The impact of left common pulmonary vein on cryoballoon ablation of atrial fibrillation. A meta-analysis

IntroductionConflicting results regarding the impact of left common pulmonary vein (LCPV) on clinical outcome of atrial fibrillation (AF) ablation with cryoballoon technology have been reported.MethodsWe systematically searched PubMed and Cochrane library for articles that compared the arrhythmia recurrence rate after cryoballoon ablation between patients with normal pattern PVs and patients with LCPV. Studies of first ablation for persistent and paroxysmal AF using the 28 mm Arctic Front Advance, Medtronic cryoballoon (CB-A) reporting clinical success rates at a mean follow-up of ≥12 months were included. Data were analyzed by applying a random effects model.ResultsA total of 5 studies with a total of 1178 patients met our predefined inclusion criteria. After a mean follow-up of 18.4 months, the overall success rate of CB-A ablation among patients with persistent and paroxysmal AF was 57%; in the LCPV group the success rate was 46% and in the normal anatomical pattern group it was 61%. No significant heterogeneity was noted among the studies (I² = 35.8%; Q (df = 3) = 6.23 p-value = 0.18). Arrhythmia recurrence after CB-A ablation was not statistically significant between the two groups (LogOR 0.24; 95% CI [-0.16-0.63]; p-value = 0.23). No significant difference in PNI was observed between the two groups (p-value = 0.693).ConclusionThe presence of LCPV does not affect the long-term outcome of paroxysmal and persistent atrial fibrillation ablation with 28 mm CB-A compared to normal left PVs pattern.     

“Fast” women? The effects of childhood environments on women's developmental timing,mating strategies,and reproductive outcomes

The fast-slow paradigm of life history theory has been a popular approach to individual differences in the evolutionary behavioral sciences. Currently, however, the fast-slow paradigm faces several theoretical and empirical challenges. Motivated by questions regarding the validity of certain assumptions of the paradigm, the current study provides an empirical investigation of human female “fast” versus “slow” strategies. In a sample of 1867 women recruited using MTurk, we use structural equation modeling (SEM) to test whether childhood exposure to different environmental variables had unique effects on proposed life history traits, whether mediated by—or independent of—pubertal timing. Models also test whether the proposed life history traits covary with one another as expected by the paradigm. Data reveal that exposure to violence and poor health in particular, but not environmental harshness or unpredictability in general, had significant effects on pubertal timing. Pubertal timing appeared to mediate effects of childhood environments on age at sexual debut, but not any other adult outcome (e.g., sociosexual orientations, reproductive outcomes). Some associations with mating strategies were incompatible with assumptions of the prevailing fast-slow paradigm; for instance, greater short-term mating orientation was positively associated with childhood socioeconomic status and negatively associated with offspring number. These results highlight the need for a new or revised theoretical approach to understanding developmental, mating, and reproductive strategies.     

Clinical,Hormonal, and Genetic Characteristics of 5α-Reductase Type 2 Deficiency in 103 Chinese Patients

Objective5α-Reductase type 2 (5α-RD2) deficiency causes variable degrees of undervirilization in patients. The correlation between its genotype and phenotype is unclear.MethodsWe retrospectively evaluated 103 patients with 46,XY disorders of sex development who were diagnosed with 5α-RD2 deficiency.ResultsThe prevalence of female sex assignment (P = .008) and the incidences of cryptorchidism (P = .0003) and bifid scrotum (P = .0002) in the non-p.R227Q variant group were higher, but there were no significant differences in the incidences of hypospadias and isolated microphallus. The external masculinization score in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P = .019) and compound heterozygous p.R227Q variant groups (P = .013). The level of anti-Mullerian hormone in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P < .001) and compound heterozygous p.R227Q variant groups (P = .006). The testosterone-to-dihydrotestosterone ratio of the homozygous p.R227Q variant group was higher than that of the non-p.R227Q variant (P = .018) and compound heterozygous p.R227Q variant groups (P = .029). Twenty-three reportedly pathogenic variants and 11 novel steroid 5α-reductase 2 (SRD5A2) variants were identified.ConclusionCompared with patients without p.R227Q, patients with p.R227Q exhibited higher external masculinization scores and anti-Mullerian hormone expression, a lower prevalence of female sex assignment, and lower incidences of cryptorchidism and bifid scrotum. We identified 23 reportedly pathogenic SRD5A2 variants and 11 novel SRD5A2 variants that led to 5α-RD2 deficiency. We established a genotype-phenotype correlation, and patients with p.R227Q showed a relatively mild phenotype.     

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study

BackgroundCardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn’t been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state.MethodsThis is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls).ResultssP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases.ConclusionOur study supports the previous researches’ results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.     

The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review

ObjectiveThe impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT.MethodsA systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included.ResultsFrom 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration.ConclusionsThe results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT.Systematic Review RegistrationPROSPERO, identifier CRD42022323757.     

Aging impact on amyloid precursor protein neuronal trafficking

Neurons live a lifetime. Neuronal aging may increase the risk of Alzheimer's disease. How does neuronal membrane trafficking maintain synapse function during aging? In the normal aged brain, intraneuronal beta-amyloid (Aβ) accumulates without Alzheimer's disease mutations or risk variants. However, do changes with neuronal aging potentiate Aβ accumulation? We reviewed the membrane trafficking of the amyloid precursor protein in neurons and highlighted its importance in Aβ production. Importantly, we reviewed the evidence supporting the impact of aging on neuronal membrane trafficking, APP processing, and consequently Aβ production. Dissecting the molecular regulators of APP trafficking during neuronal aging is required to identify strategies to delay synaptic decline and protect from Alzheimer's disease.     

Chemical evaluation of partially acidulated phosphate rocks and their impact on dry matter yield and phosphorus uptake of maize

Previous studies investigated the direct application of phosphate rock and its partially acidulated to enhance its solubility compared to soluble fertilizers. However, the interaction between the effect of particles diameter and partial acidulation of phosphate rock on phosphorus (P) availability and its effect on dry matter yield and P uptake is still elusive. This study was conducted to assess the effect of partially acidulated Egyptian phosphate rocks with different particle size diameters on P availability and its effect on dry matter yield and P uptake of maize (Zea mays L.). A pot experiment was conducted on maize plants grown on light clay soil for 42 days. Acidulation was done by mixing phosphate rock with single superphosphate or triple superphosphate at a total rate of 200 mg P kg^?1 with five acidulation mix ratios (100:0, 75:25, 50:50, 25:75, and 0:100). Different particle size diameters of phosphate rocks (500, 212, 75, and <45 µm included nano-particles ranged from 69.3 to 25.7 nm) were used. We found that dry matter yield and P uptake increased significantly due to the use of partially acidulated phosphate rocks especially when triple superphosphate was used for acidulation and the mixing ratio of 50:50 was the best. We also found that maize yield and P uptake increased significantly with decreasing particle size. It is recommended to use finely grounded partially acidulated phosphate rocks with particles diameter less than 45 µm at acidulation ratio 50% and no need to increase acidulation ratio above that as a slow-release phosphate fertilizer.     

Sympathetic tone dictates the impact of lipolysis on FABP4 secretion

Levels of circulating fatty acid binding protein 4 (FABP4) protein are strongly associated with obesity and metabolic disease in both mice and humans, and secretion is stimulated by β-adrenergic stimulation both in vivo and in vitro. Previously, lipolysis-induced FABP4 secretion was found to be significantly reduced upon pharmacological inhibition of adipose triglyceride lipase (ATGL) and was absent from adipose tissue explants from mice specifically lacking ATGL in their adipocytes (ATGL^AdpKO). Here, we find that upon activation of β-adrenergic receptors in vivo, ATGL^AdpKO mice unexpectedly exhibited significantly higher levels of circulating FABP4 as compared with ATGL^fl/fl controls, despite no corresponding induction of lipolysis. We generated an additional model with adipocyte-specific deletion of both FABP4 and ATGL (ATGL/FABP4^AdpKO) to evaluate the cellular source of this circulating FABP4. In these animals, there was no evidence of lipolysis-induced FABP4 secretion, indicating that the source of elevated FABP4 levels in ATGL^AdpKO mice was indeed from the adipocytes. ATGL^AdpKO mice exhibited significantly elevated corticosterone levels, which positively correlated with plasma FABP4 levels. Pharmacological inhibition of sympathetic signaling during lipolysis using hexamethonium or housing mice at thermoneutrality to chronically reduce sympathetic tone significantly reduced FABP4 secretion in ATGL^AdpKO mice compared with controls. Therefore, activity of a key enzymatic step of lipolysis mediated by ATGL, per se, is not required for in vivo stimulation of FABP4 secretion from adipocytes, which can be induced through sympathetic signaling.     

The role of amino acid metabolism alterations in pancreatic cancer: From mechanism to application

The incidence of pancreatic cancer is increasing in both developed and developing Nations. In recent years, various research evidence suggested that reprogrammed metabolism may play a key role in pancreatic cancer tumorigenesis and development. Therefore, it has great potential as a diagnostic, prognostic and therapeutic target. Amino acid metabolism is deregulated in pancreatic cancer, and changes in amino acid metabolism can affect cancer cell status, systemic metabolism in malignant tumor patients and mistakenly involved in different biological processes including stemness, proliferation and growth, invasion and migration, redox state maintenance, autophagy, apoptosis and even tumor microenvironment interaction. Generally, the above effects are achieved through two pathways, energy metabolism and signal transduction. This review aims to highlight the current research progress on the abnormal alterations of amino acids metabolism in pancreatic cancer, how they affect tumorigenesis and development of pancreatic cancer and the application prospects of them as diagnostic, prognostic and therapeutic targets.     

The Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study

ObjectiveThe optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT.MethodsA single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated.ResultsClinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (β = –0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05).ConclusionLow-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.     

Assessing aging impact on growth potential of Vitamin E primed soybean seeds via biochemical profiling

Soybean [Glycine max (L.) Merr.] is a high value crop owing to its nutrient rich profile, consisting of some of the largest reserve of proteins and oils among all plant crops. High yielding soybean variety seeds are of great intrinsic value as part of strategies to gain larger yield outputs over the years. These seeds often tend to lose their viability and corresponding storage period. The study is primarily focused on understanding and estimating the impact of storage conditions and influence of biochemical changes that leads to deteriorating seed health. Vitamin E is an essential compound that provides shielding effect to plant seeds against environmental stress. For this purpose seed priming of vitamin E was performed with a concentration of 300mgL^-1 applied on to seeds. A total of seven promising cultivars were accessed for this; including Swat-20, Swat-84, NARC-2. Malakand, Rawal, Ajmeri and FaisalSoy. Results shows that all cultivars tend to lose their yield potential which is greatly in line with storage induced biochemical changes. Among the cultivars, Swat-84 and Swat-20 were resilient to an extent towards harmful storage stress impact. The present study has shown that application of vitamin E seed coating tend to enhance positive traits in stored seeds (including concentrations of CAT, SOD, TSS, etc.) in comparison to untreated seeds showing a healthy impact of the treatment on seed health under storage conditions. It is suggested that storing vitamin E treated seeds under optimum conditions as an effective method for attaining viable seeds after long terms storage. Findings of the present study can be used for future studies, assessment and designing of seed storage system in a manner to reduce negative impact on seed growth potential during long term storages.     

The hidden potential of glycomarkers: Glycosylation studies in the service of cancer diagnosis and treatment

Changes in the glycosylation process appear early in carcinogenesis and evolve with the growth and spread of cancer. The correlation of the characteristic glycosylation signature with the tumor stage and the appropriate therapy choice is an important issue in translational medicine. Oncologists also pay attention to extracellular vesicles as reservoirs of new cancer glycomarkers that can be potent for cancer diagnosis/prognosis. In this review, we recall glycomarkers used in oncology and show their new glycoforms of improved clinical relevance. We summarize current knowledge on the biological functions of glycoepitopes in cancer-derived extracellular vesicles and their potential use in clinical practice. Is glycomics a future of cancer diagnosis? It may be, but in combination with other omics analyses than alone.     

Impact on S. aureus and E. coli Membranes of Treatment with Chlorhexidine and Alcohol Solutions: Insights from Molecular Simulations and Nuclear Magnetic Resonance

Membranes form the first line of defence of bacteria against potentially harmful molecules in the surrounding environment. Understanding the protective properties of these membranes represents an important step towards development of targeted anti-bacterial agents such as sanitizers. Use of propanol, isopropanol and chlorhexidine can significantly decrease the threat imposed by bacteria in the face of growing anti-bacterial resistance via mechanisms that include membrane disruption. Here we have employed molecular dynamics simulations and nuclear magnetic resonance to explore the impact of chlorhexidine and alcohol on the S. aureus cell membrane, as well as the E. coli inner and outer membranes. We identify how sanitizer components partition into these bacterial membranes, and show that chlorhexidine is instrumental in this process.     

Histological changes of cervical tumours following Zanthoxylum acanthopodium DC treatment,and its impact on cytokine expression

Cervical cancer is the second most lethal cancer in Indonesia, behind breast cancer. One of the reasons cancer cells are difficult to treat is that the immune system is sometimes unable to recognise them as foreign. Cytokinin therapy is carried out so that the immune system can strengthen its response to cancer cells, with the aim of slowing or stopping the development of malignant cells. Zanthoxylum acanthopodium DC, also known as andaliman, is an Indonesian herb and a member of the Rutaceae family. It is rich in antioxidants and has anti-inflammatory and anti-cancer properties. The current study aimed to investigate the histological changes and changes in the expression of cytokines, such as IL-10, IL1β, VEGFR1, and TGFβ1, associated with andaliman treatment. Sample tissues and serums extracted from cervical cancer rat models were used. Rats were divided into five groups: a control group (C?), cancer model group (C+), cancer with a dose of Z. acanthopodium methanolic extract (ZAM) 100 mg/body weight (BW) ZAM (ZAM100), cancer with a dose of ZAM 200 mg/BW ZAM (ZAM200), and cancer with a dose of ZAM 400 mg/BW ZAM (ZAM400). Treatment lasted for 1 month. Blood samples were prepared for ELISA analysis, and cervical tissue was stained for immunohistochemistry using antibodies against IL-10, IL-1β, VEGFR1, and TGFβ1. Administration of ZAM had no significant effect on rat body weight and cervical organs (p > 0.05). However, it impacted haematological parameters in rats with cervical cancer (p < 0.05). Elevated malondialdehyde levels may be linked to superoxide dismutase deficiency in tumour tissue. ZAM significantly decreased the expression of IL1β, TGFβ1, and VEGFR1 (p < 0.01), while it increased the expression of IL-10. Therefore, ZAM may be a potential target for molecular cytokine therapy for cervical cancer.     

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions

ObjectiveThe objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes.MethodsA literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review.ResultsMinimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer.ConclusionSurgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.     

Dosimetric impact on changes in target volumes during intensity-modulated radiotherapy for nasopharyngeal carcinoma

Background and purposeTo assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact.Patients and methodsTwenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated.ResultsWe observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01).ConclusionTumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients.     

The Prevalence of Metabolic and Endocrine Disturbances on Fracture Nonunion

ObjectiveThis study aims to determine the prevalence of metabolic disturbance in all fracture nonunion cases and identify the most common endocrine abnormalities seen using a simple screening algorithm.MethodsA retrospective review study was performed evaluating patients who underwent operative intervention for nonunion from January 2010 to December 2018 at 2 level-1 trauma centers. Preoperative laboratory values were recorded for a 9-test “nonunion panel.” A metabolic or endocrine abnormality, specifically an abnormality in the thyroid or parathyroid axis, was evaluated.Results42% of patients had an undiagnosed metabolic laboratory abnormality. When multiple tests were used, the rate of metabolic dysfunction was between 60% and 75%, depending on the definition of vitamin D insufficiency vs deficiency used.ConclusionResults indicate a relatively high prevalence of metabolic disturbance in patients with nonunion and suggest metabolic screening for all nonunion patients not only those without a mechanical or infectious cause.Level of EvidenceIV, retrospective case series.     

Arterial Stiffness and Cardiometabolic-Based Chronic Disease: The Kardiovize Study

ObjectiveArterial stiffness (ArSt) describes a loss of arterial wall elasticity and is an independent predictor of cardiovascular events. A cardiometabolic-based chronic disease model integrates concepts of adiposity-based chronic disease (ABCD), dysglycemia-based chronic disease (DBCD), and cardiovascular disease. We assessed if ABCD and DBCD models detect more people with high ArSt compared with traditional adiposity and dysglycemia classifiers using the cardio-ankle vascular index (CAVI).MethodsWe evaluated 2070 subjects aged 25 to 64 years from a random population-based sample. Those with type 1 diabetes were excluded. ABCD and DBCD were defined, and ArSt risk was stratified based on the American Association of Clinical Endocrinologists criteria.ResultsThe highest prevalence of a high CAVI was in stage 2 ABCD (18.5%) and stage 4 DBCD (31.8%), and the lowest prevalence was in stage 0 ABCD (2.2%). In univariate analysis, stage 2 ABCD and all DBCD stages increased the risk of having a high CAVI compared with traditional classifiers. After adjusting for age and gender, only an inverse association between obesity (body mass index ≥30 kg/m²) and CAVI remained significant. Nevertheless, body mass index was responsible for only 0.3% of CAVI variability.ConclusionThe ABCD and DBCD models showed better performance than traditional classifiers to detect subjects with ArSt; however, the variables were not independently associated with age and gender, which might be explained by the complexity and multifactoriality of the relationship of CAVI with the ABCD and DBCD models, mediated by insulin resistance.