Patients' expectations surrounding revision total hip arthroplasty: a literature review.

BACKGROUND: Revision total hip arthroplasties (RTHA) are associated with a higher complication rate than primary total hip arthroplasties (THA), and therefore it is important for patients to have realistic expectations regarding outcomes. The aim of this literature review was to gather and summarize the available evidence on patients' expectations following RTHA. METHODS: A literature search was conducted in PubMed, PsycINFO, Cochrane, Google Scholar, Web of Science and Embase from inception to November 2023. Articles assessing patient expectations for RTHA were included. Methodological quality was assessed by two independent reviewers using the National Heart, Lung and Blood Institute (NIH) study quality assessment tool for observational cohort and cross-sectional studies. A qualitative analysis was performed involving the summarization of study characteristics and outcomes. RESULTS: The search strategy generated 7,450 references, of which 5 articles met the inclusion criteria. Methodological quality scores ranged from 7-10. Patients had high expectations concerning future walking ability, pain and implant longevity relative to actual postoperative outcomes. A significant positive correlation was found between fulfilled expectations of pain and walking ability and patient satisfaction (r = 0.46-0.47). Only two studies assessed the fulfillment of patient expectations. Great variability was seen in the measurement of expectations. CONCLUSION: Patients undergoing RTHA appeared to have high expectations for pain and functionality compared to postoperative outcomes. However, there was a paucity of high-quality data in this area, limiting the accuracy of the conclusion. Further research is needed, that emphasizes developing a sound theoretical framework for expectations, allowing for the consistent implementation of valid measurement tools for patient expectations.

Prevalence of persistent SARS-CoV-2 in a large community surveillance study.

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

HLD-DDoSDN: High and low-rates dataset-based DDoS attacks against SDN.

Software Defined Network (SDN) has alleviated traditional network limitations but faces a significant challenge due to the risk of Distributed Denial of Service (DDoS) attacks against an SDN controller, with current detection methods lacking evaluation on unrealistic SDN datasets and standard DDoS attacks (i.e., high-rate DDoS attack). Therefore, a realistic dataset called HLD-DDoSDN is introduced, encompassing prevalent DDoS attacks specifically aimed at an SDN controller, such as User Internet Control Message Protocol (ICMP), Transmission Control Protocol (TCP), and User Datagram Protocol (UDP). This SDN dataset also incorporates diverse levels of traffic fluctuations, representing different traffic variation rates (i.e., high and low rates) in DDoS attacks. It is qualitatively compared to existing SDN datasets and quantitatively evaluated across all eight scenarios to ensure its superiority. Furthermore, it fulfils the requirements of a benchmark dataset in terms of size, variety of attacks and scenarios, with significant features that highly contribute to detecting realistic SDN attacks. The features of HLD-DDoSDN are evaluated using a Deep Multilayer Perception (D-MLP) based detection approach. Experimental findings indicate that the employed features exhibit high performance in the detection accuracy, recall, and precision of detecting high and low-rate DDoS flooding attacks.

Assessing disparities in medical students' knowledge and attitude about monkeypox: a cross-sectional study of 27 countries across three continents.

Background and aims: The recent monkeypox (Mpox) outbreak confirmed by the World Health Organization (WHO) underscores the importance of evaluating the knowledge and attitude of medical students toward emerging diseases, given their potential roles as healthcare professionals and sources of public information during outbreaks. This study aimed to assess medical students' knowledge and attitude about Mpox and to identify factors affecting their level of knowledge and attitude in low-income and high-income countries. Methods: A cross-sectional study was conducted on 11,919 medical students from 27 countries. A newly-developed validated questionnaire was used to collect data on knowledge (14 items), attitude (12 items), and baseline criteria. The relationship between a range of factors with knowledge and attitude was studied using univariate and multivariate analyses. Results: 46% of the study participants were males; 10.7% were in their sixth year; 54.6% knew about smallpox; 84% received the coronavirus disease 2019 (COVID-19) vaccine; and 12.5% had training on Mpox. 55.3% had good knowledge of Mpox and 51.7% had a positive attitude towards it. Medical students in their third, fifth, or sixth year high- income countries who obtained information on Mpox from friends, research articles, social media and scientific websites were positive predictors for good knowledge. Conversely, being male or coming from high-income countries showed a negative relation with good knowledge about Mpox. Additionally, a positive attitude was directly influenced by residing in urban areas, being in the fifth year of medical education, having knowledge about smallpox and a history of receiving the coronavirus disease 2019 (COVID-19) vaccine. Receiving information about Mpox from social media or scientific websites and possessing good knowledge about Mpox were also predictors of a positive attitude. On the other hand, being male, employed, or receiving a training program about Mpox were inversely predicting positive attitude about Mpox. Conclusion: There were differences in knowledge and attitude towards Mpox between medical students in low and high-income countries, emphasizing the need for incorporating epidemiology of re-emerging diseases like Mpox into the medical curriculum to improve disease prevention and control.

Corrigendum: Factors influencing participation in COVID-19 clinical trials: a multinational study.

[This corrects the article DOI: 10.3389/fmed.2021.608959.].

Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines.

Developing a safe and effective preventive for HIV-1 remains the hope for controlling the global AIDS epidemic. Recently, mRNA vaccines have emerged as a promising alternative to conventional vaccine approaches, primarily due to their rapid development and potential for low-cost manufacture. Despite the advantages of mRNA vaccines, challenges remain, especially due to the adverse effects of the delivery vehicle and low delivery efficiency. As a result, Luna Labs is developing a short carbon nanotube-based delivery platform (NanoVac) that can co-deliver mRNA and HIV-1 glycoproteins to the immune system efficiently with negligible toxicity. Surface chemistries of NanoVac were optimized to guide antigen/mRNA loading density and presentation. Multiple formulations were engineered for compatibility with both intramuscular and intranasal administration. NanoVac candidates demonstrated immunogenicity in rabbits and generated human-derived humoral and cellular responses in humanized mice (HIS). Briefly, 33% of the HIV-1-infected HIS mice vaccinated with NanoVac-mRNA was cleared of virus infection by 8-weeks post-infection. Finally, NanoVac stabilized the loaded mRNA against degradation under refrigeration for at least three months, reducing the cold chain burden for vaccine deployment.

The sensitivity of TIRADS scoring on ultrasonography in the management of thyroid nodules.

Objective: To determine the sensitivity of ACR-TIRADS scoring by comparing its results with those obtained on biopsy of respective specimens. Method: This prospective study including N=205 patients with thyroid nodules was conducted in ENT Department of MTI Hayatabad Medical complex, Peshawar during the period from May 1, 2019 to April 30, 2022. Preoperative ultrasonography with assigning of TIRADS scores was performed in all patients. Appropriate thyroidectomies were performed in these patients and specimen biopsied. Pre-op TIRADS scores were compared with biopsy results. To determine the sensitivity of TIRADS, TR1 and TR2 were considered 'benign' and TR3, TR4, TR5 were considered 'malignant' for comparison with biopsy results. Results: The mean age of patients was 37.68 years with standard deviation of ±11.52. The M: F ratio was 1:3.5. Nineteen patients (9.27%) had solitary thyroid nodules & 186 (90.73%) had multinodular goiters. TIRADS scoring was benign for 171 (83.41%) and malignant for 34 (16.58%) nodules. The biopsy results revealed 180 (87.80%) nodules to benign and the rest as malignant. The sensitivity, specificity and diagnostic accuracy were calculated at 80%, 92.77% and 91.21% respectively. Chi square test and p-value determination showed that there was a strong positive concordance between TIRADS scores & biopsy results which is highly significant (p=.001). Conclusion: The Ultrasonographic ACR-TIRADS scoring and risk stratification system is highly sensitive for detecting malignancy in thyroid nodules. It is, therefore, a reliable technique in the initial assessment of thyroid nodules and decisions can safely be based on its results. In cases of doubt, clinical judgment should be exercised before making final decision.

A Systematic Literature Review on Machine Learning and Deep Learning Approaches for Detecting DDoS Attacks in Software-Defined Networking.

Software-defined networking (SDN) is a revolutionary innovation in network technology with many desirable features, including flexibility and manageability. Despite those advantages, SDN is vulnerable to distributed denial of service (DDoS), which constitutes a significant threat due to its impact on the SDN network. Despite many security approaches to detect DDoS attacks, it remains an open research challenge. Therefore, this study presents a systematic literature review (SLR) to systematically investigate and critically analyze the existing DDoS attack approaches based on machine learning (ML), deep learning (DL), or hybrid approaches published between 2014 and 2022. We followed a predefined SLR protocol in two stages on eight online databases to comprehensively cover relevant studies. The two stages involve automatic and manual searching, resulting in 70 studies being identified as definitive primary studies. The trend indicates that the number of studies on SDN DDoS attacks has increased dramatically in the last few years. The analysis showed that the existing detection approaches primarily utilize ensemble, hybrid, and single ML-DL. Private synthetic datasets, followed by unrealistic datasets, are the most frequently used to evaluate those approaches. In addition, the review argues that the limited literature studies demand additional focus on resolving the remaining challenges and open issues stated in this SLR.

Mechanical and antibacterial properties of conventional pit and fissure sealants with addition of miswak fibers.

The occlusal surface of a tooth is affected by the development of biofilm in pits and fissures as bacteria and food particles accumulate in its complex structure. In this study, miswak fibers containing cellulose and antimicrobial extract were incorporated in commercial pit and fissure sealants. The miswak powder was characterized by different analytical techniques. The powder was mixed in different ratios (0-5%) into a pit and fissure sealant to result in five sealants (Groups 0-5), and their mechanical properties i.e. flexural strength, compressive strength, and Vickers hardness were evaluated. The sealants were also evaluated against streptococcus mutans oral pathogenic bacteria. SEM analysis confirmed irregular shape and micron-size particles of miswak powder. The infrared spectral analysis and X-ray differential peaks showed characteristic peaks related to miswak fibers. The particle appearance increased in prepared pits and fissure sealants with higher loading of miswak powder in SEM analysis. The flexural strength, compressive strength, and Vickers hardness values were obtained in the range of 148-221 (±16.6: p-value < 0.001) MPa, 43.1-50.3 MPa (±1.7: p-value <0.001), and 15.2-21.26 VHN (±0.56: p-value <0.001) for control and prepared sealant specimens respectively. In the antibacterial study, the zone of inhibitions increased with increased content of miswak from 15.6 ± 0.45 mm (Group 1) to 20.3 ± 0.32 mm (Group 5). The MIC was calculated to be 0.039%. The prepared experimental sealant had acceptable mechanical and good antibacterial properties therefore it could be recommended as an efficient pit and fissure sealant.

Excitation wavelength-dependent photoluminescence decay of single quantum dots near plasmonic gold nanoparticles.

Changing the excitation wavelength is a simple but effective strategy to modulate the photophysical cha racteristics of colloidal quantum dots (QDs) near plasmonic nanostructures. It has been observed that the photoluminescence (PL) decay of QDs near plasmonic nanostructures differs when the excitation wavelength is varied, but the exact mechanism is still unclear today. Here, we studied the excitation wavelength dependence of the PL decay of CdSe/CdS core/shell QDs near plasmonic gold nanoparticles at the single QD level. With the aid of statistical science, we demonstrated that the PL decay of a single QD near gold nanoparticles is generally faster when the QD is excited spectrally close to the localized surface plasmon resonance of gold nanoparticles. This excitation wavelength dependence is mainly caused by the varied proportion of photons coming from biexciton emission, which is the result of different local electric field enhancement by gold nanoparticles upon excitation.

Antibody Response to SARS-CoV-2 in Relation to the Contributing Factors in COVID-19 Patients.

Human health has always been challenged by variety of viral infections, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has surpassed all previous viral diseases and emerged as a major health challenge around the globe. Real-time polymerase chain reaction (PCR) is the gold standard for the diagnosis of SARS-CoV-2 and serological assay provides a compliment to diagnosis after second week of infection. The aim of the study is the characterization of antibody response to SARS-CoV-2 in the blood sample of diagnosed coronavirus disease 2019 (COVID-19) patients, and its potential association with factors such as age, gender, time, and symptoms. Serum from 248 confirmed SARS-CoV-2 patients was investigated for antibodies. Elecsys anti-SARS chemiluminescent immune assay was performed for the detection of nucleocapsid-specific antibodies. Association of antibody response with gender, age, and time after onset of symptoms was analyzed. Among 248 PCR positive SARS-CoV-2 patients, 214 (86.3%) have virus-specific antibody signals. Antibodies positivity rate was higher in male patient patients as compared with female patients (90.8% vs. 79.2%, p = 0.009). Patients aged 30-40 years had the highest antibody positivity rate as compared with other groups (89.10%, p = 0.04). Patients age group >60 years had a lower positivity rate (75%, p = 0.04). The increasing trend in the antibodies detection with time was observed, maximum positive antibodies response rate observed at 8 weeks. Patients were categorized on the basis of clinical symptoms into asymptomatic, mild, and moderate; 17.7% were asymptomatic, 60.5% showed mild symptoms, and 21.8% showed moderate symptoms of the disease. Males were seen to be more asymptomatic as compared with females (i.e., 59.1% to 40.9%). The serological test for SARS-CoV-2 has a high sensitivity at >2 weeks after the positive PCR result or onset of illness. In addition, the serological response differs among patients based on gender, age, as well as time between the onset of symptoms or PCR confirmation and sample collection for the study of antibody response.

Severity of COVID-19 reinfection and associated risk factors: findings of a cross-sectional study in Bangladesh

BackgroundCOVID-19 reinfected patients suffer from diverse health consequences. Information on the severity of COVID-19 reinfection is scarce. The current study aimed to determine the proportion of COVID-19 reinfection and risk factors associated with its severity. MethodsThis cross-sectional study targeted all COVID-19 patients reported in May 2021 at the Health Information Unit (HIU) of the Directorate General of Health Services (DGHS) of Bangladesh. We identified 473 (1.14%) reinfected patients out of 41408 diagnosed cases by reviewing their medical records. Considering the selection criteria and informed consent, we enrolled 404 reinfected patients. Data were collected through telephone interviews and reviewing medical records using a semi-structured questionnaire and a checklist. ResultsThe majority of the reinfected patients were urban residents (98.0%). Around 13.0% of reinfected patients had <90% oxygen saturation, and 64.0% had an interval of 3-6 months between two attacks. The severity of reinfection included asymptomatic (12.9%), mild (8.9%), moderate (66.3%), and severe (11.9%) forms of infection. An interval of 3-6 months between two attacks had less chance of having mild (AOR=0.031, {rho}=0.000), moderate (AOR=0.132, {rho}=0.017), and severe (AOR=0.059, {rho}=0.002) infections. Patients who maintained physical distance had less chance of moderate-intensity reinfection (AOR=0.137, {rho}=0.013), while the vaccinated patients had a higher chance of moderate (AOR=16.127, {rho}=0.001) and severe (AOR=3.894, {rho}=0.047) intensity reinfection. ConclusionTo avert COVID-19 reinfection and its severity, patients should be vigilant about preventive practices even after recovery. The study suggests vibrant interventions aligned with exposure, physical distancing, vaccination, and comorbidities for mitigating reinfection.

Methoprene treatment increases activity, starvation and desiccation risk of Queensland fruit fly.

Juvenile hormone is an important regulator of sexual development in insects, and application of methoprene, a juvenile hormone analogue, together with access to a protein-rich diet, has been found to accelerate sexual maturation of several tephritid fruit fly species including Queensland fruit fly Bactrocera tryoni ('Q-fly'). Such accelerated development is a potentially valuable means to increase participation of released males in sterile insect technique programs. However, there is a risk that benefits of accelerated maturation might be countered by increased vulnerability to starvation and desiccation. The present study investigates this possibility. After emergence, flies were treated with three levels of methoprene (0, 0.05%, and 0.5%) incorporated into a diet of sugar and yeast hydrolysate for two days after emergence. Survival of groups and individual flies was assessed under conditions of food stress, food and water stress, and ad libitum access to diet, and survival of individual flies was also assessed under desiccation stress. Most flies provided ad libitum access to diet were still alive at 7 days, whereas all stressed flies died within 4 days. Desiccation stressed flies had the shortest survival followed by food and water stress, and then food stress. Methoprene supplements increased susceptibility of flies to each stress. Flies subjected to food and water stress had the least lipid reserves at death, whereas flies subjected to desiccation stress retained the least water reserves. To investigate mechanisms that might underlie reduced survival under stress; we also quantified activity level of flies that were subjected to food and water stress and desiccation stress. Activity level was greater for flies provided methoprene, but did not vary with stress type or sex, suggesting that increased vulnerability of flies to stress is related to elevated metabolism associated with elevated activity. Deleterious effects of methoprene supplements on stress tolerance indicate a need for careful consideration of the conditions that will be encountered by flies in the field before deploying methoprene as a pre-release treatment in Q-fly sterile insect technique programs.

Differences in Clinical Nature and Outcome Among Young Patients Suffering from an Acute Coronary Syndrome.

PURPOSE: Acute coronary syndrome (ACS) is a life-threatening cardiac disease identified by acute, regional reductions in coronary blood flow, resulting in myocardial ischemia, or infarction, and manifesting as discomfort in the chest area, neck, or arms. Frequently, ACS is provoked by an atherosclerotic plaque; therefore, coronary atherosclerosis is converted into a chronic disease to an acute medical emergency. The purpose of this study was to explore the differences among these variables in patients less than 45 years of age suffering from this major health problem compared to older adults admitted with an ACS diagnosis, and to adopt an optimized temporary management. PATIENTS AND METHODS: A retrospective chart review study was conducted on a total of 652 ACS patients admitted at King Fahad Hospital of the University (KFHU) between 2015 and 2020. The patients' medical records were utilized for obtaining demographic data, presenting symptoms, risk factors, and clinical outcomes. RESULTS: Overall, 652 patients were enrolled. Of these, 109 patients (16.7%) were under 45, with a mean age of 38 ± 7. Younger patients showed a higher rate of palpitation (23.9% versus. 13.6%; P = 0.019). A positive smoking history and a family history of CAD were seen more often in younger patients (42.2% vs 27.3%, P < 0.001; 22.9% vs 9.4%, P < 0.001, respectively). Older patients had greater renal impairment with higher creatinine (median = 1.10 mg/dl (range, 0.3-13.0) vs 1.0 (0.3-19.0; p = 0. 001), BUN (median = 16.0 (mange, 0.9-141.0) vs 12.0 (0.9-49.0); P < 0.001)). Younger patients had higher levels of LDL and total cholesterol (median 138c. 115; p < 0.001) and cholesterol (median 209 vs 178.5; p < 0.001). Hospital mortality was 0.9% in younger patients versus 7.4% in older patients (P = 0.004). CONCLUSION: Palpitations, smoking, family history, higher LDL levels, and total cholesterol levels were more prevalent in adults younger than 45 years old with ACS. Impaired renal function, hypertension, and diabetes were more in older patients with ACS.

Toll-Like Receptor (TLR) Signaling Enables Cyclic GMP-AMP Synthase (cGAS) Sensing of HIV-1 Infection in Macrophages.

HIV-1 replicates in cells that express a wide array of innate immune sensors and may do so simultaneously with other pathogens. How a coexisting innate immune stimulus influences the outcome of HIV-1 sensing, however, remains poorly understood. Here, we demonstrate that the activation of a second signaling pathway enables a cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) response to HIV-1 infection. We used RNA sequencing to determine that HIV-1 alone induced few or no signs of an IFN-I response in THP-1 cells. In contrast, when supplemented with suboptimal levels of bacterial lipopolysaccharide (LPS), HIV-1 infection triggered the production of elevated levels of IFN-I and significant upregulation of interferon-stimulated genes. LPS-mediated enhancement of IFN-I production upon HIV-1 infection, which was observed in primary macrophages, was lost by blocking reverse transcription and with a hyperstable capsid, pointing to viral DNA being an essential immunostimulatory molecule. LPS also synergistically enhanced IFN-I production by cyclic GMP-AMP (cGAMP), a second messenger of cGAS. These observations suggest that the DNA sensor cGAS is responsible for a type I IFN response to HIV-1 in concert with LPS receptor Toll-like receptor 4 (TLR4). Small amounts of a TLR2 agonist also cooperate with HIV-1 to induce type I IFN production. These results demonstrate how subtle immunomodulatory activity renders HIV-1 capable of eliciting an IFN-I response through positive cross talk between cGAS and TLR sensing pathways. IMPORTANCE Innate immune activation is a hallmark of HIV-1 pathogenesis. Thus, it is critical to understand how HIV-1 infection elicits innate immune responses. In this work, we show that HIV-1 infection of macrophages leads to a robust type I interferon (IFN) production only when a second signaling event is initiated by a coexisting immunostimulatory molecule. Our results show that HIV-1 infection alone is not sufficient for triggering a strong IFN response. We find that bacterial membrane components, which are recognized by endosomal innate sensors, enable production of elevated levels of IFNs and significant upregulation of interferon-stimulated genes upon HIV-1 infection. This IFN response is dependent on viral DNA synthesis and prevented by a stable capsid, pointing to an essential role for a DNA sensing molecule. These observations provide new insights into how different innate immune recognition pathways synergize during HIV-1 infection and determine the outcome of innate responses.

Factors Influencing Participation in COVID-19 Clinical Trials: A Multi-National Study.

In 2020, the World Health Organization has characterized COVID-19, a disease caused by infection with the SARS-CoV-2 virus, as a pandemic. Although a few vaccines and drugs have been approved to, respectively, prevent or treat the disease, several clinical trials are still ongoing to test new vaccines or drugs to mitigate the burden of the pandemic. Few studies have shown the role of host genetics in disease prognosis and drug response highlighting the importance of diverse participation in COVID-19 clinical trials. The goal of this study is to assess public attitudes in Egypt, Saudi Arabia, and Jordan toward participating in COVID-19 clinical trials and to identify the factors that may influence their attitude. An online questionnaire was developed and distributed among the target group through social media platforms. The number of responses was 1,576. Three quarters (74.9%) of participants heard about clinical trials before, 57.6% of them had a positive attitude toward participation in COVID-19 clinical trials. The conduct of clinical trials in accordance with the scientific, research, and ethical guidelines was a strong predictor of willingness to participate in clinical trials. Other positive factors also included protection of family from COVID-19 and contributing to the return to normal community life as well as receiving additional healthcare benefit was the fourth significant predictor. On the other hand, the thought that clinical trials can have a negative impact on the health of participants strongly predicted the unwillingness of individuals to participate in such trials. This was followed by having limited information about the novel coronavirus and COVID-19 and the lack of trust in physicians and hospitals. In general, Arab citizens are accepting the concept and have a positive attitude toward COVID-19 clinical trials. Increasing awareness of COVID-19 and clinical trials, enforcing the concept of altruism, and placing clear policies in conducting clinical trials are needed to increase participation in clinical trials among Arabs.

Low-Temperature As-Grown Crystalline ß-Ga2O3 Films via Plasma-Enhanced Atomic Layer Deposition.

We report on the low-temperature growth of crystalline Ga2O3 films on Si, sapphire, and glass substrates using plasma-enhanced atomic layer deposition (PEALD) featuring a hollow-cathode plasma source. Films were deposited by using triethylgallium (TEG) and Ar/O2 plasma as metal precursor and oxygen co-reactant, respectively. Growth experiments have been performed within 150-240 °C substrate temperature and 30-300 W radio-frequency (rf) plasma power ranges. Additionally, each unit AB-type ALD cycle was followed by an in situ Ar plasma annealing treatment, which consisted of an extra (50-300 W) Ar plasma exposure for 20 s ending just before the next TEG pulse. The growth per cycle (GPC) of the films without Ar plasma annealing step ranged between 0.69 and 1.31 Å/cycle, and as-grown refractive indices were between 1.67 and 1.75 within the scanned plasma power range. X-ray diffraction (XRD) measurements showed that Ga2O3 films grown without in situ Ar plasma annealing exhibited amorphous character irrespective of substrate temperature and rf power values. With the incorporation of the in situ Ar plasma annealing process, the GPC of Ga2O3 films ranged between 0.76 and 1.03 Å/cycle along with higher refractive index values of 1.75-1.79. The increased refractive index (1.79) and slightly reduced GPC (1.03 Å/cycle) at 250 W plasma annealing indicated possible densification and crystallization of the films. Indeed, X-ray measurements confirmed that in situ plasma annealed films grow in a monoclinic ß-Ga2O3 crystal phase. The film crystallinity and density further enhance (from 5.11 to 5.60 g/cm3) by increasing the rf power value used during in situ Ar plasma annealing process. X-ray photoelectron spectroscopy (XPS) measurement of the ß-Ga2O3 sample grown under optimal in situ plasma annealing power (250 W) revealed near-ideal film stoichiometry (O/Ga of ∼1.44) with relatively low carbon content (∼5 at. %), whereas 50 W rf power treated film was highly non-stoichiometric (O/Ga of ∼2.31) with considerably elevated carbon content. Our results demonstrate the effectiveness of in situ Ar plasma annealing process to transform amorphous wide bandgap oxide semiconductors into crystalline films without needing high-temperature post-deposition annealing treatment.

Exendin-4 Attenuates Remodeling in the Remote Myocardium of Rats After an Acute Myocardial Infarction by Activating ß-Arrestin-2, Protein Phosphatase 2A, and Glycogen Synthase Kinase-3 and Inhibiting ß-Catenin.

PURPOSE: This study tested if the protective anti-remodeling effect of GLP-1 agonist Exendin-4 after an acute myocardial infarction (MI) in rats involves inhibition of the Wnt1/ß-catenin signaling pathway. METHODS: Rats were divided into sham, sham + Exendin-4 (10 µg/day, i.p), MI, and MI + Exendin-4. MI was introduced to rats by permanent left anterior descending coronary artery (LAD) ligation. RESULTS: On day 7 post-infraction, MI rats showed LV dysfunction with higher serum levels of cardiac markers. Their remote myocardia showed increased mRNA and protein levels of collagen I/III with higher levels of reactive oxygen species (ROS) and inflammatory cytokines, as well as protein levels of Wnt1, phospho-Akt, transforming growth factor (TGF-ß1), Smad, phospho-Smad3, α-SMA, caspase-3, and Bax. They also showed higher protein levels of phospho-glycogen synthase kinase-3ß (p-GSK3ß), as well as total, phosphorylated, and nuclear ß-catenin with a concomitant decrease in the levels of cyclic adenosine monophosphate (cAMP), mRNA of manganese superoxide dismutase (MnSOD), and protein levels of Bcl-2, ß-arrestin-2, and protein phosphatase-2 (PP2A). Administration of Exendin-4 to MI rats reduced the infarct size and reversed the aforementioned signaling molecules without altering protein levels of TGF-1ß and Wnt1 or Akt activation. Interestingly, Exendin-4 increased mRNA levels of MnSOD, protein levels of ß-arrestin-2 and PP2A, and ß-catenin phosphorylation but reduced the phosphorylation of GSK3ß and Smad3, and total ß-catenin levels in the LV of control rats. CONCLUSION: Exendin-4 inhibits the remodeling in the remote myocardium of rats following acute MI by attenuating ß-catenin activation and activating ß-arrestin-2, PP2A, and GSK3ß. Graphical Abstract A graphical abstract that illustrates the mechanisms by which Exendin-4 inhibits cardiac remodeling in remote myocardium of left ventricle MI-induced rats. Mechanisms are assumed to occur in the cardiomyocytes and/or other resident cells such as fibroblast. Β-catenin activation and nuclear translocation are associated with increased synthesis of inflammatory cytokines and transforming growth factor ß-1 (TGF-ß1). GSK3ß is inhibited by phosphorylation at Ser9. Under normal conditions, ß-catenin is degraded in the cytoplasm by the active GSK3ß-dependent degradation complex (un-phosphorylated) which usually phosphorylates ß-catenin at Ser33/37/Thr41. After MI, TGF-ß1, and Wnt 1 levels are significantly increased, the overproduction of Wnt1 induces ß-catenin stabilization and nuclear translocation through increasing the phosphorylation of disheveled (DVL) protein which in turn phosphorylates and inhibits GSK3ß. TGF-ß1 stimulates the phosphorylation of Smad-3 and subsequent nuclear translocation to activate the transcription of collage 1/III and α-smooth muscle actin (α-SMA). Besides, TGF-ß1 stabilizes cytoplasmic ß-catenin levels indirectly by phosphorylation of Akt at Thr308-induced inhibition of GSK3ß by increasing phosphorylation of Ser9. Exendin-4, and possibly through G protein-coupled receptors (GPCRs), increases levels of cAMP and upregulates ß-arrestin-2 levels. Both can result in a positive inotropic effect. Besides, ß-arrestin-2 can stimulate PP2A to dephosphorylation Smad3 (inhibition) and GSK3ß (activation), thus reduces fibrosis and prevents the activation of ß-catenin and collagen deposition.

Helicobacter pylori Eradication in Parkinson's Disease: A Randomized Placebo-Controlled Trial.

BACKGROUND: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD). OBJECTIVE: We aimed to evaluate the effects of HP eradication on PD symptoms. METHODS: In this parallel-group, double-blind, randomized placebo-controlled, single-center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS], timed tests, and home-based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality-of-life (Parkinson's Disease Questionnaire-39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline-to-week 12 change in ON medication MDS-UPDRS motor scores. Lactulose-hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test. RESULTS: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full-analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS-UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: -0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality-of-life outcome at weeks 12 and 52. Both the full-analysis and per-protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results. CONCLUSIONS: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society.

RNase L Amplifies Interferon Signaling by Inducing Protein Kinase R-Mediated Antiviral Stress Granules.

Virus infection leads to activation of the interferon (IFN)-induced endoribonuclease RNase L, which results in degradation of viral and cellular RNAs. Both cellular and viral RNA cleavage products of RNase L bind pattern recognition receptors (PRRs), like retinoic acid-inducible I (Rig-I) and melanoma differentiation-associated protein 5 (MDA5), to further amplify IFN production and antiviral response. Although much is known about the mechanics of ligand binding and PRR activation, how cells coordinate RNA sensing with signaling response and interferon production remains unclear. We show that RNA cleavage products of RNase L activity induce the formation of antiviral stress granules (avSGs) by regulating activation of double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) and recruit the antiviral proteins Rig-I, PKR, OAS, and RNase L to avSGs. Biochemical analysis of purified avSGs showed interaction of a key stress granule protein, G3BP1, with only PKR and Rig-I and not with OAS or RNase L. AvSG assembly during RNase L activation is required for IRF3-mediated IFN production, but not IFN signaling or proinflammatory cytokine induction. Consequently, cells lacking avSG formation or RNase L signaling produced less IFN and showed higher susceptibility during Sendai virus infection, demonstrating the importance of avSGs in RNase L-mediated host defense. We propose a role during viral infection for RNase L-cleaved RNAs in inducing avSGs containing antiviral proteins to provide a platform for efficient interaction of RNA ligands with pattern recognition receptors to enhance IFN production to mount an effective antiviral response.IMPORTANCE Double-stranded RNAs produced during viral infections serve as pathogen-associated molecular patterns (PAMPs) and bind pattern recognition receptors to stimulate IFN production. RNase L is an IFN-regulated endoribonuclease that is activated in virus-infected cells and cleaves single-stranded viral and cellular RNAs. The RNase L-cleaved dsRNAs signal to Rig-like helicases to amplify IFN production. This study identifies a novel role of antiviral stress granules induced by RNase L as an antiviral signaling hub to coordinate the RNA ligands with cognate receptors to mount an effective host response during viral infections.