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On April 13, 2021, U.S. authorities announced an investigation into potential adverse events associated with the Johnson & Johnson (Janssen, J&J) COVID-19 vaccine and recommended “a pause in the use of this vaccine out of an abundance of caution.” We examined whether public attitudes toward COVID-19 vaccination shifted after this recommended suspension using an interrupted time series with data from the Census Bureau’s Household Pulse Survey, which was fielded bi-weekly between January 6 and April 26, 2021. We found no significant changes in trends of the proportion of the U.S. adult population hesitant about getting a COVID-19 vaccine, but a significant increase in concerns about safety and efficacy of COVID-19 vaccines among the already hesitant population.

Recently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79-85%) 14-90 days after vaccination to 53% (43-62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.

Objective To combat the wide-spread transmission of COVID-19, many countries, including the United Kingdom, have imposed nationwide lockdowns. Little is known about how these public health safety measures affect pregnant mothers and their offspring. This study aimed to explore the impact of COVID-19 public health safety measures on births in Scotland. Study Design Cross-sectional study. Methods Using routinely collected health data on pregnancy and birth in Scotland, this study compares all births (N = 7342) between 24th of March and May 2020 to births in the same period in 2018 (N = 8323) to investigate the potential negative impact of public health safety measures introduced in Scotland in spring 2020. Birth outcomes were compared using Mann-Whitney-U tests and chi-square tests. Results Mothers giving birth during the pandemic tended to combine breastfeeding and formula-feeding rather than exclusively breastfeed or exclusively formula-feed, stayed in hospital for fewer days and more often had an epidural or a spinal anaesthetic compared to women giving birth in 2018. Conclusion Overall, results suggest little impact of public health safety measures on birth outcomes. Further research is needed to explore the longer-term impacts of being born in the pandemic on both maternal mental health and child development.

Objectives Among the few studies examining patterns of COVID-19 spread in border regions, findings are highly varied and partially contradictory. This study presents empirical results on the spatial and temporal dynamics of incidence in 10 European border regions. We identify geographical differences in incidence between border regions and inland regions, and we provide a heuristic to characterise spill-over effects. Study Design Observational spatiotemporal analysis. Methods Using 14-day incidence rates (03/2020 to 05/2021) for border regions around Germany, we delineate three pandemic ‘waves’ by the dates with lowest recorded rates between peak incidence. We mapped COVID-19 incidence data at the finest spatial scale available and compared border regions’ incidence rates and trends to their nationwide values. The observed spatial and temporal patterns are then compared to the time and duration of border controls in the study area. Results We observed both symmetry and asymmetry of incidence rates within border pairs, varying by country. Several asymmetrical border pairs feature temporal convergence, which is a plausible indicator for ‘spill-over’ dynamics. We thus derived a border incidence typology to characterise (1) symmetric border pairs, (2) asymmetric border pairs without spill-over effects, and (3) asymmetric with spill-over effects. In all groups, border control measures were enacted, but appear to have been effective only in certain cases. Conclusions The heuristic of border pairs provides a useful typology for highlighting combinations of spill-over effects and border controls. We conclude that border control measures may be effective if the timing and the combination with other non-pharmaceutical measures is appropriate.

Quantitation of mHLA-DR and nCD64 is useful in understanding the dysregulated host response. The down regulation of HLA-DR expression on the circulating monocytes (mHLA-DR) is associated with anti-inflammatory response, and an increased expression of CD64 on neutrophil surface (nCD64) is associated with pro-inflammatory response. Quantitation of these antigen expression using beads (QuantiBRITE™ PE) is a precision technique. These beads are reported to be stable for 24 h after reconstitution. We report the results of our investigation examining the stability of QuantiBRITE PE beads over a period of 4-week post-reconstitution. The data suggest that reconstituted QuantiBRITE PE beads, if stored in dark at 2-8 °C, can be effectively used for up to 2 weeks for determining nCD64 and mHLA-DR antibody bound per cell (ABC) values.

Grain size is subtly regulated by multiple signaling pathways in rice. Alternative splicing is a general mechanism that regulates gene expression at the post-transcriptional level. However, to our knowledge, the molecular mechanism underlying grain size regulation by alternative splicing is largely unknown. GS3, the first identified QTL for grain size in rice, is regulated at the transcriptional and post-translational level. In this study, we identified that GS3 is subject to alternative splicing. GS3.1 and GS3.2, two dominant isoforms, accounts for about 50% and 40% of total transcripts, respectively. GS3.1 encodes the full-length protein, while GS3.2 generated a truncated proteins only containing OSR domain due to a 14 bp intronic sequence retention. Genetic analysis revealed that GS3.1 overexpressors decreased grain size, but GS3.2 showed no significant effect on grain size. Furthermore, we demonstrated that GS3.2 disrupts GS3.1 signaling by competitive occupation of RGB1. Therefore, we draw a conclusion that the alternative splicing of GS3 decreases the amount of GS3.1 and GS3.2 disrupts the GS3.1 signaling to inhibit the negative effects of GS3.1 to fine-tune grain size. Moreover, the mechanism is conserved in cereals rather than in Cruciferae, which is associated with its effects on grain size. The results provide a novel, conserved and important mechanism underlying grain size regulation at the post-transcriptional level in cereals.

Rheumatic heart disease (RHD) is a completely preventable, life-threatening complication of group A streptococcal pharyngitis and the commonest cause of acquired heart disease in children and young adults in low- and middle-income countries. Conventional control measures are faced with many obstacles including the difficulty of early diagnosis of bacterial pharyngitis and acute rheumatic fever (ARF) leading to late presentation with established RHD which is not curable. Recent evidence confirmed the role of echocardiography screening of asymptomatic children in the early detection of ‘latent' RHD. Benzathine penicillin prophylaxis was shown to be effective in halting the progression of latent RHD. There is enough evidence to warrant the implementation of control strategies that use lower thresholds for the diagnosis of group A streptococcal infection and ARF and we believe that it is high time to introduce an echocardiography screen-to-treat policy in endemic areas.

Of the 971 patients admitted to our Clinic with suspected COVID-19, 15 (1.5%) presented with two consecutive attacks of diarrhea. One of those patients (a 47-year-old woman) required admission to the intensive care unit and mechanical ventilation. She died on the 11th day of hospitalization (18th day of illness). The first attack of diarrhea in those patients occurred on the 6th (4th-7th) day of disease and lasted 3 (3-5) days. The second attack of diarrhea developed 11 (8-12) days after the initial onset of diarrhea. Despite the existing trend, the difference in the duration of the diarrhea and the maximum number of bowel movements per day between the first and second attacks was not statistically significant (p = 0.130; p = 0.328). There was no significant difference between the patients with a double attack of diarrhea and those with no diarrhea, regarding the results of the complete blood count, biochemical blood tests, and inflammation biomarkers. Resumen: De los 971 pacientes admitidos en nuestra clínica por sospecha de COVID-19, 15 (1.5%) presentaron dos ataques de diarrea consecutivos. Uno de dichos pacientes (una mujer de 47 años) requirió admisión a la unidad de cuidados intensivos y ventilación mecánica. Murió el 11.o día de hospitalización (18 días de enfermedad). El primer ataque de diarrea en dichos pacientes ocurrió el 6.o (4.o-7.o) día de enfermedad, con una duración de 3 (3-5) días. El segundo ataque de diarrea se desarrolló 11 (8-12) días después del comienzo inicial de diarrea. A pesar de la tendencia existente, la diferencia en la duración de la diarrea y el número máximo de movimientos intestinales por día entre el primer y el segundo ataque no fue estadísticamente significativa (p = 0.130; p = 0.328). Tampoco existió diferencia significativa respecto a los resultados del conteo sanguíneo completo, las pruebas bioquímicas sanguíneas, ni los biomarcadores inflamatorios, entre los pacientes que presentaron un doble ataque de diarrea y los que no presentaron diarrea.

We retrieved data on 8,940 anaphylaxis cases post-COVID-19 vaccination from the US Vaccine Adverse Event Reporting System and the European EudraVigilance from week 52/2020 through week 31/2021 and compared them with those of other vaccines. Overall, 837,830,000 COVID-19 vaccine doses were delivered in the US and Europe during the study period, for which the vaccine name was known. The mean anaphylaxis rate was estimated at 10.67 cases per 106 doses of COVID-19 vaccines (range: 7.99-19.39 cases per 106 doses depending on the vaccine). COVID-19 vaccines ranked fifth in reported anaphylaxis rates, behind rabies, tick-borne encephalitis, measles-mumps-rubella-varicella, and human papillomavirus vaccines (70.77, 20, 19.8, and 13.65 cases per 106 vaccine doses, respectively). COVID-19 vaccines are within the range of anaphylaxis rates reported across several common vaccines in these two passive reporting systems. These data should be communicated to reassure the general population about the safety profile of COVID-19 vaccines.

In functional arterial studies using wire myography, the determination of a vessel’s standardized normalization factor (factor k) is an essential step to ensure optimal contraction and relaxation by the arteries when stimulated with their respective vasoactive agents and to obtain reproducible results. The optimal factor k for several arteries have been determined, however, the optimal initial tension and factor k for the arteries involved in erection remains unknown. Hence, in the present study we set out to determine the optimal factor k for the internal iliac artery, proximal and distal internal pudendal artery (IPA), and dorsal penile artery. After isolating, harvesting, and mounting the arteries from male Sprague-Dawley rats on a multi wire myograph, we tested arterial responsivity to high K+-stimulation when the factor k was set at 0.7, 0.8, 0.85, 0.9, 0.95, 1.0, 1.1, and 1.2 to determine the factor k setting that results in the greatest K+-induced active force production for each vessel type. The data showed the optimal factor k is 0.90-0.95 for the dorsal penile, distal internal pudendal and internal iliac arteries while it is 0.85-0.90 for proximal internal pudendal artery. These optimal values corresponded to initial passive tension settings of 1.10±0.16 - 1.46±0.23, 1.28±0.20 - 1.69±0.34, 1.03±0.27 - 1.33±0.31, and 1.33±0.31 - 1.77±0.43 mN/mm for the dorsal penile, distal IP, proximal IP, and internal iliac arteries, respectively.

To prepare various root active promoters for expressing transgenes and prevent gene silencing caused by the repeated use of the same promoter, the expression characteristics of various root active promoters were comparatively evaluated using GUS as a reporter gene. The high-affinity potassium transporter (HKT1;1), the Shaker family potassium ion channel (SKOR), the Shaker family inward rectifying potassium channel (AKT1), the major facilitator superfamily protein (MFS1), and the senescence associated gene 14 (SAG14) promoter from Arabidopsis (Arabidopsis thaliana) were used, and for comparison, four additional constitutive or green tissue specific promoters in the expression vectors were also employed. As the Gateway cloning technology provided by Invitrogen can offer high efficiency and cloning reliability, and easy manipulation of fusion constructs in vitro, our expression vectors are based on binary (destination) vectors compatible with this cloning technique. These destination vectors are also advantageous for stable expression of the transgene, as the heat shock protein terminator is utilized. The AtHKT1;1, SKOR, AKT1, MFS1 and SAG14 promoters were all active in roots but showed slightly different tissue specificities: AtHKT1;1, SKOR, and MFS1 were dominantly active in vascular bundle tissue, while AtHKT1;1 and MFS1— but not SKOR, AKT1, and SAG14—were active in root tips. SKOR showed the strongest root-specificity, and SAG14 showed the highest activity among the five root active promoters. The activity of MFS was developmentally regulated. These destination vectors are now available to express multiple transgenes in transgenic plants, especially in roots.

Objective We investigated whether it is possible to induce a state of “LPS-sensitization” in neurons of primary cultures from rat dorsal root ganglia by pre-treatment with ultra-low doses of LPS. Methods DRG primary cultures were pre-treated with low to ultra-low doses of LPS (0.001–0.1 µg/ml) for 18 h, followed by a short-term stimulation with a higher LPS-dose (10 µg/ml for 2 h). TNF-α in the supernatants was measured as a sensitive read out. Using the fura-2 340/380 nm ratio imaging technique, we further investigated the capsaicin-evoked Ca2+-signals in neurons from DRG, which were pre-treated with a wide range of LPS-doses. Results Release of TNF-α evoked by stimulation with 10 µg/ml LPS into the supernatant was not significantly modified by pre-exposure to low to ultra-low LPS-doses. Capsaicin-evoked Ca2+-signals were significantly enhanced by pre-treatment with LPS doses being above a certain threshold. Conclusion Ultra-low doses of LPS, which per se do not evoke a detectable inflammatory response, are not sufficient to sensitize neurons (Ca2+-responses) and glial elements (TNF-α-responses) of the primary afferent somatosensory system.

Widespread vaccination in pursuit of herd immunity has been recognized as the most promising approach to ending the global pandemic of coronavirus disease 19 (COVID-19). The vaccination of children and adolescents has been extensively debated and the first COVID-19 vaccine is now approved in European countries for children aged > 12 years of age. Our study investigates vaccination hesitancy in a cohort of German secondary school students. We assessed 903 students between age 9 and 20 in the period between 17 May 2021 and 30 June 2021. 68.3% (n = 617) reported intention to undergo COVID-19 vaccination, while 7% (n = 62) did not want to receive the vaccine and 15% (n = 135) were not yet certain. Age and parental level of education influenced COVID-19 vaccine hesitancy. Children under the age of 16 as well as students whose parents had lower education levels showed significantly higher vaccine hesitancy. Conclusion: Identifying subsets with higher vaccination hesitancy is important for targeting public information campaigns in support of immunization. What is Known:• The willingness to receive COVID-19 vaccination among adults in Europe is about 70%, but data for children and adolescents is lacking.• The lack of immunization in younger cohorts represents a significant barrier to achieving herd immunity, and also leaves children and adolescents vulnerable to acute and long-term morbidity from natural COVID-19 infections. What is New:• Intention-to-vaccinate among children and adolescents is high (~ 70%); conversely, vaccination hesitancy is low.• Age and parental level of education influenced COVID-19 vaccine hesitancy among children and adolescents.

There is a dearth of research in Latin America regarding risk and protective factors affecting older adults’ cognition. This study aimed to investigate the factors mediating the association between occupational complexity and late-life cognition and daily function in a sample of Hispanic older adults. Participants (n = 588) aged 65 years and older underwent clinical, functional, and cognitive assessments. Mediation analyses revealed that depressive symptoms mediated the relationship between occupational complexity and cognitive as well as functional outcomes. Results provide evidence that depression may act as a risk factor for worse outcomes, even if older adults had a cognitively demanding occupation.

Increasing evidence points to host genetics as a factor in COVID-19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5-Δ32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-Δ32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-Δ32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-Δ32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.

Background: To explore how sexual activity was impacted by coronavirus disease 2019 (COVID-19) lockdown measures in the general adult population. Methods: A cross-sectional survey was conducted among 6,003 Italian adults aged 18–74 years who were representative of the Italian general population. Study subjects were recruited at the time of the nationwide stay-at-home order (from April 27 to May 3, 2020). We identified characteristics associated with decreased frequency of sex during lockdown, differentiating between cohabiting and non-cohabiting subjects. Results: Over one-third (35.3%) of Italians reported to have changed their sexual activity during lockdown (8.4% increased and 26.9% decreased). When focusing on cohabitants (N = 3,949, 65.8%), decreased sexual activity (20.7%) was more frequently reported by men (22.3%; compared to women, multivariable odds ratio 1.23; 95% confidence interval, 1.05–1.44), younger subjects (P for trend

Objectives In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27. Study design Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021. Methods A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval. Results Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12–18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31–June 6 (excess deaths: 1431–2587; excess percentage: 5.95–10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures. Conclusions For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.

Aims Recent large randomized controlled trials (RCTs) have demonstrated efficacy of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in both preventing and treating heart failure (HF). SGLT2i‐induced reversal of left ventricular remodelling has been proposed as a mechanism contributing to this effect. Methods and results We performed a systematic review and meta‐analysis of RCTs to compare SGLT2i versus placebo (treatment duration >3 months) on cardiac remodelling parameters as measured by cardiac magnetic resonance imaging (cMRI) in patients with HF and/or diabetes. The PubMed and ClinicalTrials.gov databases were searched until 15 June 2021. Our primary outcome was change in absolute left ventricular mass (LVM) from baseline to study endpoint. Secondary outcomes included changes in LVM indexed to body surface area, left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) from baseline to study endpoint. The Cochrane Collaboration's tool was used to assess risk of bias. Five studies representing 408 patients were included. SGLT2i was associated with greater LVM regression compared to placebo (MD, −5.76 g; 95% CI, −10.87 g to −0.64 g, I 2 = 73%; overall effect, P

Objective To describe the clinical characteristics and outcomes of pediatric COVID-19 in Thailand, where favipiravir is the mainstay of antiviral treatment. Methods We conducted a hospital based observational cohort study of COVID-19 among children. The study included children (age

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with very limited treatment options. Stem cells have been raised as a new treatment modality for these patients. We have designed a single-center, prospective, open-label, and single arm clinical trial to assess the safety, feasibility, and rather efficacy of administrating allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) in ALS patients. We enrolled 17 patients with confirmed ALS diagnosis with ALS Functional Rating Scale-Revised (ALSFRS-R) (

Suppression of cellular O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) can repress proliferation and migration of various cancer cells, which opens a new avenue for cancer therapy. Based on the regulation of insulin gene transcription, we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells. The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)), an internal reference (red fluorescent protein), and an operator (neuronal differentiation 1), which serves as a “sweet switch” to control GFP expression in response to cellular O-GlcNAcylation changes. The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines. Using the fluorescent reporter, we screened 120 natural products and obtained one compound, sesamin, which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro. Altogether, the present study demonstrated the development of a novel strategy for anti-tumor drug screening, as well as for conducting gene transcription studies., Graphical abstract Image 1, Highlights • The reporter developed in this study is living cell-based with convenient utility. • The method can be used for high-throughput screening. • The reporter is versatile with potential applicability in the discovery of OGT/GFAT inhibitors and antitumor drugs.

Aims Evaluate whether UK National Institute for Health & Care Excellence (NICE) chronic heart failure (HF) guidelines can be safely and effectively refined through specialist referral management. Methods and results All referrals to a UK centre 1/3/2019–30/5/2019 and 1/6/2020–31/7/2020 were reviewed by HF specialists. Patients were triaged to specialist assessment in HF clinic, according to the NICE HF diagnostic pathway [urgency based on N‐terminal pro brain natriuretic peptide (NTproBNP) levels], or the referrer given remote Advice & Guidance (A&G), to aid primary care management. Standardized triage criteria for recommending primary care management were (i) presentation inconsistent with HF, (ii) competing comorbidity/frailty meant specialist assessment in clinic not in patient's best interests, (iii) recent assessment for same condition, or (iv) patient had known HF. Following triage patients managed in the primary care were categorized as low or high risk of adverse outcomes. Outcome measures were 90 day all‐cause and HF hospital admission and mortality rates. Four hundred and eighty‐six patients had the median age of 80 (74–86) years, and 253 (52%) were male. Two hundred and six (42%) had NTproBNP > 2000 pg/mL. Primary care management was recommended for 128 patients (26%): 105 (22%) A&G alone and 23 input from community HF nurse specialists. Primary care management was recommended due to the following: presentation inconsistent with HF 53 (42%), more important competing comorbidity/frailty 35 (27%), recent assessment 17 (13%), and known HF 23 (18%). Patients managed in primary care had higher rates of all‐cause hospitalization (30% vs. 19%; P = 0.018) and death (7% vs. 2%; P = 0.0054) than those seen in HF clinic. Of those managed in primary care, 50 (39%) were determined to be at low risk and 78 (61%) at high risk. High‐risk patients were older (87 vs. 80 years; P = 0.0026), had much higher NTproBNP (2666 vs. 697 pg/mL; P

Aims Cardiac involvement is crucial factor determining outcomes of light chain (AL) amyloidosis. This study evaluated whether capillary density (CD) quantified from endomyocardial biopsy is associated with structural and functional parameters of amyloid heart. Also, we investigated whether capillary density improves the prognostic value of the current staging system in AL amyloidosis patients with cardiac involvement. Methods and results A total of 67 patients with biopsy‐proven AL cardiac amyloidosis were prospectively enrolled in this study. All patients underwent transthoracic echocardiography and EBM at the time of diagnosis. Left ventricle global longitudinal strain was evaluated on two‐dimensional strain echocardiography. The primary endpoint was all‐cause mortality. Amyloid load and capillary density were calculated on endomyocardial biopsy stained immunohistochemically with antibody against amyloid P and CD31, respectively. Among the study population, 37 patients (55.2%) were classified as Stage IV, and the cumulative incidence of death at 1 year was 34% (23 patients). A total of 65 (97%) patients underwent chemotherapy. CD showed a significant correlation with left ventricle global longitudinal strain (r = 0.274, P = 0.025), log N‐terminal pro‐B type natriuretic peptide (r = −0.311, P = 0.005), and amyloid load (r = −0.438, P 220/mm2 (P = 0.026 by log‐rank test). A model based on the 2012 Mayo staging system and CD showed significantly better discrimination and reclassification ability than a model using the 2012 Mayo staging system alone (C‐index 0.582 vs.0.689, P for difference

OBJECTIVES: SARS-CoV-2 exhibits tropism for the gastrointestinal tract, however lesions in enterocytes and their correlation with disease severity and patient prognosis are still unknown. METHODS: SARS-CoV-2 patients were enrolled in five medical centres in the Sao Paulo State, Brazil. Clinical characteristics and laboratory findings of patients were recorded. At admission, 7th and 14th day of hospitalisation, plasma and urine samples were collected. The levels of cytokines (IFN-I³, IL-6 and TNF-α) and the biomarker intestinal fatty acid-binding protein (I-FABP) were measured. RESULTS: COVID-19 patients displayed ≈48-, 74- and 125-fold increased urinary I-FABP levels at admission (n=283; p

Background : One-anastomosis gastric bypass (OAGB) is a simpler procedure than Roux-en-Y gastric bypass (RYGB); however, biliary reflux can occur and impair outcomes. This study aimed to compare outcomes of OAGB and RYGB. Methods : Twenty patients with morbid obesity were randomized prospectively into two groups: OAGB (n=10) or RYGB (n=10). Quality of life (36-item short-form health survey [SF-36]), satisfaction (Visick scale), and body mass index (BMI) were evaluated before and 6 months after the operation. All patients underwent esophagogastroduodenoscopy with gastric and esophageal mucosal biopsies at 3 and 6 months after their operation. Results : The study found no significant difference in BMI before surgery (OAGB, 43.2 kg/m2; RYGB, 43.1 kg/m2; P=0.90) or at 6 months postoperative (OAGB, 32.1 kg/m2; RYGB, 31.8 kg/m2; P=0.91). There was no significant difference in improvement of quality of life (four SF-36 domains) or satisfaction (P=0.08) between groups at 6 months. There was no statistical difference between gastric (P=0.10) and esophageal (P=0.76) inflammation grade at three or 6 months between the two groups. Conclusion : OAGB and RYGB are equally effective in terms of weight loss, patient satisfaction, and quality of life improvement at 6 months after the procedures. Inflammation grade and cellular damage in the gastric pouch and in the esophagus were similar.

Background No methods exist for confirming nerve ablation in catheter-based renal sympathetic denervation (RDN). Methods We investigated the feasibility of using intravascular ultrasound (IVUS) to locate nerves and observe nerve integrity changes during RDN in a pig. To confirm our observations, we used post-RDN histological sections matched anatomically to the IVUS images. Results IVUS revealed multiple hypoechoic structures along the renal artery, whose locations matched those of nerves in the histological sections. Nerves clustered near the junction between the renal artery and vein. Histology confirmed necrosis of nerve bundles at RDN ablation sites, but no changes in echogenicity were observed using IVUS. Conclusions Although IVUS cannot currently be used to confirm ablation during RDN, it clearly reveals some clusters of renal sympathetic nerves. It remains to be demonstrated how IVUS can guide RDN devices and potentially improve ablation success.

Background: Epigenomic changes occurring during surgery have been neglected in research; diabetes and hypertension can affect the epigenome but little is known about the epigenetics of skeletal muscle (SKM). Methods: DNA methylation was profiled via Illumina MethylationEPIC arrays in SKM samples obtained at the beginning and end of heart surgery with cardiopulmonary bypass. Results: Methylation in patients with hypertension and diabetes was significantly different, more so for uncontrolled diabetes; hypertension alone produced minimal effect. The affected pathways involved IL-1, IL-12, IL-18, TNF-α, IFN-γ, VEGF, NF-κB and Wnt signaling, apoptosis and DNA damage response. Significant changes occurred during surgery and included loci in the Hippo–YAP/TAZ pathway. Conclusion: Cardiopulmonary bypass surgery affects the SKM methylome, and the combination of hypertension and diabetes induces changes in the SKM epigenome in contrast to hypertension alone.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment., Graphical abstract Baicalin exerts its anticancer activity in bladder cancer by inducing ferritin heavy chain 1 (FTH1)-dependent ferroptosis, which will hopefully provide great therapeutic potential for bladder cancer treatment.Image 1

BACKGROUND: Little is known about the impact of implicit bias our trainees experience in the form of role misidentification in the clinical learning environment. ACTIVITY: We surveyed 540 residents and clinical medical students to determine the frequency and impact of role misidentification. RESULTS AND DISCUSSION: Most respondents (85%, n = 162) experienced role misidentification, directly resulting in heightened emotions that led to guarded behavior. An additional indirect impact for trainees is transmitted through frequent non-promotional role misidentification and personalizing the incidents. Women and trainees with marginalized identities had significant impacts. These findings present an opportunity to improve our understanding of the trainee experience. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01475-9.

Purpose: The purpose of this study was to examine the differences in the medical students’ satisfaction on online flipped learning by the learning style.Methods: A total of 42 second-year medical students were participated in this study. As study tools, Felder and Soloman’s Index of Learning Styles and the Korean Educational Development Institute’s National Assessment of Student Engagement in Learning were utilized. Data analysis was conducted with the Kruskal-Wallis test, a nonparametric statistical method.Results: Results showed that there were statistically significant differences within active–reflective types and sensing–intuitive types. The active–reflective type has been shown to have statistically significant differences for the three effects of learning, such as problem solving and understanding, active participation, and self-directed learning attitudes. For sensing–intuitive type, active participation showed a significant difference from other effects of learning.Conclusion: The learning style is an important concept in understanding the diverse ways in which students process and absorb new information. Hence research is needed to conduct successful small group activities through online. In the future, it is necessary to find the factors that can lead to successful online classes in medical schools.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55–62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s11046-021-00610-9.

Background &Aims Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials of vaccine studies against SARS-CoV-2. Although clinical efficacy of COVID vaccines in immunocompromised patients was unknown, many societies had recommended vaccination of this highly vulnerable patient population. Methods In this prospective study, we determined antibody (Ab) response to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis. Results Of the 233 patients enrolled so far, 62 had LT, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Ab titers were defined as undetectable (250 U/mL). Of the 62 patients who had LT, Ab levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47 - 212 U/mL) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable Ab and 15 had suboptimal (median titer 41.3, range 0.49 - 221 U/L) response. Of the 92 patients without cirrhosis, four had undetectable Ab and 19 had suboptimal (median titer 95.5, range 4.9 - 234 U/L) Ab response. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. Conclusions Poor antibody response after SARS-CoV-2 vaccination was seen in 61% of LT recipients and 24% of those with CLD. Lay summary The clinical efficacy of COVID vaccines in immunocompromised patients is unknown. We did a prospective study to evaluate immune responses to COVID vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 subjects with cirrhosis and 92 subjects with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody response (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody response when adjusted for other factors., Graphical abstract

Manipulation of perinatal diets, such as supplementing feed with rumen-protected glucose (RPG), has been positively regarded as a strategy to improve milking performance. This study was conducted to assess the effects of RPG on the fermentation profiles, resident microbiota and mucosal immunity in the cecum. Ten Holstein dairy cows were randomly assigned to either a 25 g/kg RPG diet (DM basis) or a 11 g/kg coating fat diet (control, CON). Compared with the CON group, the acetate-to-propionate ratio was lower in the RPG group. Gene expression analysis indicated that RPG supplementation tended to upregulate the expression of Na+/H+ hydrogen exchanger 3 (NHE3) (P = 0.076). RPG supplementation downregulated the expression of genes involved in self-rehabilitation such as matrix metalloproteinase 1 (MMP1), MMP3, MMP9 and MMP13. Additionally, the mRNA expression of genes involved in immunity including Toll-like receptors (TLR4, TLR6 and TLR7) and proinflammatory cytokines (immune interferon gamma [IFNG] and interleukins interleukin 17A [IL17F], IL17A, IL22), was downregulated by RPG supplementation. Nonetheless, no differences existed in the bacterial copy number and beta diversity between the 2 groups. Overall, supplementation with RPG would probably cause a shift towards propionate production in the cecal digesta, and promote the immune homeostasis of the cecal mucosa in transition dairy cows. Our results extended the basic understanding of RPG supplementation and utilization in transition dairy cows in terms of host microbe interplay in the cecum.

Educational escape rooms (EERs) are live-action, team-based games used to teach content-related and generic knowledge and skills. Instead of students just playing the EER, we believed that giving them the opportunity to create their own EERs would augment the learning effects of this teaching method. We report on the feasibility, evaluation, and lessons learned of our assignment on an opioid epidemic-based EER. This original teaching method appealed to most students, but the workload was evaluated to be too high. Our lessons learned include the need for sufficient (extrinsic) motivation, careful explanation of the assignment, and small group sizes.

Purpose: This study aimed to investigate the differences in the perception between professors and students regarding medical educators’ roles and discuss their desirable roles.Methods: A survey was administered to 116 professors and 379 students of the medical colleges from Dankook University and Hallym University. The subjects were given a self-created questionnaire designed to measure their perception of medical educators’ roles.Results: First, “student performance management” for professors and “teaching skill development” for students were recognized as the most essential medical educators’ role. Second, females students perceived the roles to be more important than males in eight of 10 roles.Conclusion: First, “student performance management” for professors and “teaching skill development” for students were recognized as the most essential medical educators’ role. Second, females students perceived the roles to be more important than males in eight of 10 roles.

Colorectal cancer (CRC) incidence and mortality are rising in individuals under age 50, termed early age onset (EAO) CRC. Lower endoscopy is recommended for all patients with unexplained iron deficiency anemia (IDA) or hematochezia to assess the EAO-CRC. For those without symptoms, professional societies recommend decreasing the age to start screening from 50 to 45. Primary care provider (PCP) knowledge and practices around EAO-CRC risk assessment and screening are unknown. We conducted a survey study in May, 2020 of multi-specialty PCPs from three large medical systems to assess PCP knowledge, risk stratification practices and barriers/facilitators they face to offer CRC screening in patients < 50. We conducted univariate analysis to assess factors associated with knowledge and diagnostic practices. Response rate was 27.7% (196/708). Although 77.6% of respondents were aware that EAO-CRC incidence is increasing, only 42.9% knew that EAO-CRC mortality is also increasing. Of note, 91.8% recommend starting average risk screening at age 50. For 40- to 49-year-old patients present with unexplained IDA or hematochezia, 71.9% and 50.5% of respondents, respectively, recommend a diagnostic colonoscopy. Trainees were less likely to be aware of rising EAO-CRC mortality (odds ratio, 0.42; 95% CI, 0.21 to 0.82) and non-internal medicine providers were less likely to recommend CRC screening in those with a first-degree relative with CRC (odds ratio, 0.82; 95% CI, 0.72 to 0.93). Ongoing education efforts will be required to improve recognition and management of high-risk symptoms, particularly among non-internists and trainees.

Anti-Black racism has contributed to significant disparities in health status for Black individuals in Canada. Dermatology is one area where these health disparities are evident. Lack of appropriate medical education regarding dermatologic conditions in persons of color has been associated with worse health outcomes. This project improved representation in a preclerkship dermatology medical school curriculum, through a constructivist approach, by adding images and discussion points of skin diseases in persons of color to existing teaching sessions. Student evaluations demonstrated strong agreement with improved exposure to images of dark skin and improved comfort in identifying skin conditions in persons of color. This intervention represents an effective approach to updating representation in the dermatology curriculum.

Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P

Grossing of surgical pathology specimens is a complex task, which may be challenging to master correctly. Despite the growing use of digital technology in other aspects of surgical pathology, little has been done so far to modernize the documentation of grossing. We used a portable video camera ("GoPro") to document different grossing procedures. The video material may be used for teaching purposes or might enhance the more commonplace macroscopic description by adding another dimension. Furthermore, video documentation may encourage the discussion of upcoming clinical questions or help rectify some possible initial impreciseness.

Emerging reports of SARS‐CoV‐2 breakthrough infections entail methodical genomic surveillance for determining the efficacy of vaccines. This study elaborates genomic analysis of isolates from breakthrough infections following vaccination with AZD1222/Covishield and BBV152/Covaxin. Variants of concern B.1.617.2 and B.1.1.7 responsible for cases surge in April–May 2021 in Delhi, were the predominant lineages among breakthrough infections.

Dissolved carbon dioxide (dCO(2)) stripping from a model solution containing sake flavor by feeding gaseous nitrogen (N(2)) using a microbubble (MB) generator was investigated. The effect of dCO(2) stripping by N(2)MB increased significantly with increasing flow rate of gaseous N(2) from 100 to 200 mL/min. dCO(2) stripping from 3,000 mL of the model solution was achieved by feeding N(2)MB at a flow rate of 200 mL/min for 4 min. Volatile components from model solution containing sake flavor were hardly reduced even after feeding N(2)MB at a flow rate of 200 mL/min for 15 min by cooling to below 10 °C. On the other hand, non-microbubbled gaseous N(2) at a flow rate of 200 mL/min was not very effective in stripping dCO(2). Therefore, the use of N(2)MB with cooling to below 10 °C was effective in stripping dCO(2) while maintaining the volatile components in model solution containing sake flavor.

The COVID-19 pandemic has significantly impacted medical education; thus, there is a need to better understand the effectiveness of virtual learning compared to in-person learning. This is a single-center, cross-sectional study of first-year medical students who attended a gastroenterology simulated clinic activity in person in 2018 and 2019 or virtually in 2020. Participants were surveyed on the activity’s relevance and effectiveness. Students’ assessment of the virtual clinic’s effectiveness and relevance was not significantly different from the in-person version of the activity. In addition, most students rated the virtual clinic as effective for learning about telemedicine.

Purpose Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19). Although our understanding of the pathogenesis of COVID-19 has rapidly evolved, much of the focus has been on the immune mechanisms underlying COVID-19. In addition to immune dysfunction, vascular injury is also associated with COVID-19 and is a major driver of clinical deterioration in SARS-CoV-2 infections. The glycocalyx (GAC), a sugar-based shell that surrounds all mammalian cells, is an important regulator of vascular and immune responses. In sepsis, vascular dysfunction contributes to acute respiratory distress syndrome (ARDS) by altering vessel integrity, promoting thrombosis, and accelerating inflammation, all of which are also present in COVID-19. Observational studies in sepsis have found an association between levels of circulating GAC degradation products with both organ dysfunction and mortality. Although vascular dysfunction is a hallmark of COVID-19, it remains unclear whether GAC disruption occurs in COVID-19 and if GAC disruption contributes to the clinical progression of COVID-19. Methods In this prospective cohort study, we measured the GAC components syndecan-1 (SDC1) and hyaluronan (Hyal) along with inflammatory cytokines in 12 hospitalized COVID-19 patients and 8 healthy controls (HC). Results In agreement with other studies, we found that inflammatory cytokines are elevated in hospitalized COVID-19 patients compared with HC [median (IQR), all units picograms per milliliter: IL-6 4.65 (3.32–9.16) vs 0.69 (0.55–0.89), p p p = 0.036; Hyal: 26.41 (16.4–35.1) vs 3.01 (1.66–4.61), p Conclusion We propose that GAC markers offer insights into the pathobiology of COVID-19, potentially guide therapeutic approaches, and could aid in early risk stratification that is particularly beneficial in phasic diseases such as COVID-19.

Ouabain is a cardiac steroid hormone with immunomodulatory effects. It inhibits neutrophils migration induced by different stimuli, but little is known about the mechanisms involved in this effect. Thus, the aim of this study was to evaluate the ouabain effect on chemotactic signaling pathways in neutrophils. For that, mice neutrophils were isolated from bone marrow, treated with ouabain (1, 10, and 100 nM) for 2 h, submitted to transwell chemotaxis assay and flow cytometry analysis of Akt, ERK, JNK, and p38 phosphorylation induced by zymosan. Ouabain treatment (1, 10 and, 100 nM) reduces neutrophil chemotaxis induced by chemotactic peptide fMLP, but this substance did not inhibit Akt, ERK, and JNK activation induced by zymosan. However, ouabain (1 and 10 nM) reduced p38 phosphorylation in zymosan-stimulated neutrophils. These results suggest that ouabain may interfere in neutrophil migration through p38 MAPK inhibition.

Didelphis marsupialis is a primary reservoir of Trypanosoma cruzi, etiologic agent of American Trypanosomiasis-AT or Chagas Disease-CD, in America. Some findings of Trypanosoma rangeli have been recorded in this mammal, in sympatry with T. cruzi. In Los Montes de María, Bolívar, Colombian Caribbean, triatomine insects and potential parasite host has been registered, but little is known about the relationship between these parasites and D. marsupialis. We investigated the natural trypanosomatids infection rate in D. marsupialis, applying a parasitological and molecular diagnosis. Twenty D. marsupialis was investigated between 2018 and 2019 using 21 Tomahawk® traps placed on the sylvatic/domestic corridors. Blood was drawn by cardiopuncture after sedation. An aliquot of blood samples was cultured in Novy, Nicolle, McNeal/Roswell Park Memorial Institute medium at 24 °C/60 days for the detection of motile trypomastigotes. Parasite DNA was obtained by salting out methods from positive blood cultures. Trypanosomatids diagnosis was done by Polymerase Chain Reaction-sequencing of V7V8 region of 18S ribosomal RNA (18S-rRNA) gene. Amplicons were sequenced, and consensus sequences were aligned with reference sequences from GenBank. Four isolates corresponded to T. rangeli (20%) and one to T. cruzi (5%). The natural infection of D. marsupialis by T. rangeli and T. cruzi constitutes the first record of these parasites in didelphids in Los Montes de María and the first record of T. rangeli in this marsupial, in the Colombian Caribbean.

Objectives This study aimed to explore the experiences and views of domiciliary coronavirus disease (COVID-19) patients towards pharmaceutical care services provided during their infection. Methods This was a single-centred observational study conducted among home-treated COVID-19 patients (n = 500), who were tested positive for COVID-19 in a medical centre in Lebanon. Key findings Out of the 500 home-treated COVID-19 patients invited to participate in the study, 279 patients completed the questionnaire. Although the participants had a good view of pharmacists caring for COVID-19 patients (mean view score: 17.79/25), their treatment experiences were unsatisfactory (mean experience score: 1.51/4). Conclusions COVID-19 patients reported minimal involvement of pharmacists in their treatment. Therefore, in response to the COVID-19 pandemic, healthcare authorities should intervene in restructuring, guiding and reviewing unrealized new pharmaceutical services to COVID-19 outpatients.

Aerosolization of SARS-CoV-2 by COVID-19 patients can put healthcare workers and susceptible individuals at risk of infection. Air sampling for SARS-CoV-2 has been conducted in healthcare settings, but methods vary widely and there is need for improvement. The objective of this study was to evaluate the feasibility of using a high-volume filter sampler, BioCapture z720, to detect SARS-CoV-2 in COVID-19 patient rooms in a medical intensive care unit, a dedicated COVID-19 ward, and at nurses’ stations. In some locations, the BioSpot-VIVAS, known for high efficiency in the collection of virus-containing bioaerosols, was also operated. The samples were processed for SARS-CoV-2 RNA with multi-plex nested polymerase chain reaction. One of 28 samples collected with the high-volume filter sampler was positive for SARS-CoV-2; all 6 samples collected with BioSpot-VIVAS were negative for SARS-CoV-2. The high-volume filter sampler was more portable and less intrusive in patient rooms than the BioSpot-VIVAS, but limits of detection remain unknown for this device. This study will inform future work to evaluate the reliability of these types of instruments and inform best practices for their use in healthcare environments for SARS-CoV-2 air sampling.

At Virginia Tech Carilion School of Medicine, we implemented a new strategy to organize the longitudinal delivery of pharmacology, leveraging elements of spaced repetition and spiral design. Our innovative model focused on generating cognitive frameworks in large group sessions, providing a scaffold to associate key aspects of individual drugs using specific objectives in problem-based learning. The design enhanced both student satisfaction and summative performance on pharmacology content on end of Block National Board of Medical Examiners exams. By taking a new approach, we were able to focus student learning, reduce the extraneous load and retain rigor and content volume. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01461-1.