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Anti-Glutamic Acid Decarboxylase Auto Antibody associated neurological disorder in pa...
Alisa Vasileva
Marcela Popescu

Alisa Vasileva

and 1 more

January 31, 2024
Objective: To report two cases with anti-GAD antibodies associated neurological disorder in patients with acute leukemia who received standard chemotherapeutic protocols. Clinical presentation and intervention: Case 1: patient with biphenotypic acute leukemia developed motor neurological symptoms while receiving induction therapy. Anti-GAD antibodies were demonstrable in the CSF and serum, and the patient responded to Intravenous Immunoglobulin (IVIG) therapy. Case 2: Patient with relapsed B-Acute lymphoblastic leukemia (ALL) after allogenic stem cell transplant developed progressive neurological symptoms. Anti-GAD65 antibodies were demonstrable in the serum, but not the CSF. The patient did not respond to IVIG and had to be given plasmapheresis and steroids. 2-year follow-up status of both patients is provided. Conclusion: Immunological etiology with Anti-GAD antibodies needs to be considered in the differential diagnosis of central and peripheral neurological illness in acute leukemia patients on standard chemotherapeutic protocol. IVIG is an effective treatment for this condition. However, in case of inadequate or no response, plasmapheresis with steroid or rituximab should be considered. Long-term management is required to prevent and manage relapse of autoimmune neurological illness.
Electro-osmotic Flow through Nanochannel with Different Surface Charge Configurations...
Abhijit Gogoi
Katha Reddy

Abhijit Gogoi

and 2 more

January 31, 2024
In the present study it is observed that alternate patterning of charged and neutral stripes on the surface of the graphene nanochannel lowers the water permeance and electro-osmotic flow velocity. However, for any charge configurations water permeance and electro-osmotic velocity through the nanochannel increase as surface charge density (σ) increases from 0.005 Cm^−2 to 0.025 Cm^−2 . With the further increase in σ, water permeance and electro-osmotic velocity through the nanochannel gradually decrease. Here factors like number of counter ions near the surface of the nanochannel, specific interactions between the wall and the water molecule/ion species play significant role in determining the flow behavior. These factors also influence the slip velocity of water molecules near the surface.
Silver nanoparticle interaction with ergosterol induces cell death and inhibits Trich...
Gowri Meiyazhagan
Muthu Devaraj

Gowri Meiyazhagan

and 5 more

January 31, 2024
In the present study, we have synthesized silver nanoparticles using Azadirachta indica (A. indica) skin extract as a reducing agent and characterized it. The antifungal activity of the silver nanoparticles was assessed against three different clinical isolates of T. asahii. The silver nanoparticles showed an efficient antifungal activity against T. asahii and, it was again established by time kill assay and Post-AntiFungal Effect (PAFE). Synergistic effect of silver nanoparticles with fluconazole or nystatin revealed a Minimum Inhibitory Concentration (MIC) decrease by 4-fold for both drugs studied and inhibited biofilm formation. An in vivo antifungal efficacy of silver nanoparticles using female Balb/C mice model revealed a mean 4log reduction of CFU in kidney when treated with 90mg/kg. Morphology changes of T. asahii cells, treated with silver nanoparticles, were observed using SEM. Cell membrane damage was quantified from the treated cells using flow cytometry by a Propidium Iodide (PI) uptake assay. The mechanism of action of the new silver nanoparticles against T. asahii was interpreted, and we learnt that they directly bind to ergosterol. Further, silver nanoparticles were not cytotoxic to normal cells (NIH 3T3) and hemocompatible. We concluded that the new silver nanoparticles exhibited promising antifungal activity against T. asahii.
Superior mediastinal syndrome in a child with B-cell acute lymphoblastic leukemia: A...
Rahat Ul Ain
Mahwish Faizan

Rahat Ul Ain

and 3 more

January 31, 2024
Superior mediastinal syndrome secondary to an anterior mediastinal mass can be seen in acute lymphoblastic leukemia of T-cell lineage. We report a 3 years old child with B-cell ALL, who presented with superior mediastinal syndrome. The CT scan chest showed a huge anterior mediastinal mass and the peripheral blood immunophenotying showed B-cell acute lymphoblastic leukemia. High-risk remission induction chemotherapy was given and he achieved remission by the end of induction therapy, both in terms of medullary and extramedullary disease. This is the first reported case of a pediatric B-cell ALL presenting with the superior mediastinal syndrome.
Assessing the climate change effects on climate variables and meteorological drought...
Fahimeh Mokhtari
Afshin Honarbakhsh

Fahimeh Mokhtari

and 4 more

January 31, 2024
Drought appears as an environmentally integral part of climate change. This study is designed to investigate the effect of climate change on meteorological drought in the Karkheh River Basin in near future (2071-2043), and distant future (2100-2072) periods. The outputs of GFDL-ESM2, HadGEM2-ES, IPSL-CM5A-LR, MIROC and NoerESM1-M models were downscaled under the RCP 2.6 and RCP8.5 scenarios using the Climate Change Toolkit (CCT) at 17 meteorological stations. To assess the uncertainty of the models and scenarios, the model outputs of the two future periods were compared with the base of the corresponding period using R2, RMSE, MAE indices. The best performing models were chosen for precipitation and maximum temperature, minimum temperature i.e. GFDL-ESM2, HadGEM2-ES and MIROC, respectively. An index, the standard precipitation-evapotranspiration index (SPEI) was also produced using the combination of all five models and under both scenarios. The climate change-induced changes were investigated by comparing the simulated data of the near and distant future periods with the statistics of the base period. The results showed that the basin annual precipitation will likely increase in both future periods, particularly in the near future. The annual maximum and minimum temperatures may also increase especially in the distant future. The rise in the maximum temperature will be possibly greater than the minimum temperature. Seasonal changes in maximum and minimum temperatures and precipitation indicate that the greatest increase in temperature and decrease in precipitation may occur in summer. Hence meteorological drought was also found to increase in the distant future.
Drug Therapy Problems and Health Related Quality of life among Chronic Diseases Patie...
Servet Gökşin
Abdikarim Mohamed Abdi

Servet Gökşin

and 3 more

January 31, 2024
ABSTRACT: Background: The burden of NCD continues to increase rapidly with lower resource areas affected the most. Aim is to evaluate status of care of NCD patients in a rural area of North Cyprus. Materials and Methods: A cross-sectional study involved patients with one or more NCD visiting a community pharmacy. Patient’s demographics, beliefs about medicine, lab values adherence and quality of life (QoL) were evaluated using validated tools. A clinical pharmacist assessed goals of therapy achievement, identified drug related problems (DRPs), and categorized DRPs using PCNE tool version 9.2. Results: Responders were 97 out of 200 eligible and approached. Median age was 62 (IQR=15) years and females formed 58.8%. Only 54% of hypertension patients reached target blood pressure. More than 40% of T2DM patients fail to achieve target HbA1c level. Most patients (71%) with Hypertension T2DM or CAD were not compliant in their lifestyle and diet and had a DRP (86.6%). Other than DRPs factors associated with lower QoL include female gender unemployment, and belief “that Medicines do more harm than good”. Conclusion: DRPs and non-adherence were prevalent while therapy targets were rarely achieved. Community pharmacist form an opportunity to improve outcomes in management of NCDs in rural areas. Keywords: healthcare; evidence-based medicine; public health; patient-centered care.
Scar cosmesis in major head and neck operations: a systematic review of skin closure...
Andrew Williamson
Andrew Connelly

Andrew Williamson

and 2 more

January 31, 2024
Background: The cosmetic appearance of head and neck surgical scars can have a major impact on body image and quality of life. Numerous wound closure methods such as staples, sutures, adhesives and surgical tape are available, and our aim is to investigate whether one closure method offers superior cosmetic outcomes over the others. Objectives: The primary outcome was patient and clinician reported cosmetic appearance. Secondary outcome measures such as post-operative complications were also measured. Design: A systematic review was undertaken of Pubmed, Web of Science and the Cochrane database. Searches were performed using the MeSH terms “tissue adhesives”, “wound closure techniques”, “surgical tape” and “sutures”, combined with various head and neck operations using Boolean operators. Results: The initial search found 2753 papers, of which 2,721 were excluded after removal of duplicates and screening. 32 papers underwent full text review and 7 were included in the review. The studies did not show any significant difference in cosmesis or wound complications. Surgical staples and tissue adhesives had significantly shorter wound closure time than sutures. No studies reported on head and neck scar’s impact on quality of life or body image. Conclusions: From the studies presented here, there is no significant difference in short term wound cosmesis using tissue adhesives, sutures, or surgical staples. However, the papers included are generally of poor quality and contained a moderate to high risk of bias, and thus further studies are needed to establish the cosmetic and quality of life impact of varying wound closure techniques following head and neck surgery.
A More Accurate Half-Discrete Hilbert-Type Inequality Involving One Higher-Order Deri...
Bing He
Bicheng Yang

Bing He

and 1 more

January 31, 2024
By means of the weight functions, Hermite-Hadamard's inequality and the technique of real analysis, a new more accurate half-discrete Hilbert-type inequality involving one higher-order derivative function is given. The equivalent conditions of the best possible constant factor related to a few parameters, the equivalent forms, several particular inequalities and the operator expressions are considered.
Is there any association between direction of nasal deviation and hand dominance in m...
Melekber Çavuş Özkan
Erdem Tezel

Melekber Çavuş Özkan

and 1 more

January 31, 2024
Objectives: This study aims to investigate incidence of nostril asymmetry and deviation of nasal bony pyramid and caudal septum and to examine their association with dominant hand in male adolescents. Methods: Totally 546 male healthy adolescents aged 15 to 17 years were included. Each participant was examined for presence or absence of nasal bone pyramidal deviation, caudal septal deviation, side of deviation, and nostril asymmetry. The dominant hand was recorded. Results: Of participants, 85 were aged 15 years, 291 were aged 16 years, and 168 were aged 17 years. Mean age was 16.148±0.667 years. Of all participants, 91% (n=497) were right-handed and 9% (n=49) were left-handed. Distribution of the dominant hand across age groups was comparable (p=0.921). In case of deviation to the right, 61.2% (n=74) were right-hand dominant, while 58.3% (n=7) of those with deviation to the left were left-hand dominant. According to hand dominance and size of nostrils, 92.1% (n=105) of those with a larger left nostril were right-handed and 7.9% (n=9) were left-handed. Conclusions: Male adolescents had a significant deviation of caudal septum to the right side with smaller right nostrils. However, hand dominance and side of deviation were not significantly associated with nasal bony pyramid and caudal septum.
A Scale Development: Brain Fog Scale
DERYA atik
Ayşe İnel Manav

DERYA atik

and 1 more

January 31, 2024
Background: This research was conducted to objectively evaluate the level of brain fog that may develop due to many reasons. Methods: This was a methodological study. This study was conducted between April and May 2021 in Turkey. Content validity ratio, Exploratory Factor Analysis, Confirmatory Factor Analysis, Kaiser-Meyer-Olkin analysis and Bartlett’s test of sphericity, Item analysis, Cronbach’s alpha coefficient, Spearman-Brown, Guttman Analysis and test-retest correlations validity-reliability analysis were performed. The statistical meaningfulness level in all tests was determined as p<0.05. Results: As a result of context validity, factor analysis and item analysis, a 30 item scale with 3 subscale was obtained. In the scale, the variance amount explained by the three sub components was on a very good level (77.43%). The fact that all of the Cronbach alpha, Spearman-Brown and Guttman internal consistency coefficients of the scale and all of its subscale are above 0.70. When the test retest reliability coefficients of the scale was examined, the scale was found to present consistent results in different applications and the scale was found to be reliable with regard to the constancy coefficient. Conclusion: The Brain Fog Scale consists of 30 items and three subscales. It is a valid and reliable instrument that is appropriate for Turkish society. It can be used to determine the level of brain fog in the last 30 days.
A comparison between GeneXpert testing and the Berlin-Charité diagnostic protocol for...
Eduardo Becerril Vargas
Andrea Delgado Cueva

Eduardo Becerril Vargas

and 16 more

January 31, 2024
Since the beginning of the SARS-CoV-2 pandemic healthcare professionals have found it necessary to generate diagnostic methods for the disease that are easy to use, reliable, and accessible. The Berlin-Charité protocol has been one of the most recommended methods for detecting SARS-CoV-2 from the onset of the pandemic. However, new diagnostic techniques such as GeneXpert have been developed and proven to be efficient, fast, and easy to use to detect infected patients. The purpose of this study, conducted at the National Institute for Respiratory Diseases in Mexico, was to compare the diagnostic performance of the Berlin-Charité protocol and GeneXpert for the detection of SARS-CoV-2, evaluating a cohort of 135 Mexican patients. For statistical analysis, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios for each assay were calculated. The diagnostic parameters for GeneXpert were found to be 100% in both sensitivity and specificity. The Berlin-Charité protocol performance had a sensitivity of 72% and specificity of 100%. With this study, it can be concluded that the diagnosis of SARS-Cov_2 infection through GeneXpert was 29% more specific than the Berlin protocol.
An update of COVID-19 pandemic in India
Kumudhaveni B
Thirumal  Margesan

Kumudhaveni B

and 2 more

January 31, 2024
China declared officially outbreak as an epidemic on January 20 after findings of human-to-human transmission. On March 11, 2020, World Health Organization (WHO) declared COVID-19 a global Pandemic after the spread and severity of the outbreak. The virus is transmitted from the infected person through respiratory droplets and by touching the surfaces, contaminated with viruses. At present, India is in the middle of the second wave due to a variant virus. Covid-19 cases have risen faster in the second wave than the first wave in India. Union Health Ministry of India issued the latest guidelines for the treatment of Covid-19 depends upon the severity of the disease i.e. mild, moderate and severe. Ministry of Ayush, Government of India has given guidelines for the treatment of Covid-19. Vaccines are a critical tool in the battle against the COVID-19 war. Covishield and Covaxin vaccines are being administered in India. Even if we are vaccinated, we have to take certain preventive measures until the COVID-19 cases dropdown.
Ascending aortic pseudoaneurysm: rare complication of aortic valve surgery
Mleyhi Sobhi
Khadhar Yaasine

Mleyhi Sobhi

and 7 more

January 31, 2024
Introduction : False aneurysm of the ascending aorta is a rare complication of aortic valve surgery. It can be associated with significant mortality. Caser report : We report the case of a false aneurysm of the ascending aorta, diagnosed 1 year after aortic valve replacement and a replacement of the ascending aorta by a supra coronary tube for an endocarditis in a patient already operated within the framework of tight aortic stenosis on bicuspidia with dilatation of the ascending aorta. The patient was reoperated with placement of extracorporeal circulation in femoro-femoral associated with selective cannulation of carotids. Peroperatively, we found a dehiscence between the proximal aorta and the Dacron tube that was closed by patches patched by the right trans-auricular approach in circulatory arrest. The bacteriological examination of the specimen was positive for negative Staphylococcus coagulase. The follow-up was simple with a total of 40 days of antibiotic therapy. Conclusion : The ascending aortic pseudoaneurysm is a rare or even exceptional complication of cardiac surgery, the etiology, pathophysiology and natural course of which are still poorly understood. This complication of cardiac surgery remains fraught with high mortality, despite advances in cardiovascular surgery. Each case of ascending aortic pseudoaneurysm is individual and should be managed accordingly. Key-words : Pseudoaneurysm ; valvular surgery; ascending aorta, infection
Surgical balloon catheter fenestration and thrombectomy for spontaneous coronary arte...
Adam Williams
Jatin Anand

Adam Williams

and 4 more

January 31, 2024
A 51-year-old female presented with left anterior descending spontaneous coronary artery dissection (SCAD). After initial treatment with conservative therapy, she developed recurrent chest pain and complete thrombosis of the LAD. Using a novel hybrid treatment, she was revascularized with balloon catheter thrombectomy and fenestration, followed by coronary artery bypass grafting.
Macrophages-derived, LRG1-enriched extracellular vesicles exacerbate aristolochic aci...
Wenjuan Jiang
Jiahui Dong

Wenjuan Jiang

and 6 more

January 31, 2024
Background and Purpose: Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some herbal medicines, but treatment remains ineffective. We previously found NADPH oxidases 4 (NOX4), which regulates oxidative stress, play an important role in kidney injury model. However, its regulatory mechanism of action in AAN is still obscure. Experimental Approach: In this study, we established AAN model in vivo, a co-culture system of macrophage and TEC, and macrophage/TEC conditioned media culture model in vitro respectively. Key Results: We found macrophages infiltration promoted injury,oxidative stress and apoptosis of TEC. Furthermore, the role of macrophage in AAN was dependent on macrophages-derived EV. Importantly, we found that macrophages-derived, Leucine-rich α-2-glycoprotein 1(LRG1)-enriched EV induced TEC injury and apoptosis of via a TGFβR1-dependent process. Mechanistically, macrophages-derived, LRG1-enriched EV mediating TECs injury by upregulating NOX4 in AAN model. Conclusion and Implications: We identified EV as a potential link between macrophage-mediated inflammation and AAI-induced TEC oxidative stress and apoptosis. This study may help design a better therapeutic strategy to treat AAN patients.
Increase of Low-Frequency Modes of User Dynamics in Online Social Networks During Ove...
Masaki Aida
Kouichi Nagatani

Masaki Aida

and 2 more

January 31, 2024
User dynamics in online social networks have a significant impact on not only the online community but also real-world activities. As examples, we can mention explosive user dynamics triggered by social polarization, echo chamber phenomena, fake news, etc. Explosive user dynamics are frequently called online flaming. The wave equation-based model for online social networks (called the oscillation model) is a theoretical model proposed to describe user dynamics in online social networks. This model can be used to understand the relationship between explosive user dynamics and the structure of social networks. However, since the oscillation model was introduced as a purely theoretical model of social networks, it is necessary to confirm whether the model describes real phenomena correctly or not. In this paper, we first show a prediction from the oscillation model; the low-frequency oscillation mode of user dynamics will be dominant when the structure of online social networks changes so that user activity is activated. To verify the predictions with actual data, we show spectral analyses of both the log data of posts on an electronic bulletin board site and the frequency data of word search from Google Trends. The results support the predictions from the theoretical model.
Prohys - A Novel Hysteric-Proteretic Switch
Azeemuddin Syed

Azeemuddin Syed

January 31, 2024
Hysteresis is a widely known and applied phenomenon whereas proteresis, it’s complimentary effect, has yet to be explored. A proteretic device is a bistable switch whose states depend on system’s future unlike hysteresis where the states depend on history. As a result, realization of this switch would be of great interest and may find vast applications. Therefore, the first contribution of this work is to model the proteretic phenomenon and implement in circuit theory. This model has been achieved by providing a constraint feedforward path to a hysteric feedback system and the circuit implementation was done using op-amps. As mentioned, the hysteresis and proteresis are two complementary phenomenon, hence, the second contribution of this work is to introduce “Prohys” a switch, the two corresponding states of which are hysteresis and proteresis. The switching between hysteresis and proteresis was achieved by varying the constraint feedforward path in proteretic device. It can also be achieved by adding a variable memory feedback system to the aforementioned device. We present the theoretical model, design, simulation and circuit implementation of the proposed switch using op-amps. The experimental results obtained from the circuit design match well with the theoretical models proposed.
Statistical and Spectral Analysis of Wind Power: Fractional Oscillation Dynamics
Abelito Filipe
Koichi Shimakawa

Abelito Filipe Belo

and 1 more

January 31, 2024
Time-dependent changes of the wind speed, as an example in Hera Campus (East Timor), are analyzed by the statistical and the autocorrelation function in time domain and by the frequency spectrum (frequency domain) using the Fast Fourier Transform (FFT). The wind speed can be modeled using the Weibull distribution function. The autocorrelation function in time domain shows roughly a non-exponential decay with periodicity. The power spectrum shows two peaks and nearly 1/f  nature at high frequencies, closing to the Kolmogorov prediction with  = 5/3. A Cole-Davidson type generalization of wind dynamics, originating from the fractional dynamics of oscillation, may be useful for analyzing wind power.
Validation of the new microarray platform ALEX for specific IgE detection of respirat...
Paola Quan
Marina Sabate-Bresco

Paola Quan

and 12 more

January 31, 2024
Background: As the use of multiplex specific IgE (sIgE) detection methods becomes increasingly widespread, proper comparative validation assessments of emerging new platforms are vital. The objective of this study was to assess the clinical and technical performance of the ALEX platform (MacroArray Diagnostics), in comparison to the ImmunoCAP ISAC 112 microarray and the ImmunoCAP singleplex method (ThermoFisher Scientific) in the diagnosis of pollen (cypress, grass, olive), dust mite Dermatophagoides pteronyssinus, Alternaria alternata, fruit (apple, peach) and nut (walnut, hazelnut and peanut) allergy. Methods: We enrolled 153 allergic patients and 16 non-atopic controls. sIgE assays were conducted using ISAC112, ALEX version 2 (ALEX2), and ImmunoCAP for whole extracts and major components. Technical validation of ALEX2 was performed by measuring repeatability and inter-assay, inter-batch and inter-lab reproducibility. Results: When measured globally (detection by one or more allergen components), ALEX2 showed adequate sensitivity and specificity for most of the allergens studied, comparable in general to that of ISAC112 (except for olive pollen and walnut) and similar to that of ImmunoCAP whole extract measurements. Component-by-component analysis showed comparable results for all techniques, except for Ole e 1 and Jug r 3 in both ISAC112 and ImmunoCAP comparisons, and Alt a 1, when compared with ISAC112. Continuous sIgE levels correlate with sIgE by ImmunoCAP. Good reproducibility and repeatability were observed for ALEX2. Conclusions: ALEX2 shows sound technical performance, and adequate diagnostic capacity, comparable in general to that of ISAC112 and ImmunoCAP for some aeroallergens and plant-food allergies in Mediterranean patients.
PREVALENCE, RISK FACTORS, PHARMACOEPIDEMIOLOGY AND INNOVATIONS PREVENTION OF BRONCHIA...
Bakhtiyor Ganiev

Bakhtiyor Ganiev

January 31, 2024
Background: Industrial chemical compounds are also included in the list of causative factors of bronchial asthma. The contribution of industrial allergens to the formation of bronchial asthma is undeniable. The paper considers the degree of knowledge of the prevalence and risk factors for the formation of bronchial asthma to give a reasonable assessment of domestic and foreign researchers’ published works to draw logical conclusions from the research done. It helps to predetermine more relevance of studying pharmacoepidemiology, measures prevention. Methods: A stratified random sample design was used in this study, including custom-designed questionnaires. Two sets of surveys were used to identify asthma-like symptoms, which were then validated by respiratory physicians using a pulmonary function test and bronchial dilation test. Results: In studies carried out in conjunction with professional pathologists, children were found to be sensitized to industrial allergens (nickel, chromium, formaldehyde, etc.), which contribute to the formation of bronchial asthma. Determining, however, is the presence of atopy. Conclusions: Today the prevalence of BA is a serious problem, not only from a medical but also from the social and economic point of view. Many primary prevention strategies did not show in randomized clinical trials sufficient proofs so that they were used in clinical practice. Preventive interventions need to be taken to reduce the disease burden at the community level. It will predetermine further relevance of studying pharmacoepidemiology and measures for primary secondary, and tertiary prevention of this disease.
Translocator protein ligand Ro5-4864 promotes melanogenesis in a TSPO independent man...
Yunyun Yue
Zi-xian Liao

Yunyun Yue

and 9 more

January 31, 2024
The 18-kDa translocator protein (TSPO) is highly conserved among different species but with perplexing biochemical function. Multiple ligands of TSPO show commendable regulatory activities among lots of biological functions, such as neuroinflammation, cholesterol transport and so on. These researches support that TSPO may be a potential target for disease treatment and drug development. Previous studies have shown that its ligand agonist benzodiazepines have the effect of promoting melanin, but the specific mechanism is still unclear. In this research, we firstly confirmed the melanogenesis promotion of Ro5-4864 in mouse melanoma cell line, human skin tissue and zebrafish embryos through inducing melanin synthesis and melanosome transport. Molecular genetics and pharmacological studies showed that TSPO deficiency did not affect melanin production in B16F10 cells and zebrafish embryos, nor did it affect melanin promotion effect of Ro5-4864. The expression of lots of melanogenesis related proteins, such as TYR, TRP-1, DCT, Mlph and Rab27 were upregulated in Ro5-4864 treatment cell with or without Tspo. These results indicated that Ro5-4864 induced melanogenesis in a TSPO independent manner. However, further research is still needed to clarify the direct downstream target of Ro5-4864 in promoting melanogenesis.
Impact of SARS-CoV-2 infection (COVID-19) on cytochromes P450 activity assessed by th...
Camille Lenoir
Jean Terrier

Camille Lenoir

and 8 more

January 31, 2024
Background and purpose Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 infection, is a severe acute respiratory syndrome with an underlying inflammatory state. We have previously demonstrated that acute inflammation modulates cytochromes P450 (CYP) activities in an isoform-specific manner. We therefore hypothesized that COVID-19 might also impact CYP activities, and thus aimed to evaluate the impact of acute inflammation in the context of SARS-CoV-2 infection on the six main human CYPs activity. Experimental Approach This prospective observational study was conducted in 28 patients hospitalized at the Geneva University Hospitals (Switzerland) with a diagnosis of moderate to severe COVID-19. They received the Geneva phenotyping cocktail orally during the first 72h of hospitalization and after three months. Capillary blood samples were collected 2h after cocktail administration to assess the metabolic ratios (MRs) of CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A. CRP, IL-6 and TNF-α levels were also measured in blood. Key Results CYP1A2, CYP2C19, and CYP3A MRs decreased by 52.6% (p=0.0001), 74.7% (p=0.0006) and 22.8% (p=0.045), respectively, in COVID-19 patients. CYP2B6 and CYP2C9 MRs increased by 101.1% (p=0.009) and 55.8% (p=0.0006) respectively. CYP2D6 MRs variation did not reach statistical significance (p=0.072). As expected, COVID-19 was a good acute inflammation model as mean serum levels of CRP, IL-6 and TNF-α were significantly (p<0.001) higher during SARS-CoV-2 infection. Conclusion and implications CYP activities are modulated in an isoform-specific manner by SARS-CoV-2 infection. The pharmacokinetics of CYP substrates, whether used to treat the disease or as the usual treatment of patients, could be therefore clinically impacted.
Developing an effective scale-down model for a suspension adapted HEK293T-derived len...
Hamza Patel
Peter Archibald

Hamza Patel

and 6 more

July 28, 2021
Lentiviral vectors (LVV) represent an important tool for vaccine development and other therapeutic modalities. However, inefficiencies in LVV manufacturing processes, such as the inability to achieve high cell densities with HEK293T cell lines in a fed batch process, have resulted in poor upstream yields. Optimisation of cell culture conditions is needed to improve upstream yields, which can be expedited by high-throughput screening (HTP). In this work, we describe the use of the 24 deep square well (24-DSW) microwell platform to develop a scale-down mimic of GSK’s established stable suspension LVV production process model at 2 L bioreactor scale. We found that matched mixing time was an effective basis for scale-translation between the stirred tank reactor (STR) and microwells. The growth kinetics and LVV productivity profile in the microwell were reproducible and comparable to the 2 L bioreactor process model. In both vessels, a 6-fold increase in cell density was achieved at the harvest time point and high cell viability (i.e. > 90 %) was also maintained throughout the entirety of the cultures. The 24-DSW model, therefore, is an effective scale-down model for larger-scale stirred-tank bioreactor culture and provides an important tool for rapid, high-throughput optimization of the LVV production process.
Mediators Linking Obesity to Childhood Asthma: the Role of Puberty, Physical Fitness,...
Yang-Ching Chen
Ming-Wei Su

Yang-Ching Chen

and 3 more

January 31, 2024
Background: Obesity and asthma are highly associated, but the mechanisms underlying the association remain unknown. We examined five mediators linking obesity with childhood asthma: (1) pulmonary function impairment, (2) airway inflammation, (3) physical fitness, (4) sleep-disordered breathing (SDB), and (5) early puberty. Methods: A Mendelian randomization (MR) study with mediation analysis of data obtained from 5,965 children as part of the Taiwan Children Health Study. Cross-sectional regression analysis, MR two-stage least squares method, and MR sensitivity analysis were carried out to investigate each causal pathway. Prospective cohort analyses were used to confirm the findings. Results: The increased asthma risk associated with obesity was found to be mostly mediated through impaired pulmonary function, low physical fitness, early puberty. In the MR analysis, body mass index was negatively associated with FEV1/FVC and physical fitness index (β= −2.17 and −0.71; 95% CI, −3.92 to −0.42 and −1.30 to −0.13, respectively) and positively associated with early puberty (OR, 1.09; 95% CI, 1.02–1.17). High FEV1/FVC and physical fitness index reduced the risk of asthma (OR, 0.98 and 0.93; 95% CI, 0.97–0.99 and 0.88–0.98, respectively), whereas SDB and early puberty increased the risk of asthma (OR, 1.03 and 1.22; 95% CI, 1.01–1.05 and 1.05–1.42, respectively). The three main mediators were low physical fitness, impaired pulmonary function, and early puberty, with mediation proportions of 91.4%, 61.6%, and 28.3%, respectively. Temporal causality was further strengthened in prospective cohort analyses. Conclusions: Interventions promoting physical fitness and pulmonary function might effectively reduce obesity-induced asthma risk.
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