Notes

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Next, phloretin repressed the secretion of proteases and phospholipases via reducing the expression of protease-encoding genes secreted aspartyl proteases (SAP)1 and SAP2, as well as phospholipase B1. Subsequently, the in vivo antifungal activity of phloretin was testified by the reverse of the enhanced lesion severity, inflammatory infiltration, and the increased colony-forming unit counts caused by C. albicans of tongue tissues in oral candidiasis mice. In conclusion, phloretin suppressed the pathogenicity and virulence factors against C. albicans both in vivo and in vitro.Clinical relevance Considering the significant relationship between opioid abuse and some accommodative and convergence disorders, opioid use should be considered in the differential diagnosis and will directly affect the management plan.Background To determine the prevalence of accommodative and convergence anomalies and their related factors in a population of male young adults with opioid use disorder (OUD).Methods This cross-sectional study was conducted using a convenience sampling method in 2019. The study sample included male young adults with OUD who had been referred to a specialised drug-dependence rehabilitation centre in Mashhad, Iran. The diagnosis of OUD was made by a psychologist based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. All patients underwent complete optometric examinations.Results Eighty male young adults with OUD were included in this study. The mean age of participants was 30.5 ± 3.9 years (age range 19 to 35 years). The prevalence of accommodative and convergence disorders was 33.75% (95% CI 23.55-45.19) and 25.00 (95% CI 15.99-35.94), respectively. Accommodative insufficiency (22.5%, 95% CI 13.91-33.21) had a higher prevalence than accommodative excess (3.75%, 95% CI 0.78-10.57) and accommodative infacility (7.50%, 95% CI 2.80-15.61). Convergence insufficiency (18.75%, 95% CI 10.89-29.03) had a higher prevalence compared to convergence excess (3.75%, 95% CI 0.78-10.57) and basic exophoria (2.50%, 95% CI 0.30-8.74). According to the multiple logistic regression, a significant inverse relationship was observed between pupil size with accommodative insufficiency (OR = 0.45), accommodative infacility (OR = 0.67), and convergence insufficiency (OR = 0.55).Conclusion The results of the present study showed a higher prevalence of some accommodative and convergence disorders in OUD patients compared to the prevalence reported in previous studies conducted on the normal populations with a similar age range.Purpose Adolescents with cerebral palsy may need a feeding tube due to feeding challenges, since nutritional intake and mealtimes may be negatively affected. The purpose of the study was to describe and better understand how one adolescent with cerebral palsy and her parents experienced mealtimes before and after a nasogastric and gastrostomy tube insertion and how the use of these feeding tubes was experienced in daily life.Methods Individual interviews were performed with one adolescent and each of her parents. In total, six interviews were conducted on two separate occasions. The qualitative approach known as Interpretive Description was used during the analysis.Results Four thematic patterns were identified within the data (i) struggling with nutritional intake, (ii) the paradox of using an aid, (iii) being different, and (iv) challenges of public mealtimes.Conclusions The results showed that four themes influenced daily mealtimes in adolescents with cerebral palsy and a gastrostomy tube. Nutritional intake and mealtimes may be difficult, which is why using a gastrostomy tube can be a relief. However, the gastrostomy tube can also pose a challenge and a paradox. Time of change and acceptance seems necessary in order to meet these challenges.Aristolochic acid (AA) are persistent soil pollutants in the agricultural fields of the Balkan Peninsula. Preparations containing aristolochic acid are widely used for anti-inflammatory, diuretic, etc. To study the hepatotoxicity of aristolochic acid, 80 healthy SD rats were selected and divided into 20 mg/kg- AA group, 4 mg/kg-AA group, and 2 mg/kg-AA group and blank group, 20 rats per group. Mainly tested the body weight, liver function, liver tissue oxidative stress and pathological changes of liver tissue in rats. The ALT and AST activities in the serum of the rats in the administration groups were increased compared with the blank group. The activity of MDA in the administration groups was higher than that in the blank group; the activities of SOD, T-AOC and GSH-PX were significantly lower than those in the blank group. HE tissue sections also found that the administration groups showed varying degrees of hepatocyte boundary blur, nuclear fragmentation, and fibrosis tendency. Transmission electron microscopy showed that the mitochondria of the rat liver became more and more severely damaged with the increase of dose. Compared with the blank group, the mRNA expression of Bax, Caspase-9 and Caspase-3 in the administration groups were determined, while the mRNA expression of the Bcl-2 was increased. And compared with the blank control group, the expression levels of apoptotic proteins caspase-9 and caspase-3 increased significantly in the 20 mg/kg-AA group. Aristolochic acid can induce liver injury in rats through oxidative stress pathway and mitochondrial apoptosis pathway.Both theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood fluke Schistosoma mansoni shows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence to Biomphalaria glabrata snail hosts, and determined four-week cercarial shedding profiles in F0 parents, F1 parents and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs (i.e. Quantitative Trait Loci). These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.The purpose of this study was to investigate muscle synergies (MS) during upper limb cycling motion across power levels (20, 40, 60, 80, 100, and 120 watts). The MS hypothesis is important to the understanding of modular control for human movements. In this study, we explore its importance in execution of phasic movements at various power levels. Electromyographic (EMG) signals were recorded from 7 upper limb muscles during cycling for 30s on a hand-cycle ergometer. A Non-Negative Matrix factorization (NNMF) algorithm was used to extract MS. Cosine similarity was used to compare the MS and cross-correlation was used to compare activation coefficients. We found that the number and structure of synergies were consistent across power levels while admitting modulation in their activation coefficients. A total of three shared MS explaining ≥95% of the variance accounted for (VAF) represented push and pull mechanism during cyclic motion.MicroRNAs (miRNAs) play a very important role in the development of acute myeloid leukemia (AML). This study focuses on the effects of miR-9 on the regulation of AML cells and their related signaling pathways. We found that the expression of miR-9 was significantly decreased in four AML cell lines (THP-1, HL-60, TF-1 and KG-1) compared with the human normal bone marrow cells (HS-5). Moreover, miR-9 overexpression inhibited HL-60 cell proliferation ability, and promoted apoptosis. However, interfering with miR-9 expression promoted the proliferation of HL-6 cells and inhibited apoptosis. Western blotting results subsequently showed that overexpression of miR-9 could elevate the expression of MAT1, LATS1, and LATS2 in HL-60 cells, and inhibit the expression of YAP, while the interference with miR-9 had the opposite result. Taken together, miR-9 may act as a tumor suppressor by activating the Hippo/YAP signaling pathway of AML cells, which in this way supply ideas for the clinical remedy of AML patients.The tumor immune microenvironment plays an important role in head and neck squamous cell carcinoma (HNSCC). Reliable prognostic signatures able to accurately predict the immune landscape and survival rate of HNSCC patients are crucial to ensure an individualized/effective treatment. Here, we used HNSCC transcriptomic and clinical data retrieved from The Cancer Genome Atlas and identified differentially expressed immune-related long non-coding RNAs (DEirlncRNAs). DEirlncRNA pairs were recognized using univariate analysis. Cox and Lasso regression analyses were used to determine the association between DEirlncRNA pairs and the patients' overall survival and build the prediction model. Receiver operating characteristic curves and Kaplan-Meier survival curves were used to validate the prediction model. We then reevaluated the model based on the clinical factors, tumor-infiltrating immune cells, chemotherapeutic efficacy, and immunosuppression biomarkers. We built a risk score model based on 18 DEirlncRNA pairs, closely related to the overall survival of patients (hazard ratio 1.376; 95% confidence interval 1.302-1.453; P less then 0.0001). Compared with two recently published lncRNA signatures, our DEirlncRNA pair signature had a higher area under the curve, indicating better prognostic performance. Additionally, the signature score positively correlated with aggressive HNSCC outcomes (low immunity score, significantly reduced CD8 + T cell infiltration, and low expression of immunosuppression biomarkers). However, high-risk patients might have high chemosensitivity. Overall, the lncRNAs signature established here shows promising clinical prediction and the effective disclosure of the tumor immune microenvironment in HNSCC patients; therefore, such signature might help distinguish patients that could benefit from immunotherapy.Opioid use and misuse are a widespread problem across the United States. Identifying and targeting social determinants of opioid use may help to identify predictive factors to influence intervention and policy. The purpose of this study was to identify social determinants of opioid use frequency among patients seeking primary care in rural Alabama healthcare facilities. This survey-based study focused on a patient population located in rural west Alabama surveyed for a screening, brief intervention, and referral to treatment program. The screening tool contained demographic information and questions regarding the social determinants of health and opioid use, among others. Adjusted incidence rate ratios (IRRs) for the relationship between social determinants of health and opioid use frequency (in days/month) were estimated in Poisson regression models. Eleven percent of the population self-reported opioid use in the past 30 days. Three social determinants of health measured (level of education, housing stability, and employment status) were identified as having a significant association with the frequency of opioid use. Targeting certain social determinants of health may allow for further predictive interventions to mitigate opioid misuse and potential fatality or mortality.
A decrease in weight velocity and feeding difficulties in infants may be caused by an inadequate caloric intake and underlying medical conditions.

By focusing on four clinical cases, this article illustrates the temporary use of a special infant formula in orally-fed and enterally-fed infants with unsatisfactory weight gain and special medical conditions such as gastrointestinal and neurological disorders. The formula was a nutritionally complete hypercaloric infant formula containing partially hydrolyzed whey protein. It was used after full consideration of all feeding options including breastfeeding.

Implementing appropriate feeding behaviors, adapted to age and potential comorbidities, is an essential prerequisite for therapeutic management. The use of a nutritionally complete hypercaloric infant formula can be helpful to manage unsatisfactory weight gain and feeding difficulties in infants.
Implementing appropriate feeding behaviors, adapted to age and potential comorbidities, is an essential prerequisite for therapeutic management. The use of a nutritionally complete hypercaloric infant formula can be helpful to manage unsatisfactory weight gain and feeding difficulties in infants.The aim of this study was to identify hub genes closely related to the pathogenesis and prognosis of thyroid carcinoma (THCA) by integrated bioinformatics analysis. In this study, through differential gene expression analysis, 1916 and 665 differentially expressed genes (DEGs) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, and 7 and 11 co-expressed modules were identified from the TCGA-THCA and GSE153659 datasets, respectively, by weighted gene co-expression network analysis. We identified 162 overlapping genes between the DEGs and co-expression module genes as candidate hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the 162 overlapping DEGs identified significant functions and pathways of THCA, such as thyroid hormone generation and metabolic process. A protein-protein interaction (PPI) analysis detected the top 10 hub genes (QSOX1, WFS1, EVA1A, FSTL3, CHRDL1, FABP4, PRDM16, PPARGC1A, PPARG, COL23A1). Finally, survival analysis, clinical correlation analysis, and protein abundance validation confirmed that 3 of the 10 hub genes were associated with survival prognosis of patients with THCA, and 8 of them were associated with the clinical stages of THCA. In summary, we identified hub genes and key modules that were closely related to THCA, and validated these genes by survival analysis, clinical correlation analysis, and Human Protein Atlas image analysis. Our results provide important information that will help to elucidate the pathogenesis of THCA and identify novel candidate prognostic biomarkers and potential therapeutic targets.Along with the occurrence of cisplatin resistance, treatment on gastric cancer (GC) becomes difficult. Therefore, researches on new therapeutic methods to revert cisplatin resistance are becoming increasingly urgent. qRT-PCR was used to quantify the expression of miR-4486, JAK3 in SGC-7901 or SGC-7901/DDP cell lines. WB was utilized to analyze the expression of JAK3, STAT3 and p-STAT3 in SGC-7901/DDP cell lines. CCK-8 assay was used to determine the IC50 of cisplatin on both cell lines and cell viability of SGC-7901/DDP cell lines. The target relationship between miR-4486 and JAK3 was determined by luciferase assay. MiR-4486 expression on apoptosis of SGC-7901/DDP cell lines was determined by flow cytometry. qRT-PCR testified that miR-4486 decreased in SGC-7901/DDP cells, and the expression of miR-4486 mimic increased significantly compared with miR-4486 NC. By CCK-8 assay, the IC50 of cisplatin on both cell lines were 9 μg/mL and 81.3 μg/mL, and overexpression of miR-4486 decreased the viability of SGC-7901/DDP cells. Compared with DDP group, the expression of miR-4486 accelerated SGC-7901/DDP cells apoptosis. Dual-luciferase assay suggested that JAK3 was the target gene of miR-4486. qRT-PCR and WB proved that miR-4486/JAK3 axis inhibit the activation of JAK3/STAT3 pathway, and JAK3 overexpression can partly reverse this. As shown by CCK-8 and flow cytometry, miR-4486 overexpression decreased viability and stimulated apoptosis of SGC-7901/DDP cells. However, JAK3 overexpression can also partly revert this. miR-4486 overexpression could decrease viability and improve apoptosis of SGC-7901/DDP cells to revert its cisplatin-resistance, and the mechanism may be related to JAK3/STAT3 signalling pathway.
An estimated 45% of concussions are reported to be related to motor vehicle collisions (MVC). However, limited research exists involving the treatment of MVC-related concussion, especially when combined with whiplash-associated disorders (WAD).Purpose The purpose of this case series is to examine the patient response to an irritability-based approach to the physiological, cervical, and vestibulo-ocular trajectories in patients with diagnosed concussion and WAD disorder following an MVC.Case Description Three patients clinically diagnosed by a neurologist with WAD and concussion following a rear-end MVC were evaluated and treated in an outpatient physical therapy setting. Each individual was progressed through an irritability-based treatment approach based on individual symptom presentation.Outcomes Following therapy, 2 of 3 patients reported full resolution of subjective symptoms with a negative Vestibular Oculo-motor Screening All patients exceeded their predicted goals based on Focus on Therapeutic Outcomes score.

This case series demonstrated successful treatment of all three individuals with concussion and concurrent WAD. Two of three individuals demonstrated full resolution of subjective symptoms and objective impairments at the end of treatment. Further research is warranted into the effectiveness of a multi-factorial approach to address the highly variable symptom profile of individuals with concussion and WAD.
This case series demonstrated successful treatment of all three individuals with concussion and concurrent WAD. Two of three individuals demonstrated full resolution of subjective symptoms and objective impairments at the end of treatment. Further research is warranted into the effectiveness of a multi-factorial approach to address the highly variable symptom profile of individuals with concussion and WAD.Hair and/or nail analyses are sometimes used in biomonitoring studies due to the convenience of sample collection, storage, and transport, as well as the potential to assess past exposures to toxic metals, such as lead (Pb). However, the validity of Pb measurements in these keratinized matrices as biomarkers of absorbed dose remains unclear. The aim of this study was to examine the uptake of Pb into horns harvested postmortem from 11 goats that received a cumulative oral dose of up to 151 g Pb acetate over a period of 1-11 years as part of a long-term blood Pb proficiency testing program. Uptake of Pb into keratinized horn was compared to the corresponding underlying bony horn core, which, as part of the bone compartment, provided a measure of absorbed Pb dose. Two complementary analytical techniques were used to assess Pb X-Ray Fluorescence (XRF) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Detectable amounts of Pb were found in all keratinized horn samples (0.45-6.6 µg/g) and in all but one bony core sample (1.4-68 µg/g). In both bony core and keratinized horn samples, Pb accumulation increased with dose over a low-to-moderate cumulative-dose interval, consistent with previous observations, but plateaued at higher doses. Significant associations were observed between Pb in keratinized horn and bony core samples particularly with XRF measurements, which represent the surface bone compartment. These findings provide evidence that Pb is excreted in keratinized tissues but reflects only a small fraction of the absorbed Pb dose, likely transferred from underlying bone tissue.Introduction While sorafenib monotherapy represented the mainstay of medical treatment for advanced hepatocellular carcinoma (HCC) patients for more than a decade, novel agents and combination therapies have recently produced unprecedented paradigm shifts. The combination of lenvatinib plus pembrolizumab is now being evaluated as a front-line treatment in advanced HCC patients; early phase clinical trials have already reported promising results.Areas covered This paper reviews the combination of lenvatinib plus pembrolizumab for the treatment of advanced HCC. The preclinical rationale and completed and ongoing trials are examined and later, the authors reflect on biomarkers of predictive of response to immune-based combinations and future treatment decision-making on the basis of tolerability and clinical benefits provided by these novel therapeutics. A literature search was conducted in April 2021 of Pubmed/Medline, Cochrane library and Scopus databases; moreover, abstracts of international cancer meetings were reviewed.Expert opinion The landscape of new agents and combinations continues to expand. Recently, immune-based combinations have reported important results in advanced HCC, as witnessed by the landmark IMbrave150 trial. Based on the promising results of early phase clinical trials, lenvatinib plus pembrolizumab has the potential to represent a novel treatment option in this setting.Mesh repair of pelvic organ prolapse (POP) is complicated, causing erosions, postoperative pain and surgical failure. We hypothesised that reducing the mesh size and fixating it would result in significant cure rates and reduce complication rates. Here, we present the effectiveness of mini mesh implants in POP reconstruction. Sixty women who underwent repair of stage III and IV apical prolapse with cystocele or rectocele using skeletonised mesh implant Seratom PA MR MN® were evaluated. Anatomical outcomes were assessed using modified POP-quantification (POP-Q) staging and functional outcomes were self-reported by patients - one and three months post-operatively. Apical support with anterior and/or posterior colporrhaphy was performed, resulting in 96.6% success rate. Follow-up conducted one and three months post-operatively revealed significant improvement on the modified POP-Q (p  less then  .001) and no complaints of dyspareunia. Para-vesicular fixation using a skeletonised mini mesh implant is feasible and effective in POP repair and has low surgical complication risk.Impact StatementWhat is already known on this subject? Mesh repair for pelvic organ prolapse (POP) is currently under scrutiny as it may result in erosions, postoperative pain, and surgical failure.What do the results of this study add? The use of an apical support with mini-mesh implants resulted in a 96.6% (58/60) success rate and excellent outcomes at 1- and 3-month follow-up.What are the implications of these findings for clinical practice and/or further research? Reconstruction using skeletonised and fixated mini-mesh implants may be safe and effective for POP treatment.
Defibrotide (DF) is a polyribonucleotide with antithrombotic, pro-fibrinolytic, and anti-inflammatory effects on endothelium. These effects and the established safety of DF present DF as a strong candidate to treat viral and post-infectious syndromes involving endothelial dysfunction.

We discuss DF and other therapeutic agents that have the potential to target endothelial components of pathogenesis in viral and post-infectious syndromes. We introduce defibrotide (DF), describe its mechanisms of action, and explore its established pleiotropic effects on the endothelium. We describe the established pathophysiology of Coronavirus Disease 2019 (COVID-19) and highlight the processes specific to COVID-19 potentially modulated by DF. We also present influenza A and viral hemorrhagic fevers, especially those caused by hantavirus, Ebola virus, and dengue virus, as viral syndromes in which DF might serve therapeutic benefit. Finally, we offer our opinion on novel treatment strategies targeting endothelial dysfunction in viral infections and their severe manifestations.

Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.
Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.
To explore independent risk factors for incomplete radiofrequency ablation (iRFA) of colorectal cancer liver metastases (CRLM) and evaluate adverse outcomes following iRFA.

Magnetic resonance imaging data of CRLM patients who received percutaneous RFA were randomized into training (70%) and validation set 1 (30%) data sets. An independent validation set 2 was derived from computed tomography scans. Uni- and multivariate analyses identified independent risk factors for iRFA. Area under the curve (AUC) values were used to evaluate the predictive model performance. Risk points were assigned to independent predictors, and iRFA was predicted according to the total risk score. Kaplan-Meier curves were used to assess new intrahepatic metastases (NIHM), unablated tumor progression, and overall survival (OS).

Multivariate regression determined as independent iRFA risk factors perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm. The AUC values of the model in the training set, validation set 1, and validation set 2 were 0.867, 0.772, and 0.820, respectively. The respective AUC values of the total risk score were 0.864, 0.768, and 0.817. During the 6-year follow-up, the cumulative OS was significantly shorter in the iRFA than in the complete RFA group, and NIHM (hazard ratio [HR] = 2.79; 95% confidence interval [CI] 1.725, 4.513) and unablated tumor progression (HR = 3.473; 95% CI 1.506, 8.007) were more severe.

Perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm were independent risk factors for iRFA. iRFA may be a potential predictor of NIHM, unablated tumor progression, and OS.
Perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm were independent risk factors for iRFA. iRFA may be a potential predictor of NIHM, unablated tumor progression, and OS.We sought to characterize gun and ammunition purchasing during the initial phase of the COVID-19 pandemic using a nationally representative sample of U.S. adults. We fielded a survey using NORC's Amerispeak Panel between 7 and 22 July 2020 (survey completion rate = 91.1%, N = 1337). We used survey-weighted data to calculate the proportion of adults who purchased a gun during this time period and types of guns and amount of ammunition purchased. Between March and mid-July 2020, 6% of adults purchased a gun and 9% bought ammunition. Of those purchasing a gun, 34% were first-time purchasers. Among those purchasing ammunition, 19% reported purchasing more than usual in response to the COVID-19 pandemic while 27% purchased less than usual. An estimated 6,451,163 adults bought guns for the first time between March and mid-July 2020. Increases in gun purchasing, particularly among first-time gun owners, could pose significant short- and long-term implications for public health.
There is a lot of evidence that connects blood type to several diseases, including the development of diabetes mellitus type 2. The evidence for an association between ABO blood groups and the possibility of developing gestational diabetes mellitus (GDM) is scant and inconclusive. We aimed to examine the link between ABO blood group types and GDM by the use of a large population-based cohort of pregnant women.

A retrospective population-based cohort study was conducted using data collected from January 2013 to December 2017 from the Emek Medical Center, Afula, Israel. All pregnant women who underwent the two-step screening and diagnosed with GDM and delivered at >24weeks were included. Women who had pre-gestational diabetes or whose pregnancies were terminated were excluded. The odds ratio (OR) were obtained through binary logistic regression analysis and the corresponding 95% confidence interval (CI) by the use of both the univariable and multivariable analysis.

Of all 16,067 women included in the study cohort, 1712 (10.7%) had GDM. The incidence of GDM was 11.0%, 10.8%, 10.6%, and 8.8% in blood group A, B, O, and AB, respectively. After adjusting for maternal age, parity, and number of fetuses, AB blood group was associated with reduced risk for developing GDM compared to the other blood groups (
 = .038; adjusted OR 0.79; 95% CI 0.64-0.99). There was no difference in Rhesus factor between GDM and controls.

Women with AB blood group have a lower risk for developing GDM compared to other blood group types.
Women with AB blood group have a lower risk for developing GDM compared to other blood group types.In this work, the first mutual prodrug of 5-fluorouracil and heme oxygenase1 inhibitor (5-FU/HO-1 hybrid) has been designed, synthesised, and evaluated for its in vitro chemical and enzymatic hydrolysis stability. Predicted in silico physicochemical properties of the newly synthesised hybrid (3) demonstrated a drug-like profile with suitable Absorption, Distribution, Metabolism, and Excretion (ADME) properties and low toxic liabilities. Preliminary cytotoxicity evaluation towards human prostate (DU145) and lung (A549) cancer cell lines demonstrated that 3 exerted a similar effect on cell viability to that produced by the reference drug 5-FU. Among the two tested cancer cell lines, the A549 cells were more susceptible for 3. Of note, hybrid 3 also had a significantly lower cytotoxic effect on healthy human lung epithelial cells (BEAS-2B) than 5-FU. Altogether our results served as an initial proof-of-concept to develop 5-FU/HO-1 mutual prodrugs as potential novel anticancer agents.We present the findings of a prospective cohort study in a single tertiary hospital to review the patient experience and economic benefit of ambulatory hysteroscopy (AH). Data were collected between May 2017 and February 2020. Patient satisfaction was measured with qualitative survey. Hospital level financial data were obtained over two financial years (2017/18 and 2018/19) to identify seasonal variation. The primary outcome was patient satisfaction and the secondary outcome was cost of AH compared to hysteroscopy under GA. Three hundred and twenty-nine patients underwent AH. Two hundred and ninety-eight responses (91%) were collected. Ninety-five percent of procedures were successful. Median pain score was five out of 10. Despite pain, 94% of patients would undergo AH again and 97% would recommend it. The average hospital cost for AH was $259 compared with $3098 for hysteroscopy under GA. These findings support AH as a safe, well-tolerated and economically viable alternative to hysteroscopy under GA.Impact StatementWhat is already known on this subject? Hysteroscopy is traditionally performed in an operating theatre under general anaesthesia (GA). Technological advancements allow for the procedure to be performed in an outpatient setting. Despite advantages of ambulatory hysteroscopy (AH), GA hysteroscopy is still the predominant intervention in Australia.What the results of this study add? Patient satisfaction in AH was assessed. The median pain score was five out of 10. Despite pain, 94% of patients would undergo AH again and 97% would recommend it.What the implications are of these findings for clinical practice and/or further research? AH is a well-tolerated alternative to hysteroscopy under GA with significant cost benefits to the hospital and high patient satisfaction. Further research should focus on direct comparison of the two procedure approaches using randomised controlled trials.
We aimed to investigate the association of advanced maternal age with intrapartum cesarean delivery and to assess its risk factors and perinatal outcomes.

A retrospective cohort study of all women with singleton pregnancies who attempted a trial of labor (≥24 + 0 weeks of gestation) in a single center (2011-2017). The study population was stratified by parity (nulliparous or multiparous) and further sub-categorized into three cohorts (1) women <35 years at birth (reference group), (2) women aged 35-40 years, and (3) women >40 years. Labor and delivery characteristics and neonatal outcomes were compared.

Overall, 55,089 women were included 39, 192 (71.1%) were under 35 years old, 15,90712,892 (28.923.4%) were 35-40 y and 3,015 (5.5%) were >40 y. For nulliparas, the rate of intrapartum Cesarean deliveries increased with maternal age and approached 25.3% in those >40 y as compared to 8.9% for those <35 y. The positive association between Cesarean section rates and maternal age extends beyond nulliparas and is also seen in multiparas, although to a smaller degree. After adjusting for confounders, maternal age was significantly and independently associated with intrapartum cesarean delivery in a dose-dependent manner in nulliparous women, [adjusted Odd Ratio (aOR) 1.56 (95% Confidence Interval (CI) 1.39-1.76) and 2.53 (2.07-3.09)] among women aged 35-40 y and >40 y, respectively. Maternal age was not significantly associated with adverse neonatal outcome.

Advanced maternal age is an independent risk factor for intrapartum Cesarean delivery. Yet, the majority of older gravidae who attempt a trial of labor, even if nulliparous, deliver vaginally without an increase in adverse neonatal outcome.
Advanced maternal age is an independent risk factor for intrapartum Cesarean delivery. Yet, the majority of older gravidae who attempt a trial of labor, even if nulliparous, deliver vaginally without an increase in adverse neonatal outcome.We report a novel frameshift β-thalassemia (β-thal) mutation due to a two-nucleotide deletion at codon 118 of the β-globin gene (HBB c.356_357delTT) in a 4-year-old Iraqi Kurd female presenting as transfusion-dependent β-thal. This frameshift mutation, unlike many others involving the third exon, behaved as a recessive β0 defect and not as dominant β-thal mutation.Introduction The treatment of unresectable hepatocellular carcinoma (HCC) has radically changed after the approval of the combination of atezolizumab plus bevacizumab as first-line treatment. A strong preclinical rationale exists to support the combination of bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody (mAb), and atezolizumab, an anti-programmed death ligand 1 mAb. The efficacy of the combination was first assessed in the phase Ib GO30140 study, and the combination was then proven superior to the prior standard of care, sorafenib, in the phase III IMbrave150 trial.Areas covered This article focuses on the mechanism of action of atezolizumab and bevacizumab, their synergistic action, and the two clinical trials leading to approval. We also collected the body of post-hoc analyses and meta-analyses to help guide the decision-making process in terms of patient selection and subsequent treatments.Expert opinion Atezolizumab plus bevacizumab are the current standard of care for first-line treatment of unresectable or metastatic HCC and treatment-naïve patient should be treated with the combination, unless contraindications to the drugs. Since all the available agents for further lines of treatment have been approved for sorafenib-pretreated patients, prospective trials, post-hoc analyses, and real-world data assessing valid treatment sequencing are strongly needed.Nature products have been extensively used in the discovery and development of new drugs, as the most important source of drugs. The triazole ring is one of main pharmacophore of the nitrogen-containing heterocycles. Thus, a new class of triazole-containing natural product conjugates has been synthesised. These compounds reportedly exert anticancer, anti-inflammatory, antimicrobial, antiparasitic, antiviral, antioxidant, anti-Alzheimer, and enzyme inhibitory effects. This review summarises the research progress of triazole-containing natural product derivatives involved in medicinal chemistry in the past six years. This review provides insights and perspectives that will help scientists in the fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology.
Among low-risk pregnancies, we ascertained the association between 10-minute Apgar score and adverse outcomes of newborn infants.

We conducted a retrospective cohort study using the U.S. vital statistics datasets (2011-2018), which included live births from low-risk women with non-anomalous singleton gestations who delivered at 37-41 weeks. When a newborn infant had an abnormal 5-minute Apgar score (0-5), a 10-minute Apgar score was documented in the birth certificate. Apgar score at 10 min was categorized as low (0-3), moderate (4-6), and normal (7-10). The primary outcome was composite neonatal adverse outcome. The secondary outcomes were individual neonatal adverse outcomes and infant mortality. Multivariable Poisson regression analyses were used to estimate the association between 10-minute Apgar score and adverse outcomes (using adjusted relative risk [aRR] and 95% confidence intervals [CI]).

Of 31.5 million live births delivered (2011-2018), 111,163 (0.4%) met inclusion criteria; of them, 74.2%, 20.7%, and 5.1% had normal, moderate, and low 10-minute Apgar scores, respectively. The overall composite neonatal adverse outcome was 100.6 per 1,000 live births and the risk was significantly higher among those with a moderate (aRR 3.19; 95% CI 3.06-3.31) or low 10-minute Apgar score (aRR 6.62; 95% CI 6.34-6.91) than with a normal 10-minute Apgar score. Infant mortality also showed a similar pattern. Newborn infants with improved Apgar scores from 5 to 10 min were associated with lower risks of the composite neonatal adverse outcome, as well as infant mortality, than those with scores that remained stable.

Among low-risk pregnancies, newborn infants with a lower 10-minute Apgar score were associated with a higher risk of adverse outcomes.
Among low-risk pregnancies, newborn infants with a lower 10-minute Apgar score were associated with a higher risk of adverse outcomes.
Recent years have registered the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combination therapies with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Immuno-TKI combinations have been suggested to improve clinical outcomes but may also result in increased toxicity, including gastrointestinal (GI) adverse events.

Herein, we performed a meta-analysis aimed at comparing the risk of certain GI toxicities in mRCC patients treated with immuno-TKI combinations versus sunitinib monotherapy. Overall, four phase III trials (KEYNOTE-426, JAVELIN Renal 101, CheckMate 9ER, CLEAR) involving 3059 mRCC patients were available.

The meta-analysis suggested an increased risk of all-grade diarrhea, grade 3-4 diarrhea and grade 3-4 decreased appetite in patients treated with immuno-TKI combinations. Conversely, an apparently higher risk of all-grade nausea was observed in the sunitinib group.

The meta-analysis suggested that immuno-TKI combinations are associated with higher risk of GI toxicities compared with sunitinib. Beyond the efficacy of immuno-TKI combinations in mRCC patients, careful consideration should be given to treatment-related adverse events, including GI toxicities. Early recognition and treatment are critical to maximize recovery.
The meta-analysis suggested that immuno-TKI combinations are associated with higher risk of GI toxicities compared with sunitinib. Beyond the efficacy of immuno-TKI combinations in mRCC patients, careful consideration should be given to treatment-related adverse events, including GI toxicities. Early recognition and treatment are critical to maximize recovery.Five pathways involving different ring structures led to generation of fourteen thienylbenzamides (7-20) which display the structure-activity relationships of class I HDAC inhibitors. All the synthesised compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound. Compounds 8 and 16 inhibit HCT116 cells by activation of the apoptosis pathway.
Cornea injury of sulfur mustard (SM) is considered as the most devastating injuries to the eye. This study aimed to evaluate the single and combined effects of
-acetyl cysteine (NAC) and doxycycline on the inflammatory pathway and cornea neovascularization (CNV) in the rat model of SM-injured cornea.

The right cornea of male Sprague-Dawley rats was subjected to 2-chloroethyl-ethyl sulfide (CEES). Rats were topically treated with a single and combined of 0.5% NAC and 12.5 μg/ml doxycycline and examined at 3rd, 15th, and 21st days. The activity of three antioxidant enzymes was analyzed in the cornea of different groups. Real-time PCR was performed to measure gene expression of inflammatory factors (
) and angiogenesis factors (
) in the cornea lysates. The histological and opacity assessments were also carried out.

The activity of antioxidant enzymes significantly declined 3 days after the CEES damage. NAC eye drop recovered the enzyme activity on the 21st day of treatment (
-value < .05). The expression of
and
genes significantly increased after CEES cornea exposure, while NAC declined their expression on the 7th and 21st days. The CNV score and angiogenesis factor expression were decreased in the long term by single and combined treatments (
-value < .05), but the infiltration of inflammatory cells was not completely amended.

NAC and doxycycline eye drop could improve the CNV complication. Also, NAC was an effective treatment against the inflammatory pathway involved in CEES-injured cornea.
NAC and doxycycline eye drop could improve the CNV complication. Also, NAC was an effective treatment against the inflammatory pathway involved in CEES-injured cornea.
Cross-culturally translate, adapt, and validate Roland Morris Disability Questionnaire (RMDQ) in Amharic language in Ethiopia.

The English version RMDQ was translated into Amharic and back-translated into English. An expert review committee reviewed the translations and created Amharic version of the RMDQ (RMDQ-Am). Pilot testing and cognitive debriefing of the RMDQ-Am were conducted with a sample of 20 individuals with LBP. The RMDQ-Am was administered to 240 individuals with LBP from three rehabilitation centers to determine its psychometric properties. Internal consistency of the tool was determined by Cronbach's alpha. Test-retest reliability was determined by the Intraclass correlation coefficient. The Standard Error of Measurement (SEM), Minimum Detectable Change (MDC), and the Bland Altman Limit of Agreement (LOA) was also determined. The Short-Form Health Survey (SF-36) Bodily Pain and Physical Functioning subscales were used to assess convergent validity. Exploratory Factor Analysis (EFA) was usehe Roland Morris Disability Questionnaire (RMDQ).The RMDQ was successfully translated, adapted, and validated into the Amharic language and the Ethiopian context (RMDQ-Am).The RMDQ-Am is a reliable outcome measure among the Ethiopian population with LBP, as demonstrated by the good internal consistency (α = 0.88) and excellent test-retest reliability (ICC = 0.91).There is a moderate negative correlation between the RMDQ-Am and the Physical Functioning (Rho = -0.62, p  less then  0.01) and Bodily Pain (Rho = -0.41, p  less then  0.01) subscales of the SF-36.The RMDQ-Am can be used in clinical and research settings to measure LBP-related disability and its impact among individuals living with LBP in Ethiopia.
Pain has psychological, social, physical and spiritual dimensions and therefore this experience is influenced by culture. The aim of this study was to explore the experiences and beliefs of Arab Muslim patients with low back pain (LBP) in Bahrain.

We recruited Arab Muslim patients attending physiotherapy with LBP ≥3 months, and ≥18 years of age. Socio-demographic information and a Visual Analogue Scale (VAS) score for pain intensity were collected. Focus groups were conducted between 2013-2014, using pre-determined semi-structured interview questions. Qualitative content analysis was applied with single counting and inclusion of negative instances.

18 participants attended three focus groups (14 females and 4 males) with a mean VAS(SD) = 5.28(±1.97). Five themes were identified; (1) loss of independence, (2)change in identity causes distress, (3) beliefs and attitudes towards low back pain, (4)trying to cope with LBP, and (5)experiences within the healthcare system.

Religious and cultural beliefs inflP; such as prioritising patient education and joint decision-making.Introduction The 6 F Tack Endovascular System® is approved by the United States Food and Drug Administration (FDA) for post-percutaneous transluminal angioplasty (PTA) dissection repair in the superficial femoral and proximal popliteal arteries, and the 4 F System for post-PTA dissection repair in the mid/distal popliteal, peroneal and tibial arteries. The latter is the first FDA approval for an infra-popliteal implantable device.Areas covered An evaluation of the Tack Endovascular System® design and a summary of the current safety and efficacy data.Expert opinion Endovascular intervention for the treatment of symptomatic peripheral arterial disease (PAD) in the lower extremities is complicated by long-lesion length, extensive calcification and, below the knee, narrow vessel diameter. PTA is a foundational element for the treatment of these lesions and works by causing a controlled dissection and vessel expansion of the target lesion. Occasionally, dissections can extend beyond the target lesion and/or become hemodynamically significant due to lumen impingement necessitating additional intervention. Historically these dissections were treated with the use of stents, prolonged balloon inflation time or went untreated. The Tack Endovascular System® was designed to provide operators a safe and effective device which could repair post-PTA dissections while preserving future treatment options.The evaluation of erythrocytosis can fail to detect hemoglobin (Hb) variants if a thorough and systemic investigation is not undertaken. Here we report the identification of a novel high-oxygen affinity Hb that was previously misclassified as polycythemia vera (PV). Given that treatment recommendations can vary significantly based on the etiology of erythrocytosis, familiarity with reference laboratories and their methodologies is of crucial importance to conducting a precise consultation, as in the case of our Hb variant, named Hb San Francisco-KP [β34(B16)Val→Ala, HBB c.104T>C] for the city and medical center where it was discovered. The Mayo Clinic's (Rochester, MN, USA) Erythrocytosis Evaluation (REVE) panel was instrumental in establishing a final diagnosis. Of note, the patient's clinical response to phlebotomy distinguishes this subtype from many of the other high affinity Hbs where the erythrocytosis is primarily compensatory and not in need of venesection.
Intrathyroidal parathyroid adenoma (IPA) is rare and may easily be mistaken for thyroid nodule in ultrasonography. The aim of this study was to investigate the characteristic features of IPA and explore the value of preoperative and intraoperative ultrasound in the diagnosis and localization of IPA.

13 of 216 patients who were found to have intrathyroidal parathyroid lesions underwent parathyroidectomy in our hospital because of PHPT. According to the relationship between parathyroid adenoma and thyroid gland, parathyroid adenoma was divided into extra-thyroid type or intra-thyroid type (partial or complete) and the results were compared with surgical and histopathological reports as gold standard. The sonographic features of intrathyroidal parathyroid lesions were analyzed retrospectively.

A total of 12 intrathyroidal lesions showed profoundly hypoechoic solid nodules with well-defined border, abundant blood flow and polar feeding vessels originating from the superior or inferior thyroid artery (92.3%,e and intraoperative ultrasound could be helpful in the localization and treatment of intrathyroidal parathyroid diseases.
An intrathoracic goiter (ITG) is defined as a thyroid extension below the sternal notch. Compared to cervical goiters, surgery for ITG is more challenging, with a higher risk of an extracervical approach. Ultrasound (US)-guided radiofrequency ablation (RFA) is a minimally invasive treatment modality. The purpose of this study was to prospectively evaluate the safety and efficacy of RFA in patients with ITG.

From a total of 324 patients who underwent thyroid RFA at a single medical center, 15 patients (mean age 52.2 years; 73.3% female) with 16 ITGs were included and classified into three grades and three types using the cross-section imaging CT system. Clinical features and demographics, degree of extension, RFA details, goiter volume, and complications were analyzed.

Mean pre- and post-RFA goiter volumes as measured by US were 106.62 ± 61.82 and 25.09 ± 14.22 mL respectively, with a volume reduction rate (VRR) of 75.5% (
 < 0.001) at 6 months. The VRR as measured by CT/MRI was 57.0 ± 10.0% (
 < 0.001) at 6 months. The intrathoracic length reduction rate at 6 months was 44.9 ± 39.2% (
 = 0.001). In addition, 4 (25%) ITGs had total regression of the intrathoracic extension, with a downgrade from grade 1 to cervical goiter. Mean pre- and post-RFA symptom and cosmetic scores were 1.53 and 0.15 (
 = 0.001), and 2.67 and 2.00 (
 = 0.001), respectively. One patient had transient vocal cord palsy and another had perithyroidal and mediastinal hemorrhage.

US-guided RFA is an effective treatment for ITG in terms of both cervical and intrathoracic reductions with an acceptable complication rate.
US-guided RFA is an effective treatment for ITG in terms of both cervical and intrathoracic reductions with an acceptable complication rate.
Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous T-cell malignancies representing 5%-10% of aggressive lymphomas. The prognosis is poor for patients with relapsed/refractory (R/R) disease, with a median overall survival of less than 6 months and no standardized treatments. We discuss the role of the phosphatidylinositol 3-kinase (PI3K) γδ inhibitor duvelisib as bridge to allotransplantation in a patient with R/R PTCL.

Case report.

A 55-year-old woman diagnosed with relapsed nodal PTCL with T-follicular helper phenotype received PI3K γδ inhibitor duvelisib in the context of the phase II PRIMO clinical trial. After two cycles at a dose of 75 mg twice daily, the patient achieved complete response (CR), which was subsequently consolidated with human leukocyte antigen fully matched unrelated donor allotransplantation. No major toxicities were recorded during the duvelisib treatment period or during hospitalization for allotransplantation. At the latest follow-up, the patient was alive and still in CR 10 months posttransplant.
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