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Nevin Manimala Statistics

Immunopathogenesis and immunobiology of SARS-CoV-2

Infez Med. 2021 Jun 1;29(2):167-180.

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), in a very short span of thirteen months has taken a considerable toll on humanity, resulting in over 3 million deaths with more than 150 million confirmed cases as on May 1, 2021. In the scarcity of a potential antiviral and protective vaccine, COVID-19 has posed high public health concerns, panic, and challenges to limit the spread of this pandemic virus. Only recently have a few vaccine candidates been developed, and vaccination programs have started in some countries. Multiple clinical presentations of COVID-19, animal spillover, cross-species jumping, zoonotic concerns, and emergence of virus variants have altogether created havoc during this ongoing pandemic. Several bodies of research are continuously working to elucidate the exact molecular mechanisms of the pathogenesis. To develop a prospective antiviral therapy/vaccine for SARSCoV-2, it is quite essential to gain insight into the immunobiology and molecular virology of SARS-CoV-2. A thorough literature search was conducted up to 28th February 2021 in the PubMed and other databases for the articles describing the immunopathology and immune response of SARS-CoV-2 infection, which were critically evaluated and used to compile this article to present an overall update. Some of the information was drawn from studies on previous MERS and SARS viruses. Innate as well as adaptive immunity responses are elicited by exposure to SARS-CoV-2. SARS-CoV-2 establishes a successful infection by escaping the host immunity as well as over activating the innate immune mechanisms that result in severe disease outcomes, including cytokine storm. This review summarizes the immunopathology and molecular immune mechanisms elicited during SARS-CoV-2 infection, and their similarities with MERS-CoV and SARS-CoV.

PMID:34061781

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QuantiFERON-TB and tuberculin skin test in patients with active tuberculosis: the experience of a single medium-sized Italian University Hospital

Infez Med. 2021 Jun 1;29(2):229-235.

ABSTRACT

Interferon-γ releasing assays (IGRAs) are currently widely employed in the initial work up of Mycobacterium tuberculosis infection, as well as in suspected tuberculosis (TB). These assays are commonly utilized over the Tuberculin Skin Test (TST) in high resource and low TB burden settings, despite the unclear benefits shown in such contexts. The debate on the use of TST and IGRAs is of current interest also in Italy due to the increasing presence of immigrants from countries with a high incidence of TB and the rising attention of health care institutions to economic costs. The aim of this study was to compare QuantiFERON-TB (QFT) and TST results in active TB. We evaluated QFT results and TST reactions from 245 consecutive patients having both tests, registered among 411 patients admitted for TB at the Infectious Disease Clinic, Department of Medicine of the University of Perugia (Italy). We compared the rates of positive QFT and TST tests and noted no statistically significant differences overall or in relation to age, gender, HIV status and TB localization. Among foreign-born patients with confirmed TB, we observed a lower rate of positive TST results. The results of our study indicated that both QFT and TST can be used in the work up of TB having special attention when evaluating foreign-born patients.

PMID:34061788

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Nevin Manimala Statistics

Structural Parameter Standard Error Estimation Method in Diagnostic Classification Models: Estimation and Application

Multivariate Behav Res. 2021 Jun 1:1-20. doi: 10.1080/00273171.2021.1919048. Online ahead of print.

ABSTRACT

The information matrix or its inverse variance-covariance matrix for the maximum likelihood estimates of model parameters in diagnostic classification models plays a key role in statistical inference. Although both the item and structural parameters should be contained in the calculation of the information matrix simultaneously, previous studies have mainly focused on performance of the item parameter standard error (SE), no study has investigated the structural parameter SE estimation methods systematically. In this study, we propose a class of structural parameter SE estimation methods based on the empirical cross-product matrix, the observed information matrix, and the sandwich-type covariance matrix. A simulation study was conducted under different attribute hierarchy structures, the findings suggest that the proposed methods are useful for empirical researchers and practitioners in evaluating the variability of structural parameter estimators. We illustrate the application of the structural parameter SE estimation methods for exploring the presence of an attribute hierarchy using real data.

PMID:34061682 | DOI:10.1080/00273171.2021.1919048

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Disseminating Evidence on Abortion Facilities to Health Departments: A Randomized Study of E-mail Strategies

Health Commun. 2021 Jun 1:1-10. doi: 10.1080/10410236.2021.1932109. Online ahead of print.

ABSTRACT

Given the politicization of abortion, professionals working in U.S. health departments (HDs) may not be receptive to communications about abortion, despite often regulating abortion facilities. This paper reports results of a randomized, prospective, observational study to test the effects of e-mail language when disseminating evidence on abortion to HD professionals. Our sample was 302 HD employees who oversee healthcare facilities inspection/regulation in all 50 U.S. state HDs, clustered by HD and randomized into two study groups. In November-December 2019, we sent biweekly e-mails containing links to a website summarizing evidence on abortion facility regulation. E-mails/headers sent to one group emphasized public health values and did not include the word abortion; e-mails/headers to the other group used the word abortion. Primary outcome measures were e-mail open rates and click-through rates. Among 221 participants to whom e-mails were deliverable, the overall open rate was 36%. Open rate was 25% for PH values and 46% for abortion groups (p < .05). Effects were moderated by state abortion policy environment: in both supportive and restrictive environments, participants in the abortion messaging group were statistically more likely to open e-mails than those in the PH values group. There was no difference between groups in states with middle-ground abortion policy environments. Among participants opening at least one e-mail, 19% clicked through to the website, with no significant difference by group. This study demonstrates that repeated targeted e-mail campaigns can reach HD professionals with research summaries. Concerns that communications to HDs should avoid the word abortion are unsupported.

PMID:34061693 | DOI:10.1080/10410236.2021.1932109

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Relationship between natural or iatrogenic malocclusions and temporomandibular disorders: A case control study

Cranio. 2021 Jun 1:1-9. doi: 10.1080/08869634.2021.1933307. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the link between malocclusions and temporomandibular disorders (TMD) with a focus on iatrogenic malocclusion. Other etiologies of TMD (oral parafunctions) were also assessed.

METHODS: The prevalence of malocclusions was correlated in two groups: patients with TMD (case group) and patients without TMD (control group). Malocclusions involving dental care were specified. Parafunctions in the case group were assessed.

RESULTS: A statistically significant association between TMD and overbite >4 mm, interferences in laterotrusion, and absence of Angle Class I was shown. A potential deleterious effect of iatrogenic malocclusions was highlighted.

CONCLUSION: The multifactorial etiology of TMD was confirmed because an association between TMD and three malocclusions was found, and all case patients had parafunction(s). Current recommendations advising first a reversible treatment, TMD care should start with a behavioral re-education to remove parafunctions. However, it is essential to avoid creating iatrogenic malocclusion during dental care.

PMID:34061714 | DOI:10.1080/08869634.2021.1933307

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Moving Beyond 3+3: The Future of Clinical Trial Design

Am Soc Clin Oncol Educ Book. 2021 Jun;41:e133-e144. doi: 10.1200/EDBK_319783.

ABSTRACT

Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision. Beyond statistical simulations, there are little data to refute the supposed shortcomings ascribed to the 3+3 method. Even so, to address the unique nuances of gene- and immune-targeted compounds, a variety of inventive phase 1 trial designs have been suggested. Strategies for developing these therapies have launched first-in-human studies devised to acquire a breadth of patient data that far exceed the size of a typical phase I design and blur the distinction between dose selection and efficacy evaluation. Recent phase I trials of promising cancer therapies assessed objective tumor response and durability at various doses and schedules as well as incorporated multiple expansion cohorts spanning a variety of histology or biomarker-defined tumor subtypes, sometimes resulting in U.S. Food and Drug Administration approval after phase I. This article reviews recent innovations in phase I design from the perspective of multiple stakeholders and provides recommendations for future trials.

PMID:34061563 | DOI:10.1200/EDBK_319783

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Cannabis Varieties Can Be Distinguished by Achene Shape Using Geometric Morphometrics

Cannabis Cannabinoid Res. 2021 May 31. doi: 10.1089/can.2020.0172. Online ahead of print.

ABSTRACT

Introduction: Cannabis plant uses are widespread across human cultures. The current tendency is to classify Cannabis varieties into chemovars upon their chemical fingerprint, mainly cannabinoids and terpenoids content. The identification of chemovars has important medical implications; however, their pharmacological characterization is costly and time consuming. The goal of this study was to assess whether achene shape variation could be related to Cannabis varieties with contrasting cannabinoid concentrations, as a first approach to chemovar identification. Methods: We used two-dimensional geometric morphometrics (GM) of the achenes and multivariate statistical analysis. We used achenes from five varieties, two from Type II chemotype (expressing both tetrahydrocannabinol [THC] and cannabidiol [CBD]), two Type I (THC-only), and one Type III (CBD-only). Results: The achenes from the different chemotypes were clearly distinguishable. No significant differences between varieties from the same chemotype were observed. The varieties with high THC concentration (Type I) were rounded and bigger, whereas achene from varieties containing only CBD (Type III) had a slender shape with smaller size. Conclusion: Achene shape variation is a potential biomarker of cannabinoid content in the plant flowers. Further studies are needed to confirm the suitability of GM methods for high-throughput screening of Cannabis cultivars, including larger diversity of varieties, and taking into account growth conditions, which can also influence plant chemical fingerprint.

PMID:34061660 | DOI:10.1089/can.2020.0172

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Emergency Medical Services Communication Barriers and the Deaf American Sign Language User

Prehosp Emerg Care. 2021 Jun 1:1-13. doi: 10.1080/10903127.2021.1936314. Online ahead of print.

ABSTRACT

ObjectiveWe sought to identify current Emergency Medical Services (EMS) practitioner comfort levels and communication strategies when caring for the Deaf American Sign Language (ASL) user. Additionally, we created and evaluated the effect of an educational intervention and visual communication tool on EMS practitioner comfort levels and communication.MethodsThis was a descriptive study assessing communication barriers at baseline and after the implementation of a novel educational intervention with cross-sectional surveys conducted at three time points (pre-, immediate-post, and three months post-intervention). Descriptive statistics characterized the study sample and we quantified responses from the baseline survey and both post-intervention surveys.ResultsThere were 148 EMS practitioners who responded to the baseline survey. The majority of participants (74%; 109/148) previously responded to a 9-1-1 call for a Deaf patient and 24% (35/148) reported previous training regarding the Deaf community.The majority felt that important details were lost during communication (83%; 90/109), reported that the Deaf patient appeared frustrated during an encounter (72%; 78/109), and felt that communication limited patient care (67%; 73/109). When interacting with a Deaf person, the most common communication strategies included written text (90%; 98/109), friend/family member (90%; 98/109), lip reading (55%; 60/109), and spoken English (50%; 55/109).Immediately after the training, most participants reported that the educational training expanded their knowledge of Deaf culture (93%; 126/135), communication strategies to use (93%; 125/135), and common pitfalls to avoid (96%; 129/135) when caring for Deaf patients.At 3 months, all participants (100%, 79/79) reported that the educational module was helpful. Some participants (19%, 15/79) also reported using the communication tool with other non-English speaking patients.ConclusionsThe majority of EMS practitioners reported difficulty communicating with Deaf ASL users and acknowledged a sense of patient frustration. Nearly all participants felt the educational training was beneficial and clinically relevant; three months later, all participants found it to still be helpful. Additionally, the communication tool may be applicable to other populations that use English as a second language.

PMID:34060987 | DOI:10.1080/10903127.2021.1936314

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Estrogen Receptor 1 Gene rs22346939 and rs9340799 Variants are associated with Major Depressive Disorder and its Clinical Features

Curr Neurovasc Res. 2021 May 31. doi: 10.2174/1567202618666210531122239. Online ahead of print.

ABSTRACT

OBJECTIVE: Major depressive disorder (MDD) is a major health problem worldwide. Estrogen interacts with the central nervous system and has been shown to affect anxiety and depressive behavior. Estrogen mediates its effects by connecting its receptors, estrogen receptors 1 and 2. The purpose of this case-control study was to clarify the association between MDD risk and estrogen receptor 1 (ESR1) gene variants.

METHODS: This study included 245 individuals (125 MDD patients and 120 healthy controls). Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technics were used for genotyping ESR1 XbaI (rs9340799) and PvuII (rs22346939) variants.

RESULTS: There were statistically significant differences between the groups in terms of genotype frequencies of the ESR1 PvuII (-397 T > C) variant (p = 0.049) but not for the XbaI (-351 A > G) variant (p > 0.05). However, a correlation was observed between MDD and ESR1 XbaI variant after male participants were excluded (p = 0.028). Also, the high pain score of MDD patients was associated with the ESR1 PvuII variant, especially in female patients (p = 0.021). According to the results of combined genotype analysis, AA-TC combined genotype was correlated with a decreased risk in patients with MDD compared to controls (p = 0.016), while the combined genotype of GG-CC was associated with increased risk in the patients with MDD compared to controls (p = 0.042).

CONCLUSION: The two ESR1 variants were associated with MDD risk and its features in both individual and combined forms.

PMID:34060989 | DOI:10.2174/1567202618666210531122239

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Serum levels of ARMS2, COL8A1, RAD51B, and VEGF and their correlations in Age-Related Macular Degeneration

Curr Neurovasc Res. 2021 May 31. doi: 10.2174/1567202618666210531130711. Online ahead of print.

ABSTRACT

BACKGROUND: Many factors including genetic and environmental are responsible for the incidence of age-related macular degeneration (AMD). However, its pathogenesis has not been clearly elucidated yet.

OBJECTIVE: This study aimed to estimate the Age-Related Maculopathy Susceptibility 2 (ARMS2), Collagen type VIII Alpha 1 chain (COL8A1), Rad 51 paralog(RAD51B), and Vascular Endothelial Growth Factor (VEGF) protein levels in serum of AMD and control participants and to further investigate their correlation to understand AMD pathogenesis.

METHODS: For this cross-sectional study, 31 healthy control and 57 AMD patients were recruited from Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A blood sample was taken and serum was isolated from it. ELISA(enzyme-linked immunosorbent assay)was used for the estimation of proteins in the serum of patients.

RESULTS: ARMS2 and COL8A1 levels were significantly elevated in the AMD group than in the control group. The highest levels of ARMS2, COL8A1, and VEGF proteins were recorded for the wet AMD sub-group. The study results endorsed significant positive correlation between these following molecules; ARMS2 and COL8A1 (r=0.933, p<0.0001), ARMS2 and RAD51B (r=0.704, p<0.0001), ARMS2 and VEGF (r=0.925, p<0.0001), COL8A1 and RAD51B (r=0.736, p<0.0001), COL8A1 and VEGF (r=0.879, p<0.0001),and RAD51B and VEGF (r=0.691, p<0.0001).

CONCLUSION: The ARMS2 and COL8A1 levels were significantly higher and RAD51B was significantly lower in the AMD group than controls. Also, a significant statistical correlation was detected between these molecules, indicating that their interaction may be involved in the pathogenesis of AMD.

PMID:34060991 | DOI:10.2174/1567202618666210531130711