Super-Resolution STED Microscopy-Based Mobility Studies of the Viral Env Protein at HIV-1 Assembly Sites of Fully Infected T-Cells

The ongoing threat of human immunodeficiency virus (HIV-1) requires continued, detailed investigations of its replication cycle, especially when combined with the most physiologically relevant, fully infectious model systems. Here, we demonstrate the application of the combination of stimulated emission depletion (STED) super-resolution microscopy with beam-scanning fluorescence correlation spectroscopy (sSTED-FCS) as a powerful tool for the interrogation of the molecular dynamics of HIV-1 virus assembly on the cell plasma membrane in the context of a fully infectious virus. In this process, HIV-1 envelope glycoprotein (Env) becomes incorporated into the assembling virus by interacting with the nascent Gag structural protein lattice. Molecular dynamics measurements at these distinct cell surface sites require a guiding strategy, for which we have used a two-colour implementation of sSTED-FCS to simultaneously target individual HIV-1 assembly sites via the aggregated Gag signal. We then compare the molecular mobility of Env proteins at the inside and outside of the virus assembly area. Env mobility was shown to be highly reduced at the assembly sites, highlighting the distinct trapping of Env as well as the usefulness of our methodological approach to study the molecular mobility of specifically targeted sites at the plasma membrane, even under high-biosafety conditions.     

A Review of Impact of Textile Research on Protective Face Masks

COVID-19, classified as SARS-CoV-2, is causing an ongoing global pandemic. The pandemic has resulted in the loss of lives and has caused economic hardships. Most of the devices used to protect against the transmission of the novel COVID-19 disease are related to textile structures. Hence, the challenge for textile professionals is to design and develop suitable textile structures with multiple functionalities for capturing viruses, passivating them, and, at the same time, having no adverse effects on humans during the complete period of use. In addition to manufacturing efficient, biocompatible, and cost-effective protective face masks, it is also necessary to inform the public about the benefits and risks of protective face mask materials. The purpose of this article is to address the concerns of efficiency and efficacy of face masks by primarily reviewing the literature of research conducted at the Technical University of Liberec. The main focus is on the presentation of problems related to the specification of aims of face mask applications, mechanisms of capture, durability, and modes of sterilization. The recommendations, instead of conclusions, are addressed to the whole textile society because they should be leading players in the design, creation, and proper treatment of face masks due to their familiarity with the complex behavior of textile structures and targeted changes of structural hierarchy starting from polymeric chains (nano-level) and ending in planar textile structures (millimeter level) due to action by mechanical, physical and chemical fields. This becomes extremely critical to saving hundreds of thousands of lives from COVID-19.     

Mechanical Properties of Polypropylene: Additive Manufacturing by Multi Jet Fusion Technology

Multi jet fusion (MJF) technology has proven its significance in recent years as this technology has continually increased its market share. Recently, polypropylene (PP) was introduced by Hewlett-Packard for the given technology. To our knowledge, little is known about the mechanical properties of polypropylene processed by MJF technology. During this study, standardised specimens were printed under all of the major orientations of the machine’s build space. Each of these orientations were represented by five samples. The specimens then underwent tensile, bending and Charpy impact tests to analyse their mechanical properties. The structural analysis was conducted to determine whether PP powder may be reused within the MJF process. The mechanical tests showed that the orientation of the samples significantly influences their mechanical response and must be carefully chosen to obtain the optimal mechanical properties of PP samples. We further showed that PP powder may be reused as the MJF process does not significantly alter its thermal and structural properties.     

The optimal management of patient with permanent atrial fibrillation and heart failure with reduced ejection fraction – The permanent His-bundle pacing is a solution. A case report

Atrial fibrillation (AF) coexists frequently with heart failure (HF). Permanent His-bundle pacing (pHBP) seems to be an optimal approach to the management of patients with HF and concomitant AF, which are the indication for single chamber ICD implantation. This management allows to up-titrate the beta-blocker dose in order to prevent tachyarrhythmia with no risk of bradyarrhythmia or triggering deleterious right ventricular pacing. We present a case of 69-years-old male with AF, worsening HF and high burden of RV pacing. The upgrade from single chamber ICD to dual chamber ICD with pHBP alleviated the symptoms and contributed to substantial echocardiographic improvement.     

Spatial navigation impairment is proportional to right hippocampal volume

Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = -0.62, P < 0.001) and virtual (β = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.     

Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain

AIM: To characterize the antinociceptive action of the novel melatonin receptor(MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain. METHODS: Visceral pain was induced by intracolonic(ic) application of mustard oil or capsaicin solution or by intraperitoneal(ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or orally and their effects on pain-induced behavioral responses were evaluated. To identify the receptors involved, thenon-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor antagonist 4-P-PDOT, or the μ-opioid receptor antagonist naloxone were injected ip or intracerebroventricularly(icv) prior to the induction of pain. RESULTS: Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses in a dose-dependent manner. Neu-P12 was more effective and displayed longer duration of action compared to melatonin. The antinociceptive effects of Neu-P11 or Neu-P12 were antagonized by ip or icv. administered naloxone. Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT blocked the antinociceptive actions of Neu-P11 or Neu-P12. CONCLUSION: Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising.     

The aromatase inhibitor anastrozole is ineffective in the treatment of precocious puberty in girls with McCune-Albright syndrome

CONTEXT: Precocious puberty (PP) in girls with McCune-Albright syndrome (MAS) is characterized by episodic development of large unilateral ovarian cysts followed by sudden onset of vaginal bleeding. Some patients experience frequent bleeding as well as accelerated linear growth and advanced skeletal maturation. The use of anastrozole for the treatment of PP in this condition has not been well studied. OBJECTIVE: The objective of the study was to determine the safety and efficacy of the aromatase inhibitor anastrozole for the treatment of PP in girls with MAS. DESIGN AND SETTINGS: This was a prospective international multicenter study in which subjects received anastrozole 1 mg daily for 1 yr. PATIENTS: Twenty-eight girls 10 years of age or younger with MAS and progressive PP were enrolled. MAIN OUTCOME MEASURES: Vaginal bleeding, rate of skeletal maturation (change in bone age over change in chronological age), growth velocity, and uterine/ovarian volumes were measured. These indices were compared with a 6-month pretreatment interval. RESULTS: No difference in vaginal bleeding (mean number of days per year) was noted. Mean change in DeltaBA/DeltaCA, which was 1.25 +/- 0.77 at baseline, was -0.25 +/- 1.02 at study end (P = 0.22). Average growth velocity z score was 1.40 +/- 3.15 at study entry and 0.26 +/- 2.71 at 12 months (P = 0.10). Mean ovarian/uterine volumes were unaffected by anastrozole, and no significant adverse events occurred. CONCLUSIONS: Although it appears safe, anastrozole for 1 yr was ineffective in halting vaginal bleeding, attenuating rates of skeletal maturation, and linear growth in girls with MAS. Pharmacological strategies other than anastrozole should be pursued for the treatment of PP in this population.     

Does low-dose and short-term glucocorticoids treatment increase the risk of osteoporosis in rheumatoid arthritis female patients?

Rheumatoid arthritis (RA) is frequently complicated by peri-articular and generalized osteoporosis due to increased bone resorption by activated osteoclasts. Pro-inflammatory cytokines, such as TNF-alpha, interleukin 1 (IL1), and interleukin 6 (IL6) are thought, among other factors, to be directly responsible for this extra-articular complication of RA. Glucocorticoids (GCS) commonly prescribed in RA due to their strong anti-inflammatory effect are also well known for causing secondary osteoporosis during a prolonged use. An influence of low-dose GCS therapy (8.7 mg per day) on a bone turnover in female RA patients with or without previous history of GCS treatment was investigated by measuring bone mineral content (BMC), bone mineral density (BMD), and various biochemical markers of inflammation and bone metabolism in comparison to results obtained from: (1) RA patients who have not been treated with GCS and (2) the control group of healthy individuals. Sixty-two female patients with established active RA and 178 healthy individuals from the control group have been investigated. The RA patients were divided into three groups: 21 treated with GCS before the trial—these patients have continued GCS therapy using low doses during the observation; 21 with low-dose GCS therapy launched at the beginning of the trial; and 20 left without GCS treatment. All patients have been assessed twice: at the beginning and after 12 months of observation. BMC and BMD have been measured in all patients in a distal part of forearm. Additionally, several different biochemical markers of osteoporosis and inflammation have been determined.We did not notice any increase in bone metabolism between RA patients receiving GCS therapy for the first time and those treated without GCS after 12 months of observation. Results of BMC, BMD osteocalcin level, total and bone alkaline phosphatase, carboxy-terminal collagen cross links, carboxy-terminal propeptides of type 1 collagen, deoxypyridynoline, and calcium/creatinine ratio were comparable in both groups at the end of the study. There was a significant decrease of the level of IL-6 in patients who had GCS therapy launched at the beginning of observation (p < 0.01). However, levels of C-reactive protein (CRP) and α1-acid-glycoprotein (AGP) have not changed; the level of ESR dropped significantly (p < 0.05) in this group. In contrast, in the group of patients with the previous history of prolonged GCS treatment receiving low doses of GCS during the trial, statistically significant increase of CRP and AGP could be observed (p < 0.05) along with further significant worsening of the primary low BMD (p < 0.05).Based on the obtained data, we came to the conclusion that anti-inflammatory effect of the low-dose GCS therapy in RA patients without previous history of their use may balance their direct negative effect on BMC and BMD. In this group of RA patients, benefits resulting from the 12-month GCS therapy prevail over adverse effects, even if calcium with vitamin D3 supplementation, biphosphonians, or estrogens have not been introduced. On the other hand, low-dose GCS therapy could have no benefit for RA patients with the previous history of their prolonged use, as a rise of markers of inflammation and bone turnover, resulting in the further bone loss, has been observed.     

Use of recombinant activated factor VII in cardiac surgery for an effective treatment of severe intractable bleeding

Experience gained with administration of supranormal-therapeutic doses (90 microg/kg) of recombinant activated factor VII in 7 cardiac surgery patients is presented. The patients were given recombinant activated factor VII postoperatively for intractable bleeding, 5 of them after surgical revision. Administration of recombinant activated factor VII was associated with significant reduction in blood loss (P < 0.05) and shortening of INR and aPTT in laboratory tests. None of the patients needed reoperation. Administration of recombinant activated factor VII proved highly effective in management of massive hemorrhage in cardiac surgery.     

Impact of obesity on catheter ablation of atrial fibrillation: Patient characteristics,procedural complications,outcomes, and quality of life

Introduction

Obesity is a well-known risk factor for atrial fibrillation (AF). We aim to evaluate the effect of baseline obesity on procedural complications, AF recurrence, and symptoms following catheter ablation (CA).

Methods

All consecutive patients undergoing AF ablation (2013–2021) at our center were enrolled in a prospective registry. The study included all consecutive patients with available data on body mass index (BMI). Primary endpoint was AF recurrence based on electrocardiographic documentation. Patients were categorized into five groups according to their baseline BMI. Patients survey at baseline and at follow-up were used to calculate AF symptom severity score (AFSS) as well as AF burden (mean of AF duration score and AF frequency score; scale 0: no AF to 10: continuous and 9 frequencies/durations in between). Patients were scheduled for follow-up visits with 12-lead electrocardiogram at 3, 6, and 12 months after ablation, and every 6 months thereafter.

Results

A total of 5841 patients were included (17% normal weight, 34% overweight, 27% Class I, 13% Class II, and 9% Class III obesity). Major procedural complications were low (1.5%) among all BMI subgroups. At 3 years AF recurrence was the highest in Class III obesity patients (48%) followed by Class II (43%), whereas Class I, normal, and overweight had similar results with lower recurrence (35%). In multivariable analyses, Class III obesity (BMI ≥ 40) was independently associated with increased risk for AF recurrence (hazard ratio, 1.30; confidence interval, 1.06–1.60; p = .01), whereas other groups had similar risk in comparison to normal weight. Baseline AFSS was lowest in normal weight, and highest in Obesity-III, median (interquartile range) 10 (5–16) versus 15 (10–21). In all groups, CA resulted in a significant improvement in their AFSS with a similar magnitude among the groups. At follow-up, AF burden was minimal and did not differ significantly between the groups.

Conclusion

AF ablation is safe with a low complication rate across all BMI groups. Morbid obesity (BMI ≥ 40) was significantly associated with reduced AF ablation success. However, ablation resulted in improvement in QoL including reduction of the AFSS, and AF burden regardless of BMI.