Nevin Manimala

Scand J Pain. 2021 May 21. doi: 10.1515/sjpain-2020-0014. Online ahead of print.

ABSTRACT

OBJECTIVES: It has been hypothesised that attentional bias to environmental threats can contribute to persistent pain. It is unclear whether people with acute low back pain (LBP) have an attentional bias to environmental threats. We investigated if attentional bias of threat related words is different in people with acute LBP and pain-free controls.

METHODS: People with acute LBP and pain-free people completed a free viewing eye tracking task. Participants were simultaneously presented with two words, a threat related word and a neutral control word. Threat related words were general threat, affective pain and sensory pain. We conducted linear mixed models to detect differences between acute LBP and pain-free participants on five eye tracking outcome measures (dwell time, first fixation, latency to first fixation, first run dwell time and number of fixations). We calculated absolute reliability, (standard error of measure), and relative reliability (intraclass correlation coefficients [ICC 2,1]) for each eye tracking outcome measures.

RESULTS: We recruited 65 people with acute LBP and 65 pain-free controls. Participants with acute LBP had a higher proportion of fixations towards the affective pain words (M=0.5009, 95% CI=0.4941, 0.5076) than the pain-free controls had (M=0.4908, 95% CI=0.4836, 0.4979), mean between group difference = -0.0101, 95% CI [-0.0198, -0.0004], p=0.0422. There was no difference between acute LBP and pain-free controls for the remaining eye tracking outcome measures (all p>0.05). The only outcome measure that had an ICC of more than 0.7 was the latency to first fixation (affective pain words ICC=0.73, general threat words ICC=0.72).

CONCLUSIONS: When compared with pain-free controls, people with acute LBP looked more often at affective pain words relative to neutral control words. This may indicate a form of engagement bias for people with acute LBP. Attentional bias was not consistent across outcome measures or word groups. Further research is needed to investigate the potential role of attentional bias in the development of persistent pain.

PMID:34019753 | DOI:10.1515/sjpain-2020-0014

Andrology. 2021 May 21. doi: 10.1111/andr.13042. Online ahead of print.

ABSTRACT

INTRODUCTION: Our study analysed previous studies employing Positron Emission Tomography with co-registered Computer Tomography (PET/CT) in andrological patient evaluation and assessed the differences in 2-[¹⁸ F]F-fluoro-2′-deoxyglucose (FDG) uptake between 3 groups: healthy testes, benign and malignant testicular pathology.

METHODS: MEDLINE and EMBASE were systematically searched for studies involving FDG-PET/CT imaging of testes with results expressed as Mean Standardised Uptake Value (SUV_mean ). A one-way ANOVA was used to compare SUV_mean between 3 groups. All papers assessing andrological parameters were pooled to enable a comparison of fertility data.

RESULTS: Seventeen studies, including three relating to fertility diagnosis, with a total of 830 patients were included in the review. One-way ANOVA showed a statistical difference between mean values of tracer SUV_mean in healthy and malignant testes (Dif. = -2.77, 95%CI = -4.32 to 1.21, p<0.01) as well as benign and malignant (Dif. = -2.95, 95%CI = -4.33 to -1.21, p<0.01) but no difference between healthy and benign (Dif. = 0.19, 95%CI = -0.96 to 1.33, p = 0.90). There is some evidence to suggest FDG uptake and testicular volume are positively correlated to total sperm count, sperm concentration and sperm motility and that germ cells are likely to account for the majority of testicular FDG accumulation.

CONCLUSION: Our findings indicate that malignant testicular lesions demonstrate a significantly higher FDG uptake than benign testicular lesions or healthy testes. Some evidence also suggests that FDG-PET could inform on metabolic activity and thus spermatogenesis, however more studies are needed to determine whether FDG-PET could also be used to determine differences between normal and oligospermic testes. Further studies should focus on correlating both sex hormone serum levels and semen analysis results with imaging data. This article is protected by copyright. All rights reserved.

PMID:34019736 | DOI:10.1111/andr.13042

Public Health Nurs. 2021 May 21. doi: 10.1111/phn.12923. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the development, feasibility, and preliminary efficacy of a seven-module e-learning for enhancing cultural competence of public health workers.

DESIGN: The study was based on the framework of the new Medical Research Council; a mixed methods design was used.

SAMPLE: A four-week pilot cluster-randomized controlled trial was conducted with 39 public health workers and 74 migrants in South Korea. Feasibility and preliminary efficacy were assessed according to initiation, retention, adherence, usability, acceptability, individual and organizational cultural competence, and migrant trust and satisfaction. Quantitative data were collected at baseline, 4 weeks, and 12 weeks. Focus group interviews were conducted with eight public health workers at 12 weeks.

RESULTS: Initiation, retention, and adherence rates were high. Participants agreed on acceptability, but exhibited mixed results on usability. Participants were satisfied with “well-structured content,” “authentic case stories and videos,” “increased interest in migrant care,” and “opportunity for self-reflection.” However, “flawless and trouble-free system,” “screen design for easy navigation,” “instructor’s expertise,” and “more situational cases and videos” were desired. Statistically significant differences were observed for individual cultural competence, migrant trust, and satisfaction.

CONCLUSION: Generally, the intervention seems feasible and has preliminary efficacy, yet usability improvement is necessary for full-scale randomized controlled trials.

PMID:34019724 | DOI:10.1111/phn.12923

Neuromodulation. 2021 May 21. doi: 10.1111/ner.13454. Online ahead of print.

ABSTRACT

OBJECTIVES: We sought to evaluate whether the cutaneous silent period (CSP) could be an electrophysiological indicator reflective of the effects of therapy for Parkinson’s disease (PD), including anti-PD medications or deep brain stimulation (DBS).

MATERIAL AND METHODS: We recorded the CSP in 43 patients with PD prior to and following the administration of medication during a pre-DBS evaluation (30 cases) and the “on” and “off” states of subthalamic nucleus DBS (13 cases). The CSP was elicited from the abductor pollicis brevis muscle by an electrical stimulation of the index finger that was 2, 4, and 15 times stronger than the sensory threshold (ST). We measured changes in latencies, including the onset, duration, and end of CSP, and waveform scores from 0 to 3. The correlation between the CSP score and unified PD rating score part III (UPDRS-III) also was assessed.

RESULTS: The onset latency and duration of CSP were significantly different between high (15ST) and low-strength stimulations (2ST and 4ST). However, there were no significant latency changes (onset, duration, end of CSP) before and after receiving medication, or during the on and off state of the DBS. Anti-PD medications substantially increased the CSP waveform score only in the 4ST state. However, the waveform score significantly increased in all stimuli states during the DBS-on state. Both medication and the DBS-on state decreased the UPDRS-III. Nevertheless, there was no statistically significant correlation between the UPDRS-III and CSP waveform scores.

CONCLUSION: Different onset latencies and the duration of CSP between low- and high-strength stimuli support the hypotheses proposing two different reflex pathways. Despite being independent from the UPDRS-III, the CSP may be an electrophysiological indicator reflective of the changes in inhibitory activity to the spinal α-motoneuron in response to anti-PD medications and DBS.

PMID:34019718 | DOI:10.1111/ner.13454

Biopharm Drug Dispos. 2021 May 21. doi: 10.1002/bdd.2292. Online ahead of print.

ABSTRACT

Generic drug development is a complex process that involves development of formulation similar to Reference Listed Drug (RLD). Because of the complexity associated with generic drug development, many regulatory agencies have come up with various guidelines. Out of many guidelines, the Biopharmaceutics classification system (BCS) that was introduced in 1995 based on aqueous solubility and permeability helped many pharmaceutical scientists across the globe to utilize the tool for formulation development, waiver of in vivo studies. Later on in vitro guidelines based on dissolution and IVIVC were introduced by many regulatory agencies with an intent to reduce number of in vivo human testing thereby facilitating shorter development time and faster approvals and launch. Most recently understanding the importance in silico approaches such as PBPK modelling, regulatory agencies such as USFDA and EMA came up with modelling guidance documents. Even though consensus exists between guidance documents from various regulatory agencies, still there are many minor to major differences exists between these guidance documents that needs to be considered while submitting a generic drug application. This review aims to compare all the in vitro and in silico guidance documents from major regulatory agencies with emphasis on latest trends and technologies combined with regulatory acceptability with an intention to harmonize regulations. Guidance documents from major regulatory agencies such as USFDA, EMA, WHO, ICH and other emerging markets were compared. Similarities &differences among these guidance documents are critically reviewed to provide the reader a detailed overview of these guidance documents at one place. This article is protected by copyright. All rights reserved.

PMID:34019712 | DOI:10.1002/bdd.2292

J Neurosci Res. 2021 May 21. doi: 10.1002/jnr.24851. Online ahead of print.

ABSTRACT

Recent evidence indicates that both cardiovascular fitness and gross motor skill performance are related to enhanced neurocognitive functioning in children by influencing brain structure and functioning. This study investigates the role of white matter microstructure in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning in healthy children. In total 92 children (mean age 9.1 years, range 8.0-10.7) were included in this study. Cardiovascular fitness and gross motor skill performance were assessed using performance-based tests. Neurocognitive functioning was assessed using computerized tests (working memory, inhibition, interference control, information processing, and attention). Diffusion tensor imaging was used in combination with tract-based spatial statistics to assess white matter microstructure as defined by fractional anisotropy (FA), axial and radial diffusivity (AD, RD). The results revealed positive associations of both cardiovascular fitness and gross motor skills with neurocognitive functioning. Information processing and motor response inhibition were associated with FA in a cluster located in the corpus callosum. Within this cluster, higher cardiovascular fitness and better gross motor skills were both associated with greater FA, greater AD, and lower RD. No mediating role was found for FA in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning. The results indicate that cardiovascular fitness and gross motor skills are related to neurocognitive functioning as well as white matter microstructure in children. However, this study provides no evidence for a mediating role of white matter microstructure in these relationships.

PMID:34019710 | DOI:10.1002/jnr.24851

J Med Virol. 2021 May 21. doi: 10.1002/jmv.27097. Online ahead of print.

ABSTRACT

We aimed to find the most useful biomarker by examining the prognostic effect of neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platalet-lymphocyte ratio (PLR) and lymphocyte-C reactive protein ratio (LCR) in COVID-19 patients. 304 patients diagnosed with COVID-19 infection in our hospital within five months (April-August 2020) were examined. Laboratory values and demographic findings of the patients were analyzed retrospectively. 36 were diagnosed with severe cases. The ratio of NLR, LMR, PLR, and LCR of patients with severe and those non-severe clinic were statistically analyzed. The NLR and PLR ratios of those with severe clinic were significantly higher (p <0.001), the LCR rate was significantly lower (p <0.001), and there was no significant difference in the LMR rate (p = 0.199). When we examined other peripheral blood parameters, we found that CRP was high, lymphocyte and monocyte were low (p <0.001), but neutrophil (p = 0.416) and platelet (p = 0.998) were not statistically different between the groups. According to the results, routine blood values are abnormal in COVID-19 patients. NLR, PLR and LCR ratios can be used as more significant biomarkers than other values in predicting prognosis of patients. This article is protected by copyright. All rights reserved.

PMID:34019701 | DOI:10.1002/jmv.27097

Sleep. 2021 May 21:zsab133. doi: 10.1093/sleep/zsab133. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Delivery prior to full term affects 37% of US births, including ~400,000 preterm births (<37 weeks) and >1,000,000 early term births (37-38 weeks). Approximately 70% of cases of shortened gestation are spontaneous – without medically-indicated cause. Elucidation of modifiable behavioral factors would have considerable clinical impact.

METHODS: This study examined the role of depressive symptoms and sleep quality in predicting the odds of spontaneous shortened gestation among 317 women (135 Black, 182 White) who completed psychosocial assessment in mid-pregnancy.

RESULTS: Adjusting for key covariates, Black women had 1.89 times higher odds of spontaneous shortened gestation compared to White women (OR (95% CI) = 1.89 (1.01, 3.53), p=0.046). Women who reported only poor subjective sleep quality (PSQI > 6) or only elevated depressive symptoms (CES-D ≥ 16) exhibited no statistically significant differences in odds of spontaneous shortened gestation compared to those with neither risk factor. However, women with comorbid poor sleep and depressive symptoms exhibited markedly higher odds of spontaneous shortened gestation than those with neither risk factor [39.2% versus 15.7%, [OR (95% CI) = 2.69 (1.27, 5.70), p = 0.01]. A higher proportion of Black women met criteria for both risk factors (23% of Black women versus 11% of White women; p=0.004), with a lower proportion experiencing neither risk factor (40.7% of Black versus 64.3% of White women; p < 0.001).

CONCLUSIONS: Additive effects of poor subjective sleep quality and depressive symptoms were observed with markedly higher odds of spontaneous shortened gestation among women with both risk factors. Racial inequities in rates of comorbid exposure corresponded with inequities in shortened gestation. Future empirical studies and intervention efforts should consider the interactive effects of these commonly co-morbid exposures.

PMID:34019675 | DOI:10.1093/sleep/zsab133

Nucleic Acids Res. 2021 May 21:gkab340. doi: 10.1093/nar/gkab340. Online ahead of print.

ABSTRACT

RNA-RNA inter- and intramolecular interactions are fundamental for numerous biological processes. While there are reasonable approaches to map RNA secondary structures genome-wide, understanding how different RNAs interact to carry out their regulatory functions requires mapping of intermolecular base pairs. Recently, different strategies to detect RNA-RNA duplexes in living cells, so called direct duplex detection (DDD) methods, have been developed. Common to all is the Psoralen-mediated in vivo RNA crosslinking followed by RNA Proximity Ligation to join the two interacting RNA strands. Sequencing of the RNA via classical RNA-seq and subsequent specialised bioinformatic analyses the result in the prediction of inter- and intramolecular RNA-RNA interactions. Existing approaches adapt standard RNA-seq analysis pipelines, but often neglect inherent features of RNA-RNA interactions that are useful for filtering and statistical assessment. Here we present RNAnue, a general pipeline for the inference of RNA-RNA interactions from DDD experiments that takes into account hybridisation potential and statistical significance to improve prediction accuracy. We applied RNAnue to data from different DDD studies and compared our results to those of the original methods. This showed that RNAnue performs better in terms of quantity and quality of predictions.

PMID:34019662 | DOI:10.1093/nar/gkab340

Transl Vis Sci Technol. 2021 May 3;10(6):28. doi: 10.1167/tvst.10.6.28.

ABSTRACT

PURPOSE: To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans.

METHODS: Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch’s membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength.

RESULTS: The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20).

CONCLUSIONS: Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness.

TRANSLATIONAL RELEVANCE: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

PMID:34019635 | DOI:10.1167/tvst.10.6.28