Nevin Manimala

J Ethnopharmacol. 2023 Sep 2:117120. doi: 10.1016/j.jep.2023.117120. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological relevance: Dried and mature seeds of Vaccaria segetalis (Neck.) Garcke ex Asch. (VS) are known for their therapeutic effects, as they stimulate blood circulation, promote menstruation and diuresis and eliminate gonorrhoea. However, due to its hard shell, the dissolution of its active ingredients is often improved by steaming and frying in clinical applications. Among the processed products, wine-steamed Vaccaria segetalis (WVS) is one of the commonly used ones. Numerous historical records have shown that wine steaming can enhance the efficacy of drugs to promote blood circulation and remove blood stasis. However, the differences in the efficacy of VS and WVS in promoting blood circulation and removing blood stasis have not been thoroughly studied, and the possible reasons for these differences have not been reported.

AIM OF THE STUDY: The objective of this study was to identify quality markers (Q-markers) that could differentiate the efficacy of promoting blood circulation and removing blood stasis of VS and WVS, which could serve as a basis for the rational application of VS and WVS in clinical settings.

MATERIALS AND METHODS: A pharmacodynamic comparison between the water extracts of VS and WVS was carried out based on a mouse acute blood stasis model (ABS) and thrombus zebrafish model. The potential bioactive substances of WVS were screened by investigating the correlation between common peaks identified for 10 batches of WVS by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and their rate of thrombosis inhibition in zebrafish. Furthermore, multivariate statistical analysis of chemical components between VS and WVS was conducted to speculate the Q-markers combined with the results of the bioactive components. Based on the efficacy verification of Q-markers, the content of Q-markers in 10 batches of WVS was evaluated.

RESULTS: The results of efficacy comparison assays demonstrated that the efficacy of WVS was more prominent than VS at the same dose. 5 components were screened as effective components of WVS for promoting blood circulation and removing blood stasis by correlation analysis. Furthermore, a total of 24 common ingredients were identified in VS and WVS extracts, and 9 of them showed increased dissolution rate after wine steaming, including 4 active ingredients, Hypaphorine, Vaccarin, Saponarin, and Isovitexin-2″-O-arabinoside, which were screened out by correlation analysis. The monomer test suggested that these 4 components could activate blood circulation and remove blood stasis in a dose-dependent manner. Consequently, Hypaphorine, Vaccarin, Saponarin, and Isovitexin-2″-O-arabinoside were selected as Q-markers to distinguish between VS and WVS. The content determination showed that the total contents of 4 Q-markers of WVS from 10 batches with different origins ranged from 0.478% to 0.716%.

CONCLUSIONS: This study compared the efficacy of VS and WVS in promoting blood circulation and resolving stasis and revealed Q-markers that reflected the difference in efficacy between them for the first time, which laid the foundation for establishing quality standards for WVS.

PMID:37666377 | DOI:10.1016/j.jep.2023.117120

J Pain Symptom Manage. 2023 Sep 2:S0885-3924(23)00661-9. doi: 10.1016/j.jpainsymman.2023.08.020. Online ahead of print.

ABSTRACT

The CONSORT guideline defines a pilot trial as a small-scale version of a desired future efficacy trial that is intended to answer the key questions of whether and how a larger study should be done. For example, a pilot trial might evaluate willingness of participants to undergo randomization or test different instruments for measuring an outcome. In addition to assessing feasibility of a future study, many investigators use pilot trials to obtain preliminary estimates of efficacy that might be used to gauge the promise of a new intervention, or to use in grant proposals to justify research funding. However, pilot trials do not provide reliable information about intervention efficacy due to the statistical phenomenon called sampling variability. In this brief tutorial we use computer simulation to demonstrate the influence of sampling variability on estimates of efficacy from pilot trials. The simulations show how pilot trial results can lead to erroneous decision making using a survival endpoint in a parallel arm clinical trial as an example. No background in programming or mathematics is required to understand the example. However, R code is provided for interested readers.

PMID:37666368 | DOI:10.1016/j.jpainsymman.2023.08.020

Neurotoxicol Teratol. 2023 Sep 2:107292. doi: 10.1016/j.ntt.2023.107292. Online ahead of print.

ABSTRACT

AIM: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD).

METHODS: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day.

RESULTS: Individuals with a diagnosis FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum conditions (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services.

INTERPRETATION: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

PMID:37666366 | DOI:10.1016/j.ntt.2023.107292

Exp Hematol. 2023 Sep 2:S0301-472X(23)01675-2. doi: 10.1016/j.exphem.2023.08.007. Online ahead of print.

ABSTRACT

Autologous hematopoietic stem cell transplantation (auto-SCT) is the recommended treatment for responding multiple myeloma (MM) patients. However, we do not know the risk factors influencing long-term survival without progression after auto-SCT. Therefore, this prospective study aimed to investigate the influence of transplanted cells with cluster of differentiation (CD)184+ expression, CD26+ lymphocyte and monocyte, and reconstitution lymphocytes CD3+ on overall survival (OS) and progression-free survival (PFS) after auto-SCT in MM. Forty-eight patients with MM underwent auto-SCT at our center from 2011 to 2013. The numbers of CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes were measured in the harvested material. In addition, the number of lymphocyte subpopulations (CD3+ lymphocytes, helpers, suppressors, natural killer (NK), cytotoxic NK, and B lymphocytes) was measured in peripheral blood during regeneration after auto-SCT. Flow cytometry was performed in both cases. The median OS was 92 months. Our analysis revealed a statistically significant effect of the number of transplanted CD184+ cells on OS and a statistically significant correlation between PFS and the number of transplanted CD184+ cells and reconstitution of CD3+ lymphocytes. In conclusion, our study showed that the increasing numbers of transplanted CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes augmented the risk of death.

PMID:37666354 | DOI:10.1016/j.exphem.2023.08.007

Ann Thorac Surg. 2023 Sep 2:S0003-4975(23)00919-0. doi: 10.1016/j.athoracsur.2023.08.019. Online ahead of print.

ABSTRACT

BACKGROUND: In 2016, we reported promising mid-term outcomes of the bicuspid pulmonary valve replacement using 0.1-mm polytetrafluoroethylene (PTFE) membrane. This follow-up study analyzes long-term outcomes and risk factors for reintervention and structural valve deterioration (SVD).

METHODS: We performed a retrospective review of the original 119 patients who underwent PTFE bicuspid pulmonary valve replacement. The median age was 16.9 years (range 0.4 to 57.1 years). Reintervention was defined as any surgical or percutaneous catheter procedure on the PTFE valve. SVD was defined as development of a peak pressure gradient ≥ 50 mmHg or ≥ moderate amount of pulmonary regurgitation on follow-up echocardiography.

RESULTS: The median follow-up duration was 9.5 years. The survival rate was 96.5% at 5 and 10 years, with 2 early and 2 late mortalities. Freedom from reintervention was 90.0% at 5 years and 63.3% at 10 years. Freedom from SVD was 92.8% at 5 years and 51.1% at 10 years, with regurgitation being the predominant mode (64.6%). Freedom from both reintervention and SVD at 5 and 10 years were 89.1% and 49.5%, respectively. Multivariable analysis identified smaller valve diameter (hazard ratio 0.82, p<0.001) and more than trivial pulmonary regurgitation at discharge (hazard ratio 5.81, p<0.001) as risk factors for reintervention or SVD.

CONCLUSIONS: Long-term results of the PTFE bicuspid PVR were acceptable. However, improvements may be needed to reduce technical error and improve durability. Smaller valve diameter and more than trivial pulmonary regurgitation at discharge were risk factors for reintervention or SVD, warranting careful follow-up for timely reintervention.

PMID:37666352 | DOI:10.1016/j.athoracsur.2023.08.019

Orthop Traumatol Surg Res. 2023 Sep 2:103674. doi: 10.1016/j.otsr.2023.103674. Online ahead of print.

ABSTRACT

INTRODUCTION: Proximal femoral osteotomy is an important step in the management of paralytic hip dislocation. Fixation by the angled plate is demanding and carries the risk of many complications. In this study, we made certain modifications for the angled plate. Does this plate provide a stable fixation for proximal femoral varus osteotomy? The main objective of this study was to assess the results of the modified plate in fixation of proximal femoral varus osteotomy in patients with neuromuscular hip dislocation.

HYPOTHESIS: This new system would offer significant advantages over the existing systems in terms of easy application and stable fixation.

MATERIAL AND METHODS: Twenty patients with paralytic hip dislocation were included in this study. The ages ranged from 5 to 15 years with a mean of 8.88±2.92 years. There were 12 boys and 8 girls. Seventeen patients had cerebral palsy and 3 had meningocele disease. Pre-operative radiographs were done, and the migration percentage (MP), acetabular index (AI), and neck-shaft angle (NSA) were measured. All patients were treated with open reduction, pelvic osteotomy, and proximal femoral varus osteotomy. The femoral osteotomy was fixed by the modified angled plate in all cases.

RESULTS: The osteotomy sites united in all patients and the mean time of union was 2.9±0.65 months. The acetabular index, migration percentage, and neck-shaft angle were reduced postoperatively. This reduction was statistically significant. The hips remained stable throughout the period of follow-up in all patients. No cases were complicated by nonunion or implant failure.

CONCLUSION: The modified angled plate (canulated interlocking blade plate 90°) is a good method for the fixation of proximal femoral varus osteotomy in the management of neuromuscular hip dislocation. It provides a stable fixation.

LEVEL OF EVIDENCE: IV; case series.

PMID:37666326 | DOI:10.1016/j.otsr.2023.103674

Environ Res. 2023 Sep 2:117070. doi: 10.1016/j.envres.2023.117070. Online ahead of print.

ABSTRACT

Many epidemiologic studies concerned with acute exposure to ambient PM_2.5 have reported positive associations for respiratory disease hospitalization. However, few studies have investigated this relationship in Kuwait and extrapolating results from other regions may involve considerable uncertainty due to variations in concentration levels, particle sources and composition, and population characteristics. Local studies can provide evidence for strategies to reduce risks from episodic exposures to high levels of ambient PM_2.5 and generating hypotheses for evaluating health risks from chronic exposures. Therefore, using speciated PM_2.5 data from local samplers, we analyzed the impact of daily total and source-specific PM_2.5 exposure on respiratory hospitalizations in Kuwait using a case-crossover design with conditional quasi-Poisson regression. Total and source-specific ambient PM_2.5 were modeled using 0-5-day cumulative distributed lags. For total PM_2.5, we observed a 0.16% (95% confidence interval [CI] = 0.05, 0.27%) increase in risk for respiratory hospitalization per 1 μg/m³ increase in concentration. Of the source factors assessed, dust demonstrated a statistically significant increase in risk (0.16%, 95% CI = 0.04, 0.29%), and the central estimate for regional PM_2.5 was positive (0.11%) but not statistically significant (95% CI = -0.11, 0.33%). No effect was observed from traffic emissions and ‘other’ source factors. When hospitalizations were stratified by sex, nationality, and age, we found that female, Kuwaiti national, and adult groups had higher effect estimates. These results suggest that exposure to ambient PM_2.5 is harmful in Kuwait and provide some evidence of differential toxicity and effect modification depending on the PM_2.5 source and population affected.

PMID:37666316 | DOI:10.1016/j.envres.2023.117070

World Neurosurg. 2023 Sep 2:S1878-8750(23)01234-2. doi: 10.1016/j.wneu.2023.08.121. Online ahead of print.

ABSTRACT

Knowing the motor branches and variations of the musculocutaneous nerve to the muscles along its course will facilitate the treatment of flexor spasticity and supracondylar fractures of the humerus in order to minimize nerve lesion. In fetal cadavers, the purpose of our study was to determine the number and course of the formation variations and motor branches of the musculocutaneous nerve. The significance of studying fetal nerve variations is due to injury to the brachial plexus roots during birth. Our study was conducted using the anatomical dissection technique on 102 upper limbs from 51 fetuses ages ranged from 17 to 40 weeks. Throughout its course, the variations and motor branches of the musculocutaneous nerve were analyzed. In 13.7% of cases, the musculocutaneous nerve did not piercing the coracobrachialis. The musculocutaneous nerve gave the muscles 1-3 motor branches. Additionally, motor branches terminated with 1-7 fringes. The biceps brachii motor branches of the musculocutaneous nerve were typed. Accordingly, 15.6% were type 1A, 3.9% were type 1B, 35.4% were type 1C, and 19.6% were type 1D. It was determined that 23.5% of the extremities were type 2 and that 1.9% were type 3. The distance between the musculocutaneous nerve’s motor branches and the acromion was proportional to the arm’s length. There were no statistically significant differences between the sides and genders for any measurement. Our study’s findings will aid in the diagnosis and treatment of pediatrics, orthopedics, surgical sciences, and radiology conditions. It reduces the risk of iatrogenic injury and postoperative complications. We also believe that our research will serve as a resource for anatomists and other scientists.

PMID:37666297 | DOI:10.1016/j.wneu.2023.08.121

Mutat Res Rev Mutat Res. 2023 Sep 2:108468. doi: 10.1016/j.mrrev.2023.108468. Online ahead of print.

ABSTRACT

There is concern about human exposure to nanoplastics from intentional use or degradation of plastics in the environment. This review assesses genotoxic effects of nanoplastics, defined as particles with a primary size of less than 1000nm. The majority of results on genotoxicity come from studies on polystyrene (PS) particles in mammalian cell cultures. Most studies have measured DNA strand breaks (standard comet assay), oxidatively damaged DNA (Fpg-modified comet assay) and micronuclei. Twenty-nine out of 60 results have shown statistically significant genotoxic effects by PS exposure in cell cultures. A statistical analysis indicates that especially modified PS particles are genotoxic (odds ratio = 8.6, 95% CI: 1.6, 46) and immune cells seems to be more sensitive to genotoxicity than other cell types such as epithelial cells (odds ratio = 8.0, 95% CI: 1.6, 39). On the contrary, there is not a clear association between statistically significant effects in genotoxicity tests and the primary size of PS particles, (i.e. smaller versus larger than 100nm) or between the type of genotoxic endpoint (i.e. repairable versus permanent DNA lesions). Three studies of PS particle exposure in animals have shown increased level of DNA strand breaks in leukocytes and prefrontal cortex cells. Nanoplastics from polyethylene, propylene, polyvinyl chloride and polyethylene terephthalate have been investigated in very few studies and it is currently not possible to draw conclusion about their genotoxic hazard. In summary, there is some evidence suggesting that PS particles may be genotoxic in mammalian cells.

PMID:37666295 | DOI:10.1016/j.mrrev.2023.108468

Nutr Res. 2023 Aug 4;118:137-145. doi: 10.1016/j.nutres.2023.07.011. Online ahead of print.

ABSTRACT

A diet high in quality is essential for prevention of chronic diseases. Specific healthy eating behaviors may modulate dietary intake. However, these behaviors have been seldomly studied, particularly in Puerto Rico (PR), a population with documented poor dietary quality and high burden of chronic diseases. This study aimed to document self-reported engagement in eating behaviors and examine their associations with intake of nutrients and diet quality. We hypothesized that greater engagement in healthy eating behavior would be associated with greater diet quality. This cross-sectional analysis used data from the PRADLAD study (adults aged 30-75 years residing in the San Juan, PR, area [n = 234]). Frequency (never, sometimes, often, always) of habitual eating behaviors was measured. Dietary intake was assessed with a food frequency questionnaire. Diet quality was measured with the Alternate Healthy Eating Index-2010. Statistical analyses included adjusted linear models. The most common behavior was “controlling intake of salt” (51.7%). Engaging “always” (vs. less frequently) in making healthier meals, reading nutrition facts labels, searching media for healthy eating information, counting calories, buying organic foods, eating a vegetarian diet, and controlling intake of salt, fat, carbohydrates/sugar, and portions were associated with higher Alternate Healthy Eating Index-2010 scores (P < .05). Controlling intakes of fats, carbohydrates/sugars, and portions “always” was associated with lower intakes of trans fats, added sugars, and total food (g), respectively (P < .05). Engagement in eating a vegetarian diet “always” was associated with higher intake of plant-based protein (P < .05). In conclusion, adults following several habitual eating behaviors had greater diet quality and a lower amount of unfavorable nutrients. Encouraging adherence to these behaviors may contribute to healthier dietary intake.

PMID:37666009 | DOI:10.1016/j.nutres.2023.07.011