Bertramhawley7168

Our multivariate analysis shows that only CTC presence is an independent risk factor associated with prostate cancer recurrence after prostatectomy (p less then 0.001). Our results suggest that CTC detection by ISET® before surgery is an interesting candidate predictive marker for cancer recurrence in patients with non-metastatic PCa.During the COVID-19 pandemic, several generic variants emerged, including the Alpha variant, with increased transmissibility compared to historical strains. We aimed to compare the evolution of the viral load between patients infected with the Alpha variant and those infected with the historical SARS-CoV-2 strains, while taking into account the time interval between the onset of symptoms and samples. We used data collected from patients with an acute respiratory infection (mild to moderate symptoms) and seen in consultation in primary care, included in a prospective longitudinal study, COVID-A. Patients performed four salivary samples during the follow-up. All patients who had at least one of the saliva samples test positive for SARS-CoV-2 were included in the analysis. Overall, 118 patients were included 89 infected by the historical strain and 29 infected by the Alpha variant. Even though we tended to observe a higher viral load in the Alpha variant group, we found no significant difference in the evolution of the viral load in saliva samples between patients infected with the Alpha variant of the SARS-CoV-2 and those infected by historical strains when controlling for the time interval between the onset of symptoms and sampling.Acclimation of cyanobacterium Synechocystis sp. PCC6803 to suboptimal conditions is largely dependent on adjustments of gene expression, which is highly controlled by the σ factor subunits of RNA polymerase (RNAP). The SigB and SigD σ factors are close homologues. Here we show that the sigB and sigD genes are both induced in high light and heat stresses. Comparison of transcriptomes of the control strain (CS), ΔsigB, ΔsigD, ΔsigBCE (containing SigD as the only functional group 2 σ factor), and ΔsigCDE (SigB as the only functional group 2 σ factor) strains in standard, high light, and high temperature conditions revealed that the SigB and SigD factors regulate different sets of genes and SigB and SigD regulons are highly dependent on stress conditions. The SigB regulon is bigger than the SigD regulon at high temperature, whereas, in high light, the SigD regulon is bigger than the SigB regulon. Furthermore, our results show that favoring the SigB or SigD factor by deleting other group 2 σ factors does not lead to superior acclimation to high light or high temperature, indicating that all group 2 σ factors play roles in the acclimation processes.The yeast Pichia pastoris was cultivated under different dissolved oxygen (DO) levels (5, 15, 30 and 50% of the air saturation) to evaluate its impact on the production of the cell-wall polysaccharide chitin-glucan complex (CGC) and mannans. Decreasing the DO level from 50 to 15% had no significant impact on cell growth but substrate conversion into biomass was improved. Under such conditions, a mannans content in the biomass of 22 wt% was reached, while the CGC content in the biomass was improved from 15 to 18 wt%, confirming that the DO level also impacted on P. pastoris cell-wall composition. Overall mannans and CGC volumetric productivity values of 10.69 and 8.67 g/(L. day) were reached, respectively. On the other hand, the polymers' composition was not significantly affected by decreasing the DO level. These results demonstrated that considerable energy savings can be made in the polysaccharide production process by reducing the DO level during cultivation of P. pastoris by improving the overall polymers' productivity without altering their composition. This has impact on the polysaccharide production costs, which is of considerable relevance for process scale-up and products' commercialization.B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The roles of B7-H3 in tumor progression make it a potential candidate for targeted therapy. Here, we generated a mouse anti-human B7-H3 antibody and demonstrated its binding activity via Tongji University Suzhou Instituteprotein-based and cell-based assays. We then developed a novel format anti-B7-H3 × anti-CD3 bispecific antibody based on the antibody-binding fragment of the anti-B7-H3 antibody and single-chain variable fragment structure of anti-CD3 antibody (OKT3) and demonstrated that this bispecific antibody mediated potent cytotoxic activities against various B7-H3-positive tumor cell lines in vitro by improving T cell activation and proliferation. This bispecific antibody also demonstrated potent antitumor activity in humanized mice xenograft models. These results revealed that the novel anti-B7-H3 × anti-CD3 bispecific antibody has the potential to be employed in treatment of B7-H3-positive solid tumors.The simultaneous cytological and metabolic investigation of various extravascular body fluids (EBFs) provides clinically relevant information about the type and intensity of the immune response in particular organ systems. The oxidative burst of professional phagocytes with the concomitant production of reactive oxygen species consumes a large amount of oxygen and is the cause of switch to the development of anaerobic metabolism. We assessed the relationships between percentages of neutrophils, aerobic and anaerobic metabolism, and tissue damage via the determination of aspartate aminotransferase catalytic activities (AST) in cerebrospinal fluid (CSF), pleural effusions (PE), abdominal effusions (AE), and synovial fluids (SF). EBFs with 0.0-20.0% neutrophils 83.0% aerobic and 1.3% strongly anaerobic cases with median of AST = 13.8 IU/L in CSF; 68.0% aerobic and 9.0% strongly anaerobic cases with median of AST = 20.4 IU/L in PE; 77.5% aerobic and 10.5% strongly anaerobic cases with median of AST = 18.0 IU/L in AE; 64.1% aerobic and 7.7% strongly anaerobic cases with median of AST = 13.8 IU/L in SF. EBFs with 80.0-100.0% neutrophils 4.2% aerobic and 73.7% strongly anaerobic cases with median of AST = 19.2 IU/L in CSF; 7.4% aerobic and 77.3% strongly anaerobic cases with median of AST = 145.2 IU/L in PE; 11.8% aerobic and 73.7% strongly anaerobic cases with median of AST = 61.8 IU/L in AE; 25.5% aerobic and 38.2% strongly anaerobic cases with median of AST = 37.2 IU/L in SF. The significant presence of neutrophils, concomitant strong anaerobic metabolism, and elevated AST in various EBFs are reliable signs of damaging purulent inflammation.We present our approach to rapidly establishing a standardized, multi-site, nation-wide COVID-19 screening program in Belgium. Under auspices of a federal government Task Force responsible for upscaling the country's testing capacity, we were able to set up a national testing initiative with readily available resources, putting in place a robust, validated, high-throughput, and decentralized qPCR molecular testing platform with embedded proficiency testing. We demonstrate how during an acute scarcity of equipment, kits, reagents, personnel, protective equipment, and sterile plastic supplies, we introduced an approach to rapidly build a reliable, validated, high-volume, high-confidence workflow based on heterogeneous instrumentation and diverse assays, assay components, and protocols. The workflow was set up with continuous quality control monitoring, tied together through a clinical-grade information management platform for automated data analysis, real-time result reporting across different participating sites, qc monitoring, and making result data available to the requesting physician and the patient. In this overview, we address challenges in optimizing high-throughput cross-laboratory workflows with minimal manual intervention through software, instrument and assay validation and standardization, and a process for harmonized result reporting and nation-level infection statistics monitoring across the disparate testing methodologies and workflows, necessitated by a rapid scale-up as a response to the pandemic.(1) Background Microorganisms originating from the microflora of the oral cavity are the main cause of the inflammatory diseases of the dental pulp and periapical periodontium, as well as the failure of endodontic treatment. The subsequent root canal treatment is not able to remove all the pathogens, and a small number of viable bacteria remain in the dentine tubules, which must be sealed by endodontic sealers. These sealers should have at least a bacteriostatic effect to prevent the remaining bacteria from reproducing. The aim of this study is to compare the short-term antibacterial activity of three endodontic sealers based on poly-epoxy resin, zinc oxide-eugenol and calcium silicate with a calcium hydroxide-based sealer. Calcium hydroxide is used as temporary intracanal medicament and, thus, should show significant antibacterial activity. (2) Methods A total of 25 bovine dentine samples infected with Enterococcus faecalis were used in this study. After the sealer placement and a 24 h incubation period, the root canal walls were scraped, and the suspension of dentine fillings was used for a semi-quantitative evaluation of microbial growth. (3) Results The poly-epoxide resin-based sealer ADSeal™ showed significant antibacterial properties. (4) Conclusions The highest antibacterial activity was shown in poly-epoxide resin-based sealer group, followed by the zinc oxide-eugenol-based sealer and calcium silicate-based sealer.Emerging and re-emerging zoonotic diseases cause serious illness with billions of cases, and millions of deaths. The most effective way to restrict the spread of zoonotic viruses among humans and animals and prevent disease is vaccination. Recombinant proteins produced in plants offer an alternative approach for the development of safe, effective, inexpensive candidate vaccines. Current strategies are focused on the production of highly immunogenic structural proteins, which mimic the organizations of the native virion but lack the viral genetic material. These include chimeric viral peptides, subunit virus proteins, and virus-like particles (VLPs). The latter, with their ability to self-assemble and thus resemble the form of virus particles, are gaining traction among plant-based candidate vaccines against many infectious diseases. In this review, we summarized the main zoonotic diseases and followed the progress in using plant expression systems for the production of recombinant proteins and VLPs used in the development of plant-based vaccines against zoonotic viruses.Despite its importance in intertidal and shallow-water marine ecosystems, Caprella penantis continues to be one of the most taxonomically challenging amphipods in the world. A recent molecular study focusing on C. penantis sensu stricto pointed out the existence of three highly divergent lineages, indicating the possible existence of a process of ongoing speciation and, thus, casting doubt on the taxonomic status of this species. In the present study, we used an integrative approach to continue to shed light on the taxonomy and distribution of this caprellid. To this end, we combined morphological and genetic data (COI and 18S) and included, for the first time, populations from its type locality. Our analyses provide strong evidence of the existence of potentially three distinct species, genetically and geographically restricted, within C. penantis sensu stricto, with the distribution of the true C. penantis sensu stricto restricted to the UK (type locality), the northern coast of the Iberian Peninsula, and the Azores. Results show the co-occurrence of two of these species in a locality of northern Portugal and indicate the existence of distinct evolutionary and diversification patterns along the eastern Atlantic region. Overall, our study highlights the use of an integrative approach to properly assess species boundaries and unravel hidden biodiversity in amphipods.Background Adequate perfusion of a bone flap is essential for successful reconstruction of osseous defects. Unfortunately, complications related to inadequate bone perfusion are common. Near-infrared fluorescence (NIRF) imaging enables intraoperative visualization of perfusion. NIRF has been investigated in reconstructive surgery to aid the surgeon in clinical perioperative assessment of soft tissue perfusion. However, little is known on the beneficial use of NIRF to assess bone perfusion. Therefore, the aim of this review was to search for studies evaluating NIRF to assess bone perfusion. Methods A systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, was performed. Studies up to October 2021 were included. We extracted data regarding the study population, size and design, reported objective fluorescence parameters and the methodology used for fluorescence imaging and processing. Results Ten articles were included. Studies reported unevenly on the protocol used for NIRF imaging. Five studies reported objective parameters. Absolute and relative perfusion parameters and parameters derived from maximum fluorescence were reported. The clinical significance of these parameters has not been evaluated in humans. Conclusion The evidence on bone perfusion as measured with NIRF is limited. More clinical studies are required.Management of patients with asthma during the coronavirus disease 2019 (COVID-19) pandemic is a concern, especially since asthma predisposes patients to respiratory problems. Interestingly, asthma characterized by type 2 inflammation, also known as T-helper type 2-high endotype, displays a cellular and molecular profile that may confer protective effects against COVID-19. The results of experimental and clinical studies have established the actions of immunoglobulin E (IgE) in inducing airway hyperreactivity and weakening an interferon-mediated antiviral response following respiratory viral infection. Robust evidence supports the beneficial effect of the anti-IgE biologic treatment omalizumab on reducing respiratory virus-induced asthma exacerbations and reducing the frequency, duration, and severity of respiratory viral illness in patients with asthma. Indeed, accumulating reports of patients with severe asthma treated with omalizumab during the pandemic have reassuringly shown that continuing omalizumab treatment during COVID-19 is safe, and in fact may help prevent the severe course of COVID-19. Accordingly, guidance issued by the Global Initiative for Asthma recommends that all patients with asthma continue taking their prescribed asthma medications, including biologic therapy, during the COVID-19 pandemic. The impact of biologic treatments on patients with asthma and COVID-19 will be better understood as more evidence emerges.Gut microbiota succession overlaps with intensive growth in infancy and early childhood. The multitude of functions performed by intestinal microbes, including participation in metabolic, hormonal, and immune pathways, makes the gut bacterial community an important player in cross-talk between intestinal processes and growth. Long-term disturbances in the colonization pattern may affect the growth trajectory, resulting in stunting or wasting. In this review, we summarize the evidence on the mediating role of gut microbiota in the mechanisms controlling the growth of children.Here we investigate protein levels in 69 multiple sclerosis (MS) cases and 143 healthy controls (HC) from twenty Sardinian families to search for promising biomarkers in plasma. Using antibody suspension bead array technology, the plasma levels of 56 MS-related proteins were obtained. Differences between MS cases and HC were estimated using Linear Mixed Models or Linear Quantile Mixed Models. The proportion of proteins level variability, explained by a set of 119 MS-risk SNPs as to the literature, was also quantified. Higher plasma C9 and CYP24A1 levels were found in MS cases compared to HC (p less then 0.05 after Holm multiple testing correction), with protein level differences estimated as, respectively, 0.53 (95% CI 0.25, 0.81) and 0.42 (95% CI 0.19, 0.65) times plasma level standard deviation measured in HC. Furthermore, C9 resulted in both statistically significantly higher relapsing-remitting MS (RRMS) and secondary-progressive MS (SPMS) compared to HC, with SPMS showing the highest differences. Instead, CYP24A1 was statistically significantly higher only in RRMS as compared to HC. Respectively, 26% (95% CI 10%, 44%) and 16% (95% CI 9%, 39%) of CYP24A1 and C9 plasma level variability was explained by known MS-risk SNPs. Our results highlight C9 and CYP24A1 as potential biomarkers in plasma for MS and allow us to gain insight into molecular disease mechanisms.Oral carcinogenesis is a multistep process. As much as 5% to 85% of oral tumors can develop from potentially malignant disorders (PMD). Although the oral cavity is accessible for visual examination, the ability of current clinical or histological methods to predict the lesions that can progress to malignancy is limited. Thus, developing biological markers that will serve as an adjunct to histodiagnosis has become essential. Our previous studies comprehensively demonstrated that aberrant vimentin expression in oral premalignant lesions correlates to the degree of malignancy. Likewise, overwhelming research from various groups show a substantial contribution of vimentin in oral cancer progression. In this review, we have described studies on vimentin in oral cancers, to make a compelling case for vimentin as a prognostic biomarker.

Primary (familial) hemophagocytic lymphohistiocytosis (pHLH) is a potentially lethal syndrome of infancy, caused by genetic defects in natural killer (NK) cell and CD8 T cell cytotoxicity, leading to hyperinflammation, elevated cytokine levels, and a disorganized immune response resulting in multi-organ system failure and frequently death. Secondary HLH (sHLH) can be triggered in the setting of malignances, diseases of chronic immune system activation, or by infectious etiologies. While pHLH is usually a result of homozygous gene mutations, monoallelic hypomorphic and dominant-negative mutations in pHLH genes have been implicated in sHLH. Coronavirus disease 2019 (COVID-19) has been an omnipresent viral infection since its arrival, and severe cases can present with cytokine storm and have clinical features and laboratory findings consistent with sHLH. Herein, we report an adolescent with severe COVID-19, decreased NK cell function, and features of sHLH. Her genetic evaluation identified a monoallelic missenesis that some severe cases of COVID-19 may be accompanied by sHLH and hyperinflammation, especially in the setting of heterozygous pHLH genetic mutations. This has implications both diagnostically and therapeutically for severe COVID-19.Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients' exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the retween mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p less then 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.Wastewater is considered the most serious source of the spread of antibiotic resistance in the environment. This work, therefore, focuses on the fate and spread of antibiotic resistance genes (ARGs) in wastewater and the monitoring of multidrug-resistant strains. ARGs were monitored in the nitrification and sedimentation tanks of the wastewater treatment plant (WWTP) and in the dam into which this WWTP flows, at various times. The highest relative abundance was found for the blaTEM > tetW > blaNDM-1 > vanA resistance genes, respectively. An increased concentration of tetracycline (up to 96.00 ng/L) and ampicillin (up to 19.00 ng/L) was found in water samples compared to other antibiotics detected. The increased incidence of seven ARGs and four antibiotics was observed in the November and December sampling times. Isolated ampicillin-resistant strains showed a high degree of resistance to ampicillin (61.2% of the total isolates had a minimum inhibitory concentration (MIC) ≥ 20 mg/mL). In 87.8% of isolates, out of the total number, the occurrence of two or more ARGs was confirmed. These multidrug-resistant strains were most often identified as Aeromonas sp. This strain could represent a significant role in the spread of multidrug resistance through wastewater in the environment.Cerebral adrenoleukodystrophy (ALD) is a rare neuroinflammatory disorder characterized by progressive demyelination. Mutations within the ABCD1 gene result in very long-chain fatty acid (VLCFA) accumulation within the peroxisome, particularly in the brain. While this VLCFA accumulation is known to be the driving cause of the disease, oxidative stress can be a contributing factor. For patients with early cerebral disease, allogeneic hematopoietic stem cell transplantation (HSCT) is the standard of care, and this can be supported by antioxidants. To evaluate the involvement of fatty acid oxidation in the disease, F2-isoprostanes (F2-IsoPs), F2-dihomo-isoprostanes (F2-dihomo-IsoPs) and F4-neuroprostanes (F4-NeuroPs)-which are oxygenated metabolites of arachidonic (ARA), adrenic (AdA) and docosahexaenoic (DHA) acids, respectively-in plasma samples from ALD subjects (n = 20)-with various phenotypes of the disease-were measured. Three ALD groups were classified according to patients with (1) confirmed diagnosis of plasma amounts of all investigated isoprostanoids were shown to discriminate ALD patients vs. healthy subjects. Altogether, isoprostanoids are relevant to the phenotype of X-ALD and may be helpful in predicting the presence of cerebral disease and establishing the risk of progression.Recently, an evolution experiment was carried out in a cyclic process, which involved periodic vesicle formation in combination with peptide and vesicle selection. As an outcome, an octapeptide (KSPFPFAA) was identified which rapidly integrated into the vesicle membrane and, according to its significant accumulation, is obviously connected to a particular advantage of the corresponding functionalized vesicle. Here we report a molecular dynamics study of the structural details of the functionalized vesicle membrane, which was a product of this evolution process and is connected to several survival mechanisms. In order to elucidate the particular advantage of this structure, we performed all-atom molecular dynamics simulations to examine structural changes and interactions of the peptide (KSPFPFAA) with the given octadecanoic acid/octadecylamine (11) bilayer under acidic conditions. The calculations clearly demonstrate the specific interactions between the peptide and the membrane and reveal the mechanisms leading to the improved vesicle survival.One of the major concerns for long-term exploration missions beyond the Earth's magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will provide both nutritional supplements and psychological benefits to the astronauts. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of two different compositions of charged particles-simulated GCR, and simulated SPE protons on dry and hydrated seeds of the model plant Arabidopsis thaliana and the crop plant Mizuna mustard [Brassica rapa var. japonica]. Exposures to charged particles, simulated GCRs (up to 80 cGy) or SPEs (up to 200 cGy), were performed either acutely or at a low dose rate using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Control and irradiated seeds were planted in a solid phytogel and grown in a controlled environment. Five to seven days after planting, morphological parameters were measured to evaluate radiation-induced damage in the seedlings. After exposure to single types of charged particles, as well as to simulated GCR, the hydrated Arabidopsis seeds showed dose- and quality-dependent responses, with heavier ions causing more severe defects. Seeds exposed to simulated GCR (dry seeds) and SPE (hydrated seeds) had significant, although much less damage than seeds exposed to heavier and higher linear energy transfer (LET) particles. In general, the extent of damage depends on the seed type.Drug addiction has become a worldwide problem, affecting millions of people across the globe. While the majority of mechanistic studies on drug addiction have been focused on the central nervous system, including the mesolimbic dopamine system, the peripheral actions of drugs of abuse remain largely unknown. Our preliminary study found that the systemic injection of cocaine increased peripheral skin temperature. This led us to our present study, which investigated the mechanisms underlying the increase in peripheral temperature following cocaine injection. Male Sprague Dawley rats were anesthetized with pentobarbital sodium, and peripheral skin temperature measurements were taken using a thermocouple needle microprobe and an infrared thermal camera. Cocaine injection caused an acute rise in peripheral body temperature, but not core body temperature, about 10 min after injection, and the temperature increases were occluded by systemic injection of dopamine D2 receptor antagonist L741,626, but not D1 receptor antagonist SCH23390. In addition, systemic administration of bromocriptine, a dopamine D2 receptor agonist, significantly increased peripheral temperature. Infrared thermal imaging showed that the thermal increases following cocaine injection were predominantly in the distal areas of the forelimbs and hindlimbs, relative to core body temperature. Treatment with cocaine or bromocriptine decreased the size of skin blood vessels without affecting the expression of dopamine D2 receptors. These results suggest that increased peripheral temperature in skin following cocaine injection is associated with the activation of the dopamine D2 receptor.Headache is the most frequent neurological symptom in childhood and the main reason for admission to pediatric emergency departments. The aim of this consensus document is to define a shared clinical pathway between primary care pediatricians (PCP) and hospitals for the management of children presenting with headache. For the purposes of the study, a group of hospital pediatricians and a group of PCP from the Emilia Romagna's health districts were selected to achieve consensus using the RAND/UCLA appropriateness method. Thirty-nine clinical scenarios were developed for each scenario, participants were asked to rank the appropriateness of each option from 1 to 9. Agreement was reached if ≥75% of participants ranked within the same range of appropriateness. The answers, results, and discussion helped to define the appropriateness of procedures with a low level of evidence regarding different steps of the diagnostic-therapeutic process primary care evaluation, emergency department evaluation, hospital admission, acute therapy, prophylaxis, and follow-up. The RAND proved to be a valid method to value appropriateness of procedures and define a diagnostic-therapeutic pathway suitable to the local reality in the management of pediatric headache. From our results, some useful recommendations were developed for optimizing the healthcare professionals' network among primary care services and hospitals.(1) Background Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

The 'speed bump sign' is a clinical symptom characterised by aggravated abdominal pain while driving over speed bumps. This study aimed to perform a diagnostic meta-analysis, rate the certainty of evidence (CoE) and analyse the applicability of the speed bump sign in the diagnosis of acute appendicitis.

Four databanks and websites were systemically searched, and the Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias. Meta-analysis was assessed by MIDAS commands in Stata 15. Grading of Recommendations, Assessment, Development and Evaluation methodology was applied to examine the CoE.

Four studies with 343 participants were included. The pooled sensitivity and specificity were 0.94 (95% CI (confidence interval) = 0.83-0.98; I

= 79%) and 0.49 (95% CI = 0.33-0.66; I

= 67%), respectively. The area under the summary receiver operating characteristic curve was 0.78 (95% CI = 0.74-0.81). The diagnostic odds ratio was 14.1 (95% CI = 3.6-55.7). The pooled positive and negative likelihood ratios (LR (+) and LR (-)) were 1.84 (95% CI = 1.30-2.61) and 0.13 (95% CI = 0.04-0.41), respectively. According to Fagan's nomogram plot, when the pretest probabilities were 25%, 50% and 75%, the related posttest probabilities increased to 38%, 65% and 85% calculated through LR (+), respectively, and the posttest probabilities were 4%, 12% and 28% calculated through LR (-), respectively. The overall CoEs were low and very low in sensitivity and specificity, respectively.

Current evidence shows that the speed bump sign is a useful 'rule-out' test for diagnosing acute appendicitis. With good accessibility, the speed bump sign may be added as a routine part of taking the history of patients with abdominal pain.

Current evidence shows that the speed bump sign is a useful 'rule-out' test for diagnosing acute appendicitis. With good accessibility, the speed bump sign may be added as a routine part of taking the history of patients with abdominal pain.Elastin-like polypeptides (ELPs) are soluble in water at low temperature, but, on increasing the temperature, they undergo a reversible and cooperative, coil-to-globule collapse transition. It has been shown that the addition to water of either trimethylamine N-oxide (TMAO), glycine, or betaine causes a significant decrease of T(collapse) in the case of a specific ELP. Traditional rationalizations of these phenomena do not work in the present case. We show that an alternative approach, grounded in the magnitude of the solvent-excluded volume effect and its temperature dependence (strictly linked to the translational entropy of solvent and co-solute molecules), is able to rationalize the occurrence of ELP collapse in water on raising the temperature, as well as the T(collapse) lowering caused by the addition to water of either TMAO, glycine, or betaine.

Numerous cyanobacteria have the potential to reduce metallic ions to form pure metal nanoparticles in a green biosynthesis process.

To investigate the production capacity of silver nanoparticles by the cyanobacterium

sp. and to examine the effect of five different phytohormones, indole acetic acid, kinetin; gibberellic acid; abscisic acid; and methyl jasmonate, on this capacity.

The cyanobacterial strain was grown for 60 days and the harvested cyanobacterium biomass was incubated with 0.1 mM of AgNO

. Percentage conversion of Ag

to Ag

was calculated to indicate the AgNPs' production capacity. Different concentrations of the five phytohormones were added to cultures and the AgNP production was monitored throughout different time intervals.

sp. biosynthesized spherical AgNPs (diameter range 70 to 140 nm, average diameter 84.37 nm). The addition of indole acetic acid and kinetin provoked the maximum conversion (87.29% and 55.16%, respectively) of Ag

to Ag

, exceeding or slightly below that of the control (56%). Gibberellic and abscisic acids failed to elevate the Ag

to Ag

conversion rate (45.23% and 47.95%, respectively) above that of the control. Methyl jasmonate increased the Ag

to Ag

conversion rate to 90.29%, although nearly all the cyanobacterial cultures died at the end.

Phytohormones could be used to induce or inhibit the green production of AgNPs with the cyanobacterium

sp. This novel manipulation technique may have several applications in agriculture or biomedicine.

Phytohormones could be used to induce or inhibit the green production of AgNPs with the cyanobacterium Cyanothece sp. This novel manipulation technique may have several applications in agriculture or biomedicine.The Bonebridge implant can be a satisfactory solution for patients with conductive or mixed hearing loss (CHL or MHL), or with single-sided deafness (SSD). The aim of the study was to assess patients' self-reported benefits with the Bonebridge and characterize the relationships between pre-implantation audiometric data, auditory functioning, and satisfaction after implantation. A focus was to see whether different types of hearing loss were associated with particular benefits. The study sample consisted of 81 patients. Procedures comprised pure tone audiometry before implantation, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, and a structured interview asking about satisfaction. Statistically significant improvements after implantation were found in all groups (CHL, MHL, SSD) on the APHAB questionnaire. In the structured interview, patients with SSD were the least satisfied. No significant correlation was found between pre-operative air-bone gap and bone conduction thresholds or with APHAB score. Bonebridge implantation is beneficial to patients with CHL or MHL, or with SSD. Assessment of patients for Bonebridge implantation is complex, and audiometric data should be complemented by patient-reported outcomes to provide deeper insight into their individual needs and attitudes.This review asks some hard questions about what the enigmatic graphoglyptid trace fossils are, documents some of their early fossil record from the Ediacaran-Cambrian transition and explores the idea that they may not have been fossils at all. Most researchers have considered the Graphoglyptida to have had a microbial-farming mode of life similar to that proposed for the fractal Ediacaran Rangeomorpha. This begs the question "What are the Graphoglyptida if not the Rangeomorpha persevering" and if so then "What if…?". This provocative idea has at its roots some fundamental questions about how to distinguish burrows sensu-stricto from the external molds of endobenthic sediment displacive organisms.

Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns.

This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect as the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.

Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db-/db-) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. Mmp3, Mmp9, Mmp13 and gene expression of MMP inhibitor Timp2 was significantly higher in regenerating bone fractures of db-/db- compared to wild type animals. Timp1 and metalloproteinase AdamTS4 showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db-/db-. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db-/db- were restored significantly by application of Marimastat compared to PBS controls (n = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes.

While congenital choledochal malformation (CCM) is relatively well known within the pediatric surgical and pediatric gastroenterological communities, many controversies and questions remain.

In this paper, we will discuss the results of an international Delphi survey among members of the European Reference Network RARE-LIVER and of the faculty of the Biliary Atresia and Related Diseases (BARD) network to identify the most common practices as well as controversies regarding diagnosis, treatment and follow-up of this still enigmatic disease.

Twenty-two individual respondents completed the survey. While there seems to be agreement on the definitions of CCM, preoperative workup, surgical approach and follow-up still vary considerably. The mainstay of treatment remains the removal of the entire extrahepatic biliary tract, clearance of debris both proximally and distally, followed by reconstruction with (according to 86% of respondents) a Roux-en-Y hepaticojejunostomy. Nonetheless, both laparoscopic and robotic-assisted resections are gaining ground with the suggestion that this might be facilitated by concentration of care and resources in specialized centers. However, long-term outcomes are still lacking.

As even post-surgical CCM has to be considered as having premalignant potential, follow-up should be well-organized and continued into adulthood. This seems to be lacking in many centers. International cooperation for both benchmarking and research is paramount to improving care for this rare disease.

As even post-surgical CCM has to be considered as having premalignant potential, follow-up should be well-organized and continued into adulthood. This seems to be lacking in many centers. International cooperation for both benchmarking and research is paramount to improving care for this rare disease.Ahyahuasca is a term commonly used to describe a decoction prepared by cooking the bark or crushed stems of the liana Banisteriopsis caapi (contains β-carbolines) alone or in combination with other plants, most commonly leaves of the shrub Psychotria viridis (contains N,N-dimethyltryptamine-DMT). More than 100 different plants can serve as sources of β-carbolines and DMT, which are the active alkaloids of this decoction, and therefore it is important to know the most accurate composition of the decoction, especially when studying the pharmacology of this plant. The aim was to summarize the latest sensitive methods used in the analysis of the composition of the beverage itself and the analysis of various biological matrices. We compared pharmacokinetic parameters in all of the studies where decoction of ayahuasca was administered and where its composition was known, whereby minimal adverse effects were observed. The therapeutic benefit of this plant is still unclear in the scientific literature, and side effects occur probably on the basis of pre-existing psychiatric disorder. We also described toxicological risks and clinical benefits of ayahuasca intake, which meant that the concentrations of active alkaloids in the decoction or in the organism, often not determined in publications, were required for sufficient evaluation of its effect on the organism. We did not find any post-mortem study, in which the toxicological examination of biological materials together with the autopsy findings would suggest potential lethality of this plant.The elimination of viral hepatitis in target populations is crucial in reaching WHO viral hepatitis elimination goals. Several barriers for the treatment of viral hepatitis in people with addictive disorders have been identified, yet nationwide data on hepatitis healthcare utilization (HCU) in these patients are limited. We investigated whether a history of addictive disorder is associated with suboptimal hepatitis HCU, indicating failure to receive diagnostic care or treatment. We identified all newly referred viral hepatitis patients in the Netherlands between 2014 and 2019 by query of the Dutch national hospital claims database. Each patient's first year of HBV or HCV care activities was collected and clustered in two categories, 'optimal' or 'suboptimal' hepatitis HCU. Optimal HCU includes antiviral therapy. We tested the association between addiction history and HCU, adjusted for sex, age, migrant status, and comorbidity. In secondary analyses, we explored additional factors affecting hepatitis HCU. We included 10,513 incident HBV and HCV patients, with 13% having an addiction history. Only 47% of all patients achieved optimal hepatitis HCU. Addiction history was associated with less suboptimal HCU (adjusted OR = 0.73, 95% CI = 0.64-0.82). Migration background was associated with suboptimal HCU (OR = 1.62, 95% CI = 1.50-1.76). This study shows that addiction history is associated with higher viral hepatitis HCU; thus, this population performs better compared to non-addicted patients. However, less than 50% of all patients received optimal hepatitis care. This study highlights the need to improve hepatitis HCU in all patients, with a focus on migrant populations. Linkage to care in the addicted patients is not studied here and may be a remaining obstacle to be studied and improved to reach WHO viral hepatitis elimination goals.(1) Background Measles immunization gap(s) raise the concern of potential outbreaks. Both Croatia and Hungary are situated in the vicinity of measles-endemic countries. Potentially compromised immunization activities due to the COVID-19 surge is a ground for concern. Our aim was to compare age-stratified seroprevalence results in the cross-border region. (2) Methods Anti-MMR specific antibody levels (IgG) of 950 anonymous Croatian samples were compared with previous Hungarian results (n > 3500 samples), and former Croatian seroprevalence data (n = 1205). Seropositivity ratios were determined using our self-developed anti-MMR indirect ELISA (Euroimmun IgG ELISA kits were used as control). (3) Results Measured seropositivity ratios of the Croatian samples were largely overlapping with our earlier published Hungarian data (the lowest seropositivity ratios were measured among individuals of 34-43 years of age with 78% of seropositivity) and are in accordance with earlier published data of Croatian researchers. (4) Conclusion Although the epidemiological histories of the two countries are different, analogies in age-specific measles susceptibility have been discovered. We suggest that besides the potential coincidence in vaccination ineffectiveness, the inherent biological dynamics of vaccination-based humoral protection might have also contributed to the experienced similarities. Our findings may also serve as a lesson regarding the current anti-COVID-19 vaccination strategy.

Plasma cell-free Deoxyribo nucleic acid epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC.

In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction.

The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days,

< 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group.

Smoking status and the factors reflecting tumor burden were associated with the detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.

Smoking status and the factors reflecting tumor burden were associated with the detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.Bladder cancers have high recurrence rates and are usually removed via transurethral resection of bladder tumor (TURBT). Recently, some reports showed that the anesthetic method may affect the recurrence rates of bladder cancers. The purpose of this population-based study was to compare the effect of anesthetic methods with the recurrence rates of bladder cancers in South Korea. A total of 4439 patients were reviewed retrospectively using the data of the Korean National Health Insurance (NHI) claims database from January 2007 to December 2011. Patients were divided into 2 groups who received general (n = 3767) and regional anesthesia (n = 582), and were followed up until September 2017. Propensity score matching was conducted to reduce the effect of confounding factors. After using propensity score matching with a multivariable Cox regression model, age (p less then 0.001), sex (p less then 0.001), hypertension (p = 0.003), diabetes mellitus (p = 0.001), and renal disease (p less then 0.001) were significantly associated with bladder cancer recurrence. However, there were no significant differences in the recurrence rates of bladder cancers in patients who received general anesthesia and spinal anesthesia for TURBTs. This study revealed that there is no relationship between the anesthetic method and bladder cancer recurrence. Either general anesthesia or regional anesthesia can be used depending on the situation in patients receiving TURBT. Future prospective studies are warranted to confirm the association between the anesthetic method and the recurrence rates of bladder cancer.Background Survivors of sepsis often face long-term sequelae after intensive care treatment. Compared to the period of hospitalization, little is known about the ambulatory healthcare utilization in sepsis patients. The study evaluated healthcare utilization and associated costs of sepsis care including allied health professions after initial hospitalization. Methods Secondary analysis was performed on data in 210 sepsis patients prospectively enrolled from nine intensive care study centers across Germany. Data was collected via structured surveys among their Primary care (Family-) physicians (PCPs) within the first month after discharge from ICU (baseline) and again at 6, 12 and 24 months after discharge, each relating to the period following the last survey. Costs were assessed by standardized cost unit rates from a health care system's perspective. Changes in healthcare utilization and costs over time were calculated using the Wilcoxon rank-sum test. Results Of the 210 patients enrolled, 146 (69.5%) patients completed the 24 months follow-up.