The Taklimakan Desert is the largest desert in China and the second-largest mobile desert in the world. It is characterized by an increasing altitude gradient from north to south. In this study, a total of 48 sand samples were collected in the Taklimakan Desert, and variations in physicochemical parameters and bacterial communities in the samples and the correlation between them were explored. The bacterial community was characterized using 16S rRNA gene sequencing. The obtained taxonomic data revealed significant differences in the relative abundance of bacterial communities and populations among the samples. The predominant phyla were Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes. The abundance of Actinobacteria increased gradually while that of Firmicutes decreased gradually with the increase in altitude. At the genus level, the abundance of Bacillus showed a gradual decrease while that of unclassified Micrococcaceae showed a gradual increase. Altitude and pH were the primary factors that shaped the bacterial communities in the desert. Besides, Ca2+ and P were also significantly correlated with the abundance of bacterial communities. The indicator taxa were significant differences in the surface and the subsurface samples.

A document by Yuqi Liu. Click on the document to view its contents.

Objective To investigate the risk of congenital heart defects (CHD) and other congenital anomalies (CA) associated with first trimester use of macrolides. Design Population-based case-malformed control study. Setting Thirteen European countries. Population Data on 145,936 livebirths, stillbirths and terminations of pregnancy for CA from 15 EUROCAT registries, covering 9 million births 1995–2012. Methods Cases were babies with CHD, anencephaly, orofacial clefts, genital and limb reduction anomalies associated with antibiotic exposure in the literature. Controls were babies with other CA or genetic conditions. A meta-analysis of the literature, including this study, was conducted for CHD. Main outcome Odds ratios adjusted (AOR) for maternal age and registry, with 95% Confidence Intervals (95%CI). Results Macrolide exposure was recorded for 307 cases, 72 non-genetic controls, 57 genetic controls. AOR for CHD was not significantly raised (AOR 0.94, 95%CI: 0.70 – 1.26 vs non-genetic controls; AOR 1.01, 95%CI: 0.73 – 1.41 vs genetic controls), nor significantly raised for any specific macrolide. The risk of atrioventricular septal defect was significantly raised with exposure to any macrolide (AOR 2.98; 95%CI: 1.48 – 6.01), erythromycin (AOR 3.68, 95%CI: 1.28 – 10.61), and azithromycin (AOR 4.50, 95%CI: 1.30 – 15.58). Erythromycin, clarithromycin, azithromycin and clindamycin, were also associated with an increased risk of at least one other CA. Meta-analysis gave an overall CHD OR 1.14, 95%CI 0.90 –1.49 for macrolides. Conclusions Guidelines for macrolide use in pregnancy should consider the increased risk of specific CA. This is relevant for the potential use of azithromycin in the treatment of COVID-19.

AIM: This study aimed to assess the pharmacokinetics, tolerability, safety and exploratory analgesic efficacy of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine in advanced cancer patients with unrelieved pain. METHODS: The study was a non-blinded single arm, single escalating dose (n=5) [2.5 mg Δ9-THC and 2.5 mg CBD) and multiple escalating doses (up to 5.5 doses)] of a two-stage pilot study in patients diagnosed with advanced cancers and intractable pain (n=25). RESULTS: As the cannabis-based medicine dose increased, maximum plasma concentrations of all analytes were approximately proportional to dose. The bioavailability of 9-THC and CBD in this water-soluble nanoparticle formulation was approximately twice the bioavailability reported for a 9-THC/CBD formulation with ethanol. The water-soluble formulation in the current study resulted in a higher median (min, max) bioavailability of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49. 4.1), respectively). Analyte accumulation was not observed. In a subgroup of patients diagnosed with breast and prostate cancer with bone metastases, mean pain scores improvement from baseline was 40% (unadjusted) and 33% adjusted for rescue medication use. For all patients the most commonly reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively and nausea and vomiting that affected 18 (72%) patients. CONCLUSIONS: The water-soluble cannabis-based medicine (NanaBisTM) provided acceptable bioavailability for Δ9-THC and CBD, appeared safe and tolerable in cancer with uncontrolled pain with preliminary evidence of analgesic efficacy.

Optimal treatment for Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph+ MPAL), particularly in elderly patients with comorbidities, has not been established. We present the elderly Ph+ MPAL case who discontinued initial treatment with dasatinib and whose disease was successfully controlled by low-dose imatinib with monitoring of drug concentrations in blood.

Multiple breakup refers to a sequence of events through which a single droplet eventually produces multiple daughter droplets at a given flow condition. It is a more common phenomenon than binary breakup assumed in the existing breakage kernel models. Using phase-field lattice Boltzmann method, this work investigates the effects of Reynolds number, capillary number and soluble surfactant on multiple breakup in shear flow. We find that the critical capillary number in multiple breakup decreases as Reynolds number increases, and the regime map for a surfactant-free system could be classified into the non-breakup, elementary breakup, multiple breakup, filament and coalescence regimes. In the system of surfactants, the multiple breakup regime widens and the coalescence regime narrows. A correlation is then proposed to predict the number of breakup events and daughter droplets at a confinement ratio of 0.5. This may provide some clues on developing new breakage kernels in population balance modeling.

Debate: The placenta is the villain or victim in the pathogenesis of preeclampsia.

Abstract Concomitant use of Vitamin K antagonists (VKA) and statins is frequent in cardiovascular patients. However, clinical guidelines on this drug combination are divergent. Therefore, we performed a systematic review according to the PRISMA guidelines to evaluate the effect of statin initiation on coagulation among VKA users. Applying two broad search strategies for the drug interaction between VKA and statins in both Embase and Pubmed, 8,623 unique hits were obtained. In the final sample eight studies were included. The most frequent used VKA in the studies was warfarin while simvastatin was the most commonly initiated statin. All included studies showed a minor increase in the anticoagulant effect of VKA following statin initiation during VKA treatment. The reported increases in mean INR ranged from 0.15-0.65. The effect is likely to be of limited clinical relevance but should be evaluated individually.

High-quality ZSM-5 zeolite membranes were successfully synthesized on the outer surface of tubular α-alumina substrates by manipulating the microstructure of the zeolite layer using a new different-sized seeding (DSSM) in combination with variable-temperature/time (VTT) methodd. In this method the microcracks/defects in the primary seed layer are filled by smaller seeds and effectively eliminated using a proper temperature/time profile, resulting in a significant increase in selectivity without scarifying permeance. The effects of number and combination of seed layers, seed size, and synthesis conditions on the microstructure, N2/SF6 gas permeation, and H2/CO2 separation performance of membranes are evaluated in detail. The synthesized ZSM-5 membranes show the microstructure of thin, fully inter-grown, and densified zeolite layer that is responsible for high selectivity without any negative effect on the permeance. The best synthesized defect-free membranes exhibited a very low H2/CO2 selectivity of 0.1 with CO2 permeance of 3×10-5 mol m-2 s-1 Pa-1.

Acute pericarditis and pericardial effusion are rare extrapulmonary presentations of COVID-19. They can occur without concomitant pulmonary disease or myocardial injury. A high index of suspicion is necessary to assure early diagnosis and treatment.

Spontaneous and isolated bilateral external iliac artery dissection is extremely rare. We present a case of isolated bilateral external iliac artery dissection secondary to emotional stress. We believe this to be the first case with this condition secondary to emotional stress in patient without connective tissue disorder.

Serum sickness, a reaction characterized by fever, rash, myalgia, and arthralgia, can occur in patients who receive chimeric monoclonal antibody therapy. Serum sickness is considered as a rare adverse event following rituximab therapy. We report a case of serum sickness in a newly treated patient with rituximab for pemphigus vulgaris.

Here, we describe a successful catheter-based closure of a recurrent post-infarction VSR using a new custom-made device in a 50-year-old man who had previously undergone emergency surgical repair for acute PIVSR with bovine pericardial patch, coronary artery bypass grafting and mitral valve replacement with mechanical prosthesis.

Rationale, aims and objectives: The efficacy and safety of drugs can be improved by rational prescription and personalization of medicine for each patient. Pharmacogenomics information (PGx) in drug labels (DL) is important for the personalization of medications because genetic differences may affect both drug efficacy and safety. Providing adequate PGx to patients has ethical implications. The aim of this study was to determine if there are discrepancies among various agency-approved labels for the same active ingredient and where the labels approved by the Turkish Medicines and Medical Devices Agency (TMMDA) stand regarding the inclusion of PGx and discuss these ethical implications. Methods: DL annotations from the Pharmacogenomics Knowledgebase and DLs approved by the TMMDA were analyzed according to information and action levels, which are “testing required”, “testing recommended”, “actionable”, and “informative”. Results: There are 381 drugs listed in PharmGKB drug label annotations and 278 of these have biomarkers. A total of 242 (63.52%) drugs are approved and available in Turkey. Of these, 207 (54.33%) contain the same information as in or similar to that in the labels approved by the other agencies. The presence and level of information varied among the DLs approved by different agencies. The inconsistencies may have a significant effect on the efficacy and the safety of drugs. Conclusion: These findings suggest an urgent need for the standardization of pharmacogenomics information globally because it may not only affect the efficacy and safety of medications but also essential ethical rules regarding patient rights.

Introduction: Knowledge of factors causing pacing-induced cardiomyopathy (PICM) is incomplete. We sought to estimate the incidence and predisposing factors for PICM in South Asian population and evaluate if the risk they portend adds up. Methods: Consecutive patients with preserved LVEF undergoing pacemaker (PM) implantation between 2012 and 2018 were analysed. Results: A total of 749 patients (68.4% male; mean age 59.2 ± 14.08 years) were included in the analysis. PICM developed in 74 (9.9 %) patients over a median follow up of 2.2 years (IQR 1.1-3.2). Pre-implant LVEF, paced QRS duration and RV pacing burden were independent predictors of PICM. Using 90% specificity cut-off values for LVEF and paced QRS, and the value separating lowest tertile of RV pacing from the higher tertiles, three risk factors were identified: (i) baseline LVEF < 55%, (ii) paced QRS duration > 160 msec, and (iii) RV pacing burden > 33%. Patients with two or more risk factors were at the highest risk (OR 11.62, 95% CI 4.62 - 29.21, p-value < 0.001) for developing PICM while those with one risk factor had an intermediate risk (OR 3.89, 95% CI 1.62 - 9.34, p-value 0.002) when compared to those without any risk factors. Conclusion: Low-normal baseline LVEF, wider paced QRS and higher RV pacing burden independently predicted the development of PICM. The presence of ≥2 factors increased the odds of PICM, twelve-fold. Striving to get a narrower paced QRS, the only modifiable of the three risk factors, will help mitigate the development of PICM.

Introduction: Recent research has shown that Brugada syndrome (BrS) is associated with interstitial fibrosis in the right ventricular outflow tract (RVOT) epicardium, thus suggesting that BrS does not just involve cardiac channelopathy but also includes cardiomyopathy. On the other hand, Brugada pattern ECGs are often observed in patients with pectus excavatum. The purpose of this study was to investigate whether thoracic deformity, along with mechanical compression of RVOT, were associated with BrS. Methods and Results: We recruited 17 male patients with symptomatic BrS, 32 male patients with asymptomatic BrS, and 30 age-matched male controls. Using computed tomography (CT) scans, we measured the maximal internal transverse diameter of the thorax (T) and the shortest anteroposterior depth from the internal aspect of the sternum to the anterior cortex of the vertebral body (D) at the level of the RVOT. We then evaluated the fragmented QRS (f-QRS) in the right precordial leads. D was significantly shorter, while T divided by D (T/D) was significantly greater, in patients with symptomatic and asymptomatic BrS than in the controls. Six patients with pectus excavatum (T/D≥3.25) were included in the BrS population. The f-QRSs was more frequently observed in symptomatic and asymptomatic BrS patients than in controls. The positive spikes within the QRS complex were more prevalent in patients with a greater T/D. Conclusion: Our results suggested that a narrow anteroposterior thoracic space could be associated with BrS via mechanical compression of the RVOT.

Background: There exist sex differences in the clinical profile, management, and outcome of atrial fibrillation (AF). Catheter ablation of AF has become a first-line therapy and has markedly made headway over recent decades. Little is known about sex differences and temporal trends in hospitalization for catheter ablation of AF in the real-world setting. Conclusions: Safety of catheter ablation for AF were comparable in both sexes. In contrast, the women showed a higher CHA2DS2-VA score compared with the men. The percentage of patients with CHA2DS2-VA score ≥2 increased more quickly in women than men. Further sex-specific research is warranted to reduce this sex disparity.

Numerical optimization of the manufacturing process of hybrid lightweight struc- tures consisting of fiber-reinforced plastics (FRP) is of high importance. It can reduce the time to market and can also avoid the production of costly prototypes. To model the considered thermoforming process, the temperature dependent defor- mation mechanisms have to be characterized and modeled within a finite element framework. An industry-oriented approach based on the parameterization of a mate- rial model implemented in LS-DYNA is introduced. The accordingly parameterized material model for the FRP is eventually applied in the simulation of thermoforming processes to show the influence of process and material parameters on the forming behavior of the thermoplastic prepreg.

Plants respond differently to neighbor identity showing plasticity in traits. However, solid experiment evidence on the functional traits of dioecious trees shaped by the recognition of neighbors with different gender and kinship is scarce. Here we examined the sexual and kinship interactions in a dioecious tree species, Diospyros morrisiana, by monoculturing and pair-culturing seedlings in a transparent gel system. Our results showed that sex-specific competition and kin recognition interacted and co-shaped the functional traits of D. morrisiana seedlings, especially root traits, while intra-sexual and non-kin neighbors facilitated the growth of seedlings. This implies kin- and gender-interactions depend on different mechanisms, kin selection and niche partitioning respectively, which is critical to understand how species coexist and traits are shaped in the nature.

Objectives: The aim of this analysis was to evaluate the predictors associated with increased risk of permanent pacemaker implantation (PPMI) following Transcatheter Aortic Valve Replacement (TAVR). Background: While TAVR has evolved as the standard of care for patients with severe aortic stenosis, conduction abnormalities leading to the need for PPMI is one of the most common post-procedural complications. Methods: A systematic literature search was performed to identify relevant trials from inception to May 2020. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. Results: 37 observational studies with 71,455 patients were identified. The incidence of PPMI following TAVR was 22%. Risk was greater in men and increased with age. Patients with diabetes mellitus, presence of right bundle branch block, baseline atrioventricular conduction block, and left anterior fascicular block were noted to be at higher risk. Other significant predictors include the presence of high calcium volume in the area below the left coronary cusp and non-coronary cusp, use of self-expandable valve over balloon-expandable valve, depth of implant, valve size/annulus size, pre-dilatation balloon valvuloplasty and post-implant balloon dilation. Conclusion: Fourteen factors were found to be associated with increased risk of PPMI after TAVR, suggesting early identification of high-risk populations and targeting modifiable risk factors may aid in reducing the need for this post TAVR PPMI.

A document by Erwinsyah Satria. Click on the document to view its contents.

Follicular helper T cells (Tfh) cells are generally considered critical in secondary lymphoid tissues; however, they are also identified in the circulation and in tertiary lymphoid structures in chronic inflammation. Gingival tissues with periodontitis reflect chronic inflammation so genomic footprints of Tfh cells should occur in these tissues and may differ related to aging effects. Methods: Macaca mulatta monkeys were used in a model of ligature-induced periodontitis [adult group (12-23 years of age); young group (3-7 years)]. Gingival tissue and subgingival microbiome samples were obtained at matched healthy sites, sites during ligature-induced disease, and in samples after clinical resolution. Microarray analysis examined Tfh genes (n=40) and the microbiome samples were examined using 16S MiSeq. Results: An apparent increase in the major transcription factor of Tfh cells, BCL6, was found with disease in both adult and young animals, while the master transcription markers of other T cell subsets were either decreased or showed minimal change. A number of the Tfh related genes, including surface receptors, secreted products and transcription factors were also significantly increased during disease. Unique microbial complexes showed patterns of interactions with Tfh genes that differed in health and disease. Conclusions: An increase in Tfh cell responsiveness occurred later in the progression of periodontitis, affected by age and strongly related to specific microbial complexes. The capacity of gingival Tfh cells to contribute to localized B cell activation and active antibody responses, including affinity maturation may be critical for controlling periodontal lesions and contributing to limiting and/or resolving the lesions.

This study aimed to understand the influence of naïve T cells in cytokine-induced killer (CIK) cell immunotherapy. A total of 68 patients with advanced solid tumors received activated autologous CIK cells weekly. Objective responses (complete or partial responses, CR/PR) were observed in 11 patients (16.2%, 11/68), with five of 11 responses lasting more than 8 months, and in 16 patients with SD (23.5%, 16/68). The absolute number of CD4+ naïve T cells in patients who achieved CR/PR was higher in SD and PD patients (CR/PR vs SD vs PD= 90 vs 149 vs 226 cells/μL), as were the absolute number of CD8+ naïve T cells (CR/PR vs SD vs PD= 47 vs 60 vs 103 cells/μL). Patients with high absolute numbers of naïve T cells ({greater than or equal to}298 cells/μL in naïve CD4+ and {greater than or equal to}156 cells/μL in naïve CD8+ cells) had a better response to ACT (PFS=8 months vs 5 months). In this study, we found that Patients with a high absolute number of naïve T cells in circulating blood had a better response to ACT, which showed the potential of naïve T cells as a biomarker for the response to ACT.

Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. Dendritic cells (DCs) are one of the most potent antigen-presenting cells (APC) and play pivotal roles in the enhancement or regulation of antiviral immune reactions. Aim of the present study was to investigate whether an HBV-infected maternal environment might influence the infants’ DC phenotype and function. Monocyte-derived DC (MoDC) of neonates born to HBsAg-positive mothers were studied phenotypically by Flow Cytometry (FCM) and functionally by mixed lymphocyte reaction (MLR) and enzyme-linked immunosorbent assay (ELISA). An electron microscope was used to analyze the morphological changes of MoDC. MoDC from neonates whose maternal HBV DNA was>5×107 copies/ml showed a reduced surface expression of CD80, CD86, and HLA-DR as compared to that in neonates whose maternal HBV DNA was negative (CD80: t=3.238, P=0.002; CD86: t=3.543, P=0.001; HLA-DR: t=2.785, P=0.008). T-cell proliferation assays also showed an impaired allostimulatory capacity in comparison to that in neonates whose maternal HBV DNA was negative, especially in the cultures at a DC: T cell ratios of 1:5 and 1:10 (t=-5.442, P<0.001; t=-2.195, P=0.042). Therefore, it can be speculated that the presence of high level of HBVDNA in the maternal environment might lead to minor phenotypic and functional alterations of MoDC from neonates and subsequent deficits in T-lymphocyte activation may contribute to viral persistence.