Nevin Manimala

Cell Immunol. 2021 Mar 23;364:104345. doi: 10.1016/j.cellimm.2021.104345. Online ahead of print.

ABSTRACT

Previously, we generated IL233, a hybrid cytokine composed of interleukin (IL)-2 and IL-33, with better therapeutic potential than either cytokine in multiple inflammatory diseases, in part through promoting T-regulatory cells (Tregs). Here we test the potential of IL233 pretreatment in a murine model of excessive Th1 activation, the parent-into-F1 model of acute GVHD (aGVHD). Five days of IL233 pretreatment of the recipients blocked or delayed the aGVHD-linked loss of B cells as seen in either the peripheral blood (day-11) or lymph nodes (day-14). IL233 pretreatment also prevented the expansion of donor CD8 T-cells in blood and LN at day-14 and significantly reduced day-14 serum IFNγ and TNFα compared to saline treated GVHD mice although, the level of Tregs did not statistically differ between saline and IL233-treated mice. Overall, the current study provides support for the use of IL233 as a therapeutic option in excessive Th1/CD8-driven conditions.

PMID:33831754 | DOI:10.1016/j.cellimm.2021.104345

Gait Posture. 2021 Mar 26;86:278-286. doi: 10.1016/j.gaitpost.2021.03.029. Online ahead of print.

ABSTRACT

BACKGROUND: Common etiologies for post-traumatic ankle osteoarthritis are ankle fractures and chronic ankle instability. As the nature of trauma is different for these two etiologies, it might be expected that the two subtypes of post-traumatic ankle osteoarthritis would display different foot mechanics during gait.

RESEARCH QUESTION: The objective of this exploratory cross-sectional study was to compare the foot kinematics and kinetics of patients suffering from post-fracture ankle osteoarthritis with those of patients suffering from post-sprain ankle osteoarthritis.

METHODS: Twenty-nine subjects with end-stage post-traumatic ankle osteoarthritis and fifteen asymptomatic control subjects participated in this study. All patients suffered from post-traumatic ankle osteoarthritis secondary to ankle-related fracture (Group 1; n = 15) or to chronic ankle instability (Group 2; n = 14). A four-segment kinematic and kinetic foot model was used to calculate intrinsic foot joint kinematics and kinetics during gait. Vector field statistical analysis MANOVA was used to assess differences between groups for the entire three-component intrinsic foot joint angles and moments.

RESULTS: MANOVA showed significant differences between the groups. Post-hoc analyses suggested that the differences between post-fracture ankle osteoarthritis group and controls were caused by a combination of less adducted Shank-Calcaneus position and less plantarflexion at this joint. Post-hoc analyses also suggested that both pathological groups exhibited a decreased plantarflexion moment for Shank-Calcaneus, Chopart, Lisfranc joints compared to controls. Analyses of both pathological groups versus controls for power suggested lower Shank-Calcaneus and Lisfranc power generation during pre-swing phase.

SIGNIFICANCE: No significant differences were found between the two pathological groups in this exploratory study. Alterations in foot kinematics and kinetics were mainly found about the dorsi-/plantarflexion axis during the pre-swing phase of the stance phase for both pathological groups compared to controls. Observed differences were not limited to the painful ankle joint, but seem also to have affected the kinetics of the neighbouring foot joints.

PMID:33831743 | DOI:10.1016/j.gaitpost.2021.03.029

Clin Transl Sci. 2021 Apr 8. doi: 10.1111/cts.12980. Online ahead of print.

ABSTRACT

The current success rate of a drug candidate, from the beginning of the clinical trial to receiving marketing approval, is about 10%-20%, and it has not changed during the past few decades. Therefore, pharmaceutical companies are under pressure to select one compound, among many others, with a high probability of success. The differences in drug features affect their probabilities of approval success. In this study, we examined the approval success rates of drug candidates, developed in the United States, the European Union, or Japan, by focusing on four parameters (“drug target,” “drug action,” “drug modality,” and “drug application”) and their combinations, and identified factors that conditioned the outcome of the drug development process. We obtained a total success rate of 12.8%, after evaluating 3999 compounds. Moreover, after analyzing the combinations of these parameters, the approval success rates of drugs that corresponded to the following categories-a stimulant in drug action or an enzyme in drug target and biologics (excluding monoclonal antibody) in drug modality-were high (34.1% and 31.3%, respectively). Univariate and multivariate logistic regression analyses revealed that stimulant in drug action, and “B” (blood and blood forming organs), “G” (genito-urinary system and sex), and “J” (anti-infectives for systemic use) in drug application were statistically associated with high approval success rates. We found several parameters and their combinations that affected drug approval success rates. Our results could assist pharmaceutical companies in evaluating the probability of success of their drug candidates and, thus, in efficiently conducting the clinical development process.

PMID:33831276 | DOI:10.1111/cts.12980

J Clin Psychol. 2021 Apr 8. doi: 10.1002/jclp.23137. Online ahead of print.

ABSTRACT

OBJECTIVES: Difficulties with sexual desire and arousal are common in women, but most lack access to effective treatment such as cognitive-behavioral therapy (CBT). eSense is a recently created online CBT intervention for sexual difficulties with promising evidence of usability. The current study assessed the feasibility of women completing the full eSense CBT program without guidance.

METHODS: Eleven women with Sexual Interest/Arousal Disorder completed eSense and provided feedback via semi-structured interviews.

RESULTS: Participants reported high satisfaction with eSense’s functionality, improved knowledge about sexuality, greater awareness of their thought patterns, and better perspective around their sexual difficulties. Despite some difficulty completing homework, participants exhibited statistically significant pre-post improvements in sexual desire (d = 1.04), sexual arousal (d = 1.83), sexual satisfaction (d = 1.35), and sexual distress (d = 1.79).

CONCLUSION: The findings add to the growing evidence that self-guided online interventions are feasible and potentially efficacious in treating female sexual dysfunction.

PMID:33831258 | DOI:10.1002/jclp.23137

Interact Cardiovasc Thorac Surg. 2021 Apr 8;32(3):371-379. doi: 10.1093/icvts/ivaa277.

ABSTRACT

OBJECTIVES: Depression is common in patients with cardiac disease. The importance of preoperative depression for development of postoperative delirium (POD) following cardiac surgery is not well known. The aim is to provide a summary estimate of depression as a predictor of POD following cardiac surgery.

METHODS: Systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection and Psycinfo (Ovid) was performed from inception to October 2019, including cohort studies reporting odds ratios (ORs) and 95% confidence intervals (CIs) for POD following cardiac surgery in patients with preoperative depression compared to patients without depression. ORs and 95% CIs for POD were calculated using random-effects meta-analyses. Subgroup and sensitivity analyses were performed.

RESULTS: Seven studies were included with a combined study population of 2066 patients. The pooled prevalence of POD in the combined study population was 26% and preoperative depression was present in ∼9% of the total study population. All studies showed a positive association between preoperative depression and POD; and in 5 studies, the association was statistically significant. Patients with depression had a pooled OR of 2.31 (95% CI 1.37-3.90) for POD.

CONCLUSIONS: This systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD.

PMID:33831217 | DOI:10.1093/icvts/ivaa277

Interact Cardiovasc Thorac Surg. 2021 Apr 8;32(3):343-350. doi: 10.1093/icvts/ivaa265.

ABSTRACT

OBJECTIVES: The inflammatory response after surgery is associated with patient prognosis. Patients who undergo thoracic surgery exhibit a profound systemic inflammatory response due to the surgical procedures used and application of one-lung ventilation. The aim of this study was to compare perioperative inflammatory changes in patients after intubated and non-intubated thoracic surgery for primary lung cancer resection.

METHODS: This prospective randomized controlled study included forty patients who underwent surgical resection for stage I non-small-cell lung cancer. Blood samples for cytokine analysis were collected just before induction, at 1 and 24 h after surgery. Levels of the pro-inflammatory cytokine and anti-inflammatory cytokines were measured using quantitative sandwich enzyme immunoassay kits.

RESULTS: The basal values of cytokines were comparable between 2 groups. Within each group, the postoperative levels of interleukin (IL)-1, IL-6 and tumour necrosis factor-α increased, while those of IL-4 and IL-10 did not change significantly. The levels of IL-6 and tumour necrosis factor-α were significantly lower in group NI at 1 and 24 h postoperatively. Other cytokines did not differ in both groups during postoperative period. The IL-6/IL-10 ratio at 1 h after surgery was lower in non-intubated patients than in intubated patients, but there was no difference at 24 h after surgery.

CONCLUSIONS: Non-intubated thoracic surgery may attenuate the early inflammatory cytokine changes following major resection for primary lung cancer compared with intubated conventional surgery.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT04007354.

PMID:33831216 | DOI:10.1093/icvts/ivaa265

J AOAC Int. 2021 Apr 8:qsab049. doi: 10.1093/jaoacint/qsab049. Online ahead of print.

ABSTRACT

BACKGROUND: The SureFast® SARS-CoV-2 PLUS Test is a reverse transcription qPCR (RT-qPCR) assay for the direct, qualitative detection of novel coronavirus (SARS-CoV-2) RNA from stainless steel environmental sample swabs.

OBJECTIVE: To validate the SureFast® SARS-CoV-2 PLUS Kit as part of the AOAC Research Institute’s Emergency Response Validation Performance Tested Method SM program.

METHODS: The SureFast® SARS-CoV-2 PLUS Kit was evaluated for specificity using in silico analysis of 15,764 SARS-CoV-2 sequences and 65 exclusivity organisms (both near neighbors and background organisms) using the ThermoBLAST program. The candidate method was evaluated in an unpaired study design for one environmental surface (stainless steel) and compared to the U.S. Centers for Disease Control and Prevention 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel, Instructions for Use (Revision 4, Effective 6/12/2020).

RESULTS: Results of the in silico analysis demonstrated 99.99% selectivity of the method in being able to detect target sequences of the known CoV-2 genomes and discriminate them from near neighbors. In the matrix study, the candidate method demonstrated statistically significant better recovery of the target analyte than the PCR detection reference method.

CONCLUSIONS: The SureFast® SARS-CoV-2 PLUS Kit is a rapid and accurate method that can be utilized by food producers to detect the causative agent of COVID-19 on stainless steel contact surfaces.

HIGHLIGHTS: SureFast® SARS-CoV-2 PLUS test method is highly specific for primer/probe binding to the E target genome region for the SARS-CoV-2 virus, 99.99% binding specificity using in silico analysis.

PMID:33831212 | DOI:10.1093/jaoacint/qsab049

Am J Epidemiol. 2021 Apr 8:kwab098. doi: 10.1093/aje/kwab098. Online ahead of print.

ABSTRACT

Serological surveys can provide evidence of cases that were not previously detected, depict the spectrum of disease severity, and estimate the proportion of asymptomatic infections. To capture these parameters, survey sample sizes may need to be very large, especially when the overall infection rate is still low. Therefore, we propose the use of “snowball sampling” to enrich serological surveys by testing contacts of infected individuals identified in the early stages of an outbreak. For future emerging pandemics, this observational study sampling design can answer many key questions, such as estimating the asymptomatic proportion of all infected cases, the probability of a given clinical presentation for a seropositive individual, or the association between characteristics of either the host or the infection and seropositivity among contacts of index individuals. We provide examples, in the context of the coronavirus disease 2019 (COVID-19) pandemic, of studies and analysis methods using a snowball sample and perform a simulation study that demonstrates scenarios where snowball sampling can answer these questions more efficiently than other sampling schemes. We hope such study designs can be applied to provide valuable information to slow the present pandemic as it enters its next stage and in early stages of future pandemics.

PMID:33831177 | DOI:10.1093/aje/kwab098

Am J Epidemiol. 2021 Apr 8:kwab101. doi: 10.1093/aje/kwab101. Online ahead of print.

ABSTRACT

Test-negative studies are commonly used to estimate influenza vaccine effectiveness (VE). In a typical study, an “overall VE” estimate may be reported based on data from the entire sample. However, there may be heterogeneity in VE, particularly by age. We therefore discuss the potential for a weighted average of age-specific VE estimates to provide a more meaningful measure of overall VE. We illustrate this perspective first using simulations to evaluate how overall VE would be biased when certain age groups are over-represented. We found unweighted overall VE estimates tended to be higher than weighted VE when children were over-represented and lower when elderly were over-represented. Then we extracted published estimates from the US Flu VE network, in which children are overrepresented, and some discrepancy between unweighted and weighted overall VE was observed. Differences in weighted versus unweighted overall VE could translate to substantial differences in the interpretation of individual risk reduction in vaccinated persons, and the total averted disease burden at the population level. Weighting overall estimates should be considered in VE studies in future.

PMID:33831173 | DOI:10.1093/aje/kwab101

PLoS One. 2021 Apr 8;16(4):e0250012. doi: 10.1371/journal.pone.0250012. eCollection 2021.

ABSTRACT

BACKGROUND: High maternal mortality is still a significant public health challenge in many countries of the South-Asian region. The majority of maternal deaths occur due to pregnancy and delivery-related complications, which can mostly be prevented by safe facility delivery. Due to the paucity of existing evidence, our study aimed to examine the factors associated with place of delivery, including women’s preferences for such in three selected South-Asian countries.

METHODS: We extracted data from the most recent demographic and health surveys (DHS) conducted in Bangladesh (2014), Nepal (2016), and Pakistan (2017-18) and analyzed to identify the association between the outcome variable and socio-demographic characteristics. A total of 16,429 women from Bangladesh (4278; mean age 24.57 years), Nepal (3962; mean age 26.35 years), and Pakistan (8189; mean age 29.57 years) were included in this study. Following descriptive analyses, bivariate and multivariate logistic regressions were conducted.

RESULTS: Overall, the prevalence of facility-based delivery was 40%, 62%, and 69% in Bangladesh, Nepal, and Pakistan, respectively. Inequity in utilizing facility-based delivery was observed for women in the highest wealth quintile. Participants from Urban areas, educated, middle and upper household economic status, and with high antenatal care (ANC) visits were significantly associated with facility-based delivery in all three countries. Interestingly, watching TV was also found as a strong determinant for facility-based delivery in Bangladesh (aOR = 1.31, 95% CI:1.09-1.56, P = 0.003), Nepal (aOR = 1.42, 95% CI:1.20-1.67, P<0.001) and Pakistan (aOR = 1.17, 95% CI: 1.03-1.32, P = 0.013). Higher education of husband was a significant predictor for facility delivery in Bangladesh (aOR = 1.73, 95% CI:1.27-2.35, P = 0.001) and Pakistan (aOR = 1.19, 95% CI: 0.99-1.43, P = 0.065); husband’s occupation was also a significant factor in Bangladesh (aOR = 1.30, 95% CI:1.04-1.61, P = 0.020) and Nepal (aOR = 1.26, 95% CI:1.01-1.58, P = 0.041).

CONCLUSION: Our findings suggest that the educational status of both women and their husbands, household economic situation, and the number of ANC visits influenced the place of delivery. There is an urgent need to promote facility delivery by building more birthing facilities, training and deployment of skilled birth attendants in rural and hard-to-reach areas, ensuring compulsory female education for all women, encouraging more ANC visits, and providing financial incentives for facility deliveries. There is a need to promote facility delivery by encouraging health facility visits through utilizing social networks and continuing mass media campaigns. Ensuring adequate Government funding for free maternal and newborn health care and local community involvement is crucial for reducing maternal and neonatal mortality and achieving sustainable development goals in this region.

PMID:33831127 | DOI:10.1371/journal.pone.0250012