Thus, rabbits did not acquire resistance to sandflies following repeated exposures, and that contribute in maintaining a high density of P. papatasi. To control sandfly infestations and Leishmania transmission, more studies are needed for a better understanding of the mechanisms governing the resistance of hosts to bites of sandflies.

PMID:35021103 | DOI:10.1016/j.actatropica.2022.106303

Cell. 2022 Jan 5:S0092-8674(21)01481-1. doi: 10.1016/j.cell.2021.12.018. Online ahead of print.

ABSTRACT

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.

PMID:35021063 | DOI:10.1016/j.cell.2021.12.018

Acta Med Port. 2022 Jan 12. doi: 10.20344/amp.15446. Online ahead of print.

ABSTRACT

INTRODUCTION: Pre-exposure prophylaxis (PrEP) has gained relevance as a method of prevention for HIV in certain people and settings. Following the publication of the guideline on PrEP prescribing in Portugal, we aimed to assess the knowledge of Portuguese Medical Students about PrEP.

MATERIAL AND METHODS: An online survey was sent to Medical students of Portuguese Medical Schools. We conducted a descriptive analysis of the results and an analytic cross-sectional study to identify factors associated with “knowing about PrEP”, “having had one class about PrEP” and “identifying eligible groups correctly”.

RESULTS: Of the 796 students that responded to the survey, 64.6% were aware of what PrEP is. Of these, 34.44% acquired this knowledge during their training. Out of the total amount of respondents, 4.77% could identify correctly and completely the eligible groups for PrEP. As the training years went by, the probability of being aware of PrEP, having had one class about PrEP, and identifying the eligible groups correctly, increased. Of the sixth-year students, 43.48% had had one class about PrEP and among the students that were aware of PrEP, 28% identified what the eligible groups were. After adjusting for the school year, we found differences between Medical Schools regarding the outcomes. The association between the different ways of learning about PrEP and the ability to correctly identify eligible groups for PrEP was not statistically significant.

CONCLUSION: The differences between Medical Schools could be harmonized through changes in the medical curricula that would allow this topic to be addressed more often.

PMID:35021038 | DOI:10.20344/amp.15446

Skin Res Technol. 2022 Jan 12. doi: 10.1111/srt.13133. Online ahead of print.

ABSTRACT

BACKGROUND: The elasticity of the dermal layer decreases with aging, leading to ulcer formation and wrinkling, but the mechanism of this change is not fully understood, because it is difficult to access the complex three-dimensional (3D) internal structure of the dermis.

OBJECTIVE: To clarify age-dependent changes in the overall 3D structure of the dermal layer by means of 3D analysis technology.

METHODS: We observed sun-protected human skin by means of X-ray micro CT, identified the layers of the skin, and reconstructed the 3D structure on computer. Age-dependent structural changes of the dermal layer were evaluated by statistical comparison of young and aged skin.

RESULTS: Histological observations suggested the presence of two types of ectopic fat deposits, namely infiltrated subcutaneous fat and isolated fat, in the lower region of the reticular dermal layer in aged skin. To elucidate their nature, we observed skin specimens by X-ray microCT. The epidermis, dermal layer, and subcutaneous adipose layer were well differentiated on CT images, and 3D skin was digitally reconstructed on computer. This method clearly showed that the isolated fat observed histologically was in fact connected to the subcutaneous fat, namely all ectopic fat is connected to the subcutaneous adipose layer. Statistical analysis showed that the severity of fat infiltration into dermal layer is significantly increased in aged skin compared with young skin.

CONCLUSION: Our findings indicate that subcutaneous fat infiltrates into the dermal layer of aged skin. Our 3D analysis approach is advantageous to understand changes of complex internal skin structures with aging.

PMID:35020969 | DOI:10.1111/srt.13133