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The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. Novel SARS-CoV-2 lineages P.1 and P.2, first identified respectively in Manaus and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed a whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraiba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) aiming to identify SARS-CoV-2 mutations that could be involved in the surge of COVID19 cases in Brazil. Here, we showed a widespread dispersion of P.1 and P.2 across Brazilian regions. Except for Manaus, P.2 was the predominant lineage identified country-wise. P.2 lineage was estimated to have originated in February, 2020 and has diverged into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December. P.1 origin was inferred to have happened in August 2020. We also confirmed the presence of the variant under investigation (VUI) NP13L recently described in the southernmost region of Brazil to have spread across the Northeastern states. P.1, P.2 and NP13L are descended from the ancient B.1.1.28 strain, although during the first phase of the pandemic in Brazil presence of B.1.1.33 strain was also reported. Here, for the first time, we investigate the possible occurrence of a new variant of concern descending from B.1.1.33 that also carries the E484K mutation. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to early identify novel variants of concern and to monitor for vaccine effectiveness.
Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil
As the Italian health system is regionally based, COVID-19 emergency actions are based on a general lockdown imposed by national authority and then management at local level by 21 regional authorities. Therefore, the pandemic response plan developed by each region led to different approaches. The aim of this paper is to analyze whether differences in patient management may have influenced the local course of the epidemic. The analysis on the 21 Italian regions considers the strategies adopted in terms of hospitalization, treatment in the ICU and at home. Moreover, an in-depth analysis was carried out on: Lombardia, which adopted a hospitalization approach; Veneto, which tended to confine patients at home; and Emilia Romagna, which adopted a mixed hospitalization-home based approach. The majority of regions implemented a home-based approach, while the hospital approach was followed in three regions (Lombardia, Piemonte, and Lazio), mainly limited to the first period of the outbreak. All regions in the later phases tended to reduce hospitalization, preferring to confine patients at home. This comparison, highlighting the different phases of the pandemic, outlined that the adoption of home-based practices contributed to limiting infection rates among patients and health professionals as well as decreasing the number of deaths.
Analysis of the Different Approaches Adopted in the Italian Regions to Care for Patients Affected by COVID-19
A record outbreak of community-spread COVID-19 started on 10 May 2021, in Taiwan. In response to the COVID-19 pandemic, care facilities have adopted various protocols using instant communication technology (ICT) to provide remote yet timely healthcare while ensuring staff safety. The challenges of patient evaluation in the emergency department (ED) using ICT are seldom discussed in the literature. The objective of this study was to investigate the factors influencing the utility of ICT for patient assessment in emergency settings during the pandemic. The patient flow protocol and the ED layout were modified and regionalized into different areas according to the patients risk of COVID-19 infection. Nine iPads were stationed in different zones to aid in virtual patient assessment and communication between medical personnel. A focus group study was performed to assess and analyze the utility of the ICT module in the ED. Eight emergency physicians participated in the study. Of them, four (50%) had been directly involved in the development of the ICT module in the study hospital. Three main themes that influenced the application of the ICT module were identified: setting, hardware, and software. The setting theme included six factors: patient evaluation, subspecialty consultation, patient privacy and comfortableness, sanitation, cost, and patient acceptability. The hardware theme included six factors: internet connection, power, quality of image and voice, public or personal mode, portable or fixed mode, and maintenance. The software theme included six factors: platform choices, security, ICT accounts, interview modes, video/voice recording, and time limitation. Future studies should focus on quantifying module feasibility, user satisfaction, and protocol adjustment for different settings.
Challenges of Using Instant Communication Technology in the Emergency Department during the COVID-19 Pandemic: A Focus Group Study
LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01C8.56 mol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2(D); a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2(D). Circulating 8 and M2(D), having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2(D). This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.
Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule
Nonprofit organizations operating in civil society have become the main channel for social service provision in most neoliberal welfare economies. Social service nonprofits (SSNs) deliver essential services mainly to vulnerable and marginalized populations. Since the outbreak of COVID-19, SSNs have been at the frontline of dealing with its socioeconomic consequences. This paper focuses on the activities and responses to the crisis of SSNs in Israel. Interviews with SSN directors (N = 17) show that they dealt with growing demands for services due to the social implications of the pandemic, along with operational difficulties, such as deterioration in clients condition, disruption in service continuity, and reduced funding and staff. Next to these difficulties, the findings highlighted the social innovations adopted by SSNs to maintain service provision, such as implementing remote service technologies, forming collaborations, and recruiting volunteers. Implications for the social services and policies are presented and discussed. [ FROM AUTHOR] Copyright of Human Service Organizations: Management, Leadership & Governance is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
From Crisis to Opportunity: Israeli Social Service Nonprofits Responses to COVID-19
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare peripheral cytotoxic T-cell lymphoma, clinically resembling panniculitis. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune overactivation, triggered by underlying conditions. SPTCL presenting with HLH may represent a severe and rapidly progressive disease course. Currently, there is no standardized approach to treatment of HLH secondary to underlying SPTCL. A 34-year-old Asian male presented with a several months history of high fevers, weight loss, and nonpruritic purple discoloration of the skin. He had a skin biopsy showing atypical lymphohistiocytic panniculitis with dermal mucinosis and erythrophagocytosis consistent with SPTCL. The patient was initiated on treatment with dexamethasone and cyclosporine A. Almost immediate improvement of his skin lesions was noted and laboratory abnormalities trended toward baseline within 2 weeks. He noted complete symptom resolution after 3 months on therapy. SPTCL may be treated effectively with cyclosporine A and steroids to achieve rapid clinical and symptom management of this rare malignancy.
Hemophagocytic Lymphohistiocytosis as the Initial Presentation of Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Rare Case Responding to Cyclosporine A and Steroids
COVID-19 induced restrictions resulted in a lowered fine aerosol particle and trace gas concentration across several urban places around the world, providing a natural opportunity to study effects of anthropogenic activities on emissions of air pollutants. Impact of sudden suspension of human activities on air pollution was analyzed by studying the change in satellite retrieved NO 2 concentrations and top-down NOx emission over the urban and rural areas around Delhi. NO 2 was chosen for being the most indicative of emission intensity due to its short lifetime of the order of a few hours in the planetary boundary layer. We present a robust temporal comparison of Ozone Monitoring Instrument (OMI) retrieved NO 2 column density during the lockdown with the counterfactual baseline concentrations, extrapolated from the long-term trend and seasonal cycle components of NO 2 using observations during 2015 to 2019. NO 2 columns in the urban area of Delhi experienced an anomalous relative change ranging from 60.0% decline during the Phase 1 of lockdown (March 25-April 13, 2020) to 3.4% during the post-lockdown Phase 5. In contrast, we find no substantial reduction in NO 2 concentrations over the rural areas. To clarify the quantitative impact of the lockdown measures, weekly top-down NOx emissions were estimated from TROPOspheric Monitoring Instrument (TROPOMI) retrieved NO 2 by accounting for horizontal advection derived from the steady state continuity equation. NOx emissions from urban areas and power plants exhibited a mean decline of 72.19% and 53.4% respectively in Phase 1 compared to the pre-lockdown business-as-usual phase. Due to absence of confounding emission source activity during lockdown, emission estimates over urban areas and power-plants were validated with respective electricity generation reports and Googles mobility reports. A higher anomaly in emission estimates suggests that comparison of only concentration change, without accounting for the dynamical and photochemical conditions, may mislead evaluation of lockdown impact. Our results are also useful for optimizing bottom-up emission inventories.
Nitrogen Oxides Concentration and Emission Change Detection During COVID-19 Restrictions in North India
Background The time-concentrated nature of the first wave of the COVID-19 epidemic in England in March and April 2020 provides a natural experiment to measure changes in antibody positivity at the population level before onset of the second wave and initiation of the vaccination programme. Methods Three cross-sectional national surveys with non-overlapping random samples of the population in England undertaken between late June and September 2020 (REACT-2 study). 365,104 adults completed questionnaires and self-administered lateral flow immunoassay (LFIA) tests for IgG against SARS-CoV-2. Findings Overall, 17,576 people had detectable antibodies, a prevalence of 4.9% (95% confidence intervals 4.9, 5.0) when adjusted for test characteristics and weighted to the adult population of England. The prevalence declined from 6.0% (5.8, 6.1), to 4.8% (4.7, 5.0) and 4.4% (4.3, 4.5), over the three rounds of the study a difference of -26.5% (-29.0, -23.8). The highest prevalence and smallest overall decline in positivity was in the youngest age group (18-24 years) at -14.9% (-21.6, -8.1), and lowest prevalence and largest decline in the oldest group (>74 years) at -39.0% (-50.8, -27.2). The decline from June to September 2020 was largest in those who did not report a history of COVID-19 at -64.0% (-75.6, -52.3), compared to -22.3% (-27.0, -17.7) in those with SARS-CoV-2 infection confirmed on PCR. Interpretation A large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first wave. Widespread vaccination is needed to confer immunity and control the epidemic at population level. Funding This work was funded by the Department of Health and Social Care in England.
Prevalence of antibody positivity to SARS-CoV-2 following the first peak of infection in England: Serial cross-sectional studies of 365,000 adults
In this study, we examined various forms of mathematical models that are relevant for the containment, risk analysis, and features of COVID-19. Greater emphasis was laid on the extension of the Susceptible-Infectious-Recovered (SIR) models for policy relevance in the time of COVID-19. These mathematical models play a significant role in the understanding of COVID-19 transmission mechanisms, structures, and features. Considering that the disease has spread sporadically around the world, causing large scale socioeconomic disruption unwitnessed in contemporary ages since World War II, researchers, stakeholders, government, and the society at large are actively engaged in finding ways to reduce the rate of infection until a cure or vaccination procedure is established. We advanced argument for the various forms of the mathematical model of epidemics and highlighted their relevance in the containment of COVID-19 at the present time. Mathematical models address the need for understanding the transmission dynamics and other significant factors of the disease that would aid policymakers to make accurate decisions and reduce the rate of transmission of the disease.
Mathematical modeling for infectious viral disease: The COVID-19 perspective
Currently, there is a paucity of clinical trial designs that comprehensively evaluate the efficacy of most complementary and alternative systems of medicine (CAMs) like Ayurveda. Several factors such as complex interventions, individualized therapy, etc., make designing Ayurveda clinical trials challenging. The prevalent randomized control trial (RCT) designs largely involve symptomatology/pathology-based recruitment and standardized interventions in carefully monitored trial environments. The present paper critically reviews the suitability of the dominant RCT model to Ayurveda and argues for newer, more sensitive trial models including modified RCTs and other clinical trial designs. It also explores the merits of a non-hierarchical approach to clinical evidence generation.
RCTs and other clinical trial designs in Ayurveda: A review of challenges and opportunities
Serological assays are important tools to identify previous exposure to SARS-CoV-2, helping to track COVID-19 cases and determine the level of humoral response to SARS-CoV-2 infections and/or immunization to future vaccines. Here, the SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to homogeneity and high yield using a single chromatography step. The purified SARS-CoV-2 nucleocapsid protein was used to develop an indirect enzyme-linked immunosorbent assay for the identification of human SARS-CoV-2 seroconverts. The assay sensitivity and specificity were determined analyzing sera from 140 RT-qPCR-confirmed COVID-19 cases and 210 pre-pandemic controls. The assay operated with 90% sensitivity and 98% specificity; identical accuracies were obtained in head-to-head comparison with a commercial ELISA kit. Antigen-coated plates were stable for up to 3 months at 4 C. The ELISA method described is ready for mass production and will be an additional tool to track COVID-19 cases.
Antigen production and development of an indirect ELISA based on the nucleocapsid protein to detect human SARS-CoV-2 seroconversion
COVID-19 vaccines are being rapidly developed and human trials are under way. Almost all of these vaccines have been designed to induce antibodies targeting the spike protein of SARS-CoV-2 in expectation of neutralizing activities. However, nonneutralizing antibodies are at risk of causing antibody-dependent enhancement. Further, the longevity of SARS-CoV-2-specific antibodies is very short. Therefore, in addition to antibody-inducing vaccines, novel vaccines developed on the basis of SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs) should be considered. Here, we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the nonstructural polyprotein 1a of SARS-CoV-2. Eighty-two peptides were first predicted as epitope candidates based on bioinformatics. Fifty-four of the 82 peptides showed high or medium binding affinities to HLA-A*02:01. HLA-A*02:01 transgenic mice were then immunized with each of the 54 peptides encapsulated into liposomes. The intracellular cytokine staining assay revealed that 18 out of 54 peptides were active as CTL epitopes because of the induction of gamma interferon (IFN-)-producing CD8(+) T cells. Of the 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant CTL epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant over the other peptides. Surprisingly, all mice immunized with the liposomal 10-peptide mixture did not show the same reaction pattern to the 10 peptides. There were three response patterns, suggesting the existence of an immunodominance hierarchy following peptide vaccination, which may provide more variations in the epitope selection for designing CTL-based COVID-19 vaccines. IMPORTANCE For the development of vaccines based on SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs), we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the nonstructural polyprotein 1a of SARS-CoV-2. Out of 82 peptides predicted by bioinformatics, 54 peptides showed good binding affinities to HLA-A*02:01. Using HLA-A*02:01 transgenic mice, 18 in 54 peptides were found to be CTL epitopes in the intracellular cytokine staining assay. Out of 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant. Surprisingly, all immunized mice did not show the same reaction pattern to the 10 peptides. There were three reaction patterns, suggesting the existence of an immunodominance hierarchy following peptide vaccination, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines.
Identification of HLA-A*02:01-Restricted Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 That May Be Natural Targets of CD8(+) T Cell Recognition In Vivo
INTRODUCTION: The neurological impact (or lack thereof) of certain medical histories and imaging findings is important to understand in the context of air and spaceflight. There are a number of neurological conditions that, if present in pilots and astronauts, carry variable (and sometimes adverse) functional implications for safety and overall mission success. In this systematic overview, the authors will refer to the relevant clinical and radiological features of brain tumors and vascular anomalies, cerebral edema and intracranial hypertension, concussion and the traumatic brain injury (TBI) spectrum, hematomas, cerebrospinal fluid circulation anomalies including hydrocephalus and sequestrations, spinal degenerative changes, and cerebral ischemia and demyelination. It is notable that these last two conditions have recently been reported to be a complication in some people with coronavirus disease 2019 (COVID-19). A paradigm for practical neurological workup of symptomatic pilots and astronauts will be discussed, as will the controversial notion of pre-emptive radiological screening (vs. not screening) in asymptomatic or clinically occult situations. The concepts of medical surveillance in the setting of known or diagnosed pathologies, and expert panel review and simulator and flight checks in complex neurological cases, are also elaborated on in this paper. We believe this overview will contribute toward the enhancement of a broad understanding of neurological conditions, their clinical workup, and their precautionary management in the setting of aviation and aerospace.Khurana VG, Jithoo R, Barnett M. Aerospace implications of key neurological conditions. Aerosp Med Hum Perform. 2021; 92(2):113119.
Aerospace Implications of Key Neurological Conditions
Vaccines are among the most successful and cost-effective public health tools and have greatly contributed to eliminating or controlling several serious vaccine-treatable diseases over the past century. To curb the spread of COVID-19, efficacious vaccination is emerging as essential in mitigating the disease and preventing deaths. Health care workers (HCW) are one of the first groups to receive vaccinations, so it is important to consider their attitudes to COVID-19 vaccination to better address barriers to widespread vaccination acceptance. This study aimed to evaluate variables that are linked with the recommendation of vaccines and intention to take-up vaccination against COVID-19 among the HCWs, in the context of the current pandemic. The study was conducted during the first week of the vaccination campaign dedicated to Italian HCWs, beginning in December 2020, and it involved all doctors in a public hospital in Sicily. The following questionnaires were administered: (1) The perceived vaccine trust questionnaire, measuring the degree of trust in vaccines by healthcare professionals both in general and for the protection of healthcare professionals themselves and patients;(2) the positive and negative affect scale-state (PANAS), for assessing positive and negative emotions in relation to their work as frontline care providers;(3) The locus of control of behaviour (LCB) to measure the extent to which subjects perceive responsibility for their personal behaviour (internal vs. external);(4) recommendation vaccines item, referring to the intention to recommend vaccination. The findings suggest that socio-demographic control variables (age, gender, and seniority) showed little or no predictive power in vaccine recommendation, while vaccine confidence, positive emotions, and internal locus of control were excellent predictors of vaccine recommendations by doctors. Younger doctors, both in age and experience, are more confident in vaccines and recommend them more frequently. It is essential to improve institutional communication addressed to doctors to enhance their role as vaccination facilitators.
What Prompts Doctors to Recommend COVID-19 Vaccines: Is It a Question of Positive Emotion?
Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by a newly identified coronavirus called the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) which was initially emerged in Wuhan, China in late December 2019 and then rapidly extended to other countries worldwide. COVID-19 is now known as a pandemic threat to global public health. It possesses a wide spectrum of clinical manifestations, ranging from asymptomatic infection to mild, moderate, and ultimately severe pneumonia accompanied by multi-organ system dysfunction that can cause the death of the afflicted patients. The host immune system plays a critical role in defending against potentially pathogenic microorganisms such as coronaviruses, and it eliminates and eradicates these invading agents by triggering effective immune responses. However, there exists evidence indicating that in critically ill cases of the COVID-19, dysregulated immune responses and hyper-inflammation lead to acute respiratory distress syndrome (ARDS) and multi-organ failure. Achieving a profound understanding of the pathological immune responses involved in the pathogenesis of COVID-19 will boost our comprehending of disease pathogenesis and its progression toward severe form, contributing to the identification and rational design of effective therapies. In this review, we have tried to summarize the current knowledge regarding the role of immune responses against SARS-CoV-2 and also give a glimpse of the immune evasion strategies of this virus.
A review on the immune responses against novel emerging coronavirus (SARS-CoV-2)
The article turns its attention to the informally and diffusely educational profile of the pandemic experience and the practices activated for its management Particular attention is paid to the models of care implicitly conveyed and connected to the family dimension, in the multiplication of the conciliation needs determined by the confinement The aim is to illuminate the contents and teaching of a social education that risks contributing problematically to the aggravation of a gender imbalance
Donne e Covid-19. L'educazione sociale di una fatica indicibile
The COVID-19 outbreak has ravaged all societal domains, including education. Home confinement, school closures, and distance learning impacted students, teachers, and parents lives worldwide. In this study, we aimed to examine the impact of COVID-19-related restrictions on Italian and Portuguese students academic motivation as well as investigate the possible buffering role of extracurricular activities. Following a retrospective pretestCposttest design, 567 parents (n(Italy) = 173, n(Portugal) = 394) reported on their childrens academic motivation and participation in extracurricular activities (grades 1 to 9). We used a multi-group latent change score model to compare Italian and Portuguese students: (1) pre-COVID mean motivation scores; (2) rate of change in motivation; (3) individual variation in the rate of change in motivation; and (4) dependence of the rate of change on initial motivation scores. Estimates of latent change score models showed a decrease in students motivation both in Italy and in Portugal, although more pronounced in Italian students. Results also indicated that the decrease in students participation in extracurricular activities was associated with changes in academic motivation (i.e., students with a lower decrease in participation in extracurricular activities had also a lower decrease in motivation). Furthermore, students age was significantly associated with changes in motivation (i.e., older students had lower decrease). No significant associations were found for students gender nor for parents education. This study provides an important contribution to the study of students academic motivation during home confinement, school closures, and distance learning as restrictive measures adopted to contain a worldwide health emergency. We contend that teachers need to adopt motivation-enhancing practices as means to prevent the decline in academic motivation during exceptional situations.
Parents Perceptions of Student Academic Motivation During the COVID-19 Lockdown: A Cross-Country Comparison
Objective: To explore potential causal genetic variants and genes underlying the pathogenesis of uterine leiomyomas (ULs). Methods: We conducted the summary data-based Mendelian randomization (SMR) analysis and performed functional mapping and annotation using FUMA to examine genetic variants and genes that are potentially involved in the pathogenies of ULs. Both analyses used summarized data of a recent genome-wide association study (GWAS) on ULs, which has a total sample size of 244,324 (20,406 cases and 223,918 controls). For the SMR analysis, we performed separate analysis using CAGE and GTEx eQTL data. Results: Using the CAGE eQTL data, our SMR analysis identified 13 probes tagging 10 unique genes that were pleiotropically/potentially causally associated with ULs, with the top three probes being ILMN_1675156 (tagging CDC42, PSMR=8.03E-9), ILMN_1705330 (tagging CDC42, PSMR=1.02E-7) and ILMN_2343048 (tagging ABCB9, PSMR=9.37E-7). Using GTEx eQTL data, our SMR analysis did not identify any significant genes after correction for multiple testing. FUMA analysis identified 106 independent SNPs, 24 genomic loci and 137 genes that are potentially involved in the pathogenesis of ULs, seven of which were also identified by the SMR analysis. Conclusions: We identified many genetic variants, genes, and genomic loci that are potentially involved in the pathogenesis of ULs. More studies are needed to explore the exact underlying mechanisms in the etiology of ULs.
Exploring potential causal genes for uterine leiomyomas: A summary data-based Mendelian randomization and FUMA analysis
Objective: Use of real-time continuous glucose monitoring (rtCGM) has been shown to improve glycemic control in patients with type 2 diabetes (T2D) who are treated with intensive insulin therapy. However, most T2D patients are denied coverage for rtCGM due to failure to meet payer eligibility requirements: treatment with 3 insulin injections (or pump) and history of 4 /day blood glucose testing. We investigated the relevance of these criteria to successful rtCGM use. Methods: This 6-month, prospective, interventional, single-arm study assessed the clinical effects of use rtCGM in patients with T2D treated with basal insulin only or noninsulin therapy. Primary outcomes were changes in HbA1c, average glucose, glycemic variability (% coefficient of variation), and percent of time in range (%TIR), below range (%TBR) and above range (%TAR). Results: Thirty-eight patients were included in the analysis (10.1% 1.8% HbA1c, 54.7 10.2 years, 35.6 6.4 body mass index). At 6 months, we observed reductions in HbA1c (?3.0% 1.3%, P < 0.001) and average glucose (?23.6 38.8, P < 0.001). %TIR increased 15.2 22.3, from 57.0 29.9 to 72.2 23.6, P < 0.001, with all patients maintaining %TBR targets (<4% at 70 mg/dL, <1% at <54 mg/dL). No changes in glycemic variability were observed. The greatest improvements in %TIR and %TAR were seen in patients treated with 1 medication. Conclusions: rtCGM use was associated with significant glycemic improvements in T2D patients treated with basal insulin only or noninsulin therapy. Given the growing body of evidence supporting rtCGM use in this population, insurance eligibility criteria should be modified to expand rtCGM use by T2D patients treated with less intensive therapies.
Use of Real-Time Continuous Glucose Monitoring Improves Glycemic Control and Other Clinical Outcomes in Type 2 Diabetes Patients Treated with Less Intensive Therapy
The species Chiliadenus glutinosus (L.) Fourr. has a large number of therapeutic uses reported in the traditional Spanish medicine. The growing interest in preserving the ethnopharmacological knowledge related to the botanical diversity existing in Spain and the interest in achieving scientific validation of the therapeutic properties of medicinal species has led to the development of this study. To do it, all the known medicinal uses of Ch. glutinosus in Spain were compiled, then an exhaustive bibliographic research on its chemical composition was carried out, and finally, an in silico validation of the bioactive phytochemicals present in a higher proportion in the essential oil of Ch. glutinosus: camphor, borneol, lucinone, glutinone, quercetin, kutdtriol, and kaempferol; in an attempt to justify the reported traditional uses of the species. It was found that much of the traditional medicinal uses of Ch. glutinosus, along with the biological activity of its phytochemicals, are supported by scientific evidence. The results place this species in a prominent position to initiate possible lines of research to develop new, more effective drugs and improve therapies to treat conditions and diseases that affect the different organic systems of the human being.
Ethnobotanical Research and Compilation of the Medicinal Uses in Spain and the Active Principles of Chiliadenus glutinosus (L.) Fourr. for the Scientific Validation of Its Therapeutic Properties