The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 ...dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.
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•SARS-CoV-2-infected ferrets exhibit elevated body temperature and virus replication•SARS-CoV-2 is shed in nasal washes, saliva, urine and feces•SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact•SARS-CoV-2 infection leads acute bronchiolitis in infected ferrets
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spreads, leading to a pandemic infection. Kim et al. show that ferrets are highly susceptible to SARS-CoV-2 infection and effectively transmit the virus by direct or indirect contact, recapitulating human infection and transmission.
Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are ...produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. α-Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of
,
,
,
,
and
genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.
Parkinson's disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting ...evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of
PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain. Notably, the inflammation-related expression of miR-155-5p was significantly upregulated in the proximal colon, midbrain, and striatum of PD-like mice. PS128 reduced the level of miR-155-5p, whereas it increased the expression of suppressor of cytokine signaling 1 (SOCS1), a direct target of miR-155-5p and a critical inhibitor of the inflammatory response in the brain. Alteration of the fecal microbiota in PD-like mice was partially restored by PS128 administration. Among them,
,
_6,
, and
were statistically correlated with the improvement of rotenone-induced motor deficits and the expression of miR-155-5p and SOCS1. Our findings suggested that PS128 ameliorates motor deficits and exerts neuroprotective effects by regulating the gut microbiota and miR-155-5p/SOCS1 pathway in rotenone-induced PD-like mice.
Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir ...grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients.
ClinicalTrials.gov NCT02361372.
Introduction
Kefir is an acidic and alcoholic fermented milk product with multiple health‐promoting benefits. A previous study demonstrated that kefir enhanced calcium absorption in intestinal Caco‐2 ...cells. In this study, kefir‐fermented peptide‐1 (KFP‐1) is isolated from the kefir peptide fraction, and its function as a calcium‐binding peptide is characterized.
Methods and Results
KFP‐1 was identified as a 17‐residue peptide with a sequence identical to that of κ‐casein (residues 138–154) in milk protein. KFP‐1 is demonstrated to promote calcium influx in Caco‐2 and IEC‐6 small intestinal cells in a concentration‐dependent manner. TRPV6, but not L‐type voltage‐gated calcium channels, is associated with the calcium influx induced by KFP‐1. An in vitro calcium binding assay indicates that the full‐length KFP‐1 peptide has a higher calcium‐binding capacity than the two truncated KFP‐1 peptides, KFP‐1∆C5 and KFP‐1C5. Alexa Fluor 594 labeling shows that KFP‐1 is taken up by Caco‐2 cells and interacts with calcium ions and TRPV6 protein. Moreover, KFP‐1 is found moderately resistant to pepsin and pancreatin digestions and enhanced calcium uptake by intestinal enterocytes in vivo.
Conclusion
These data suggest that KFP‐1, a novel calcium‐binding peptide, binds extracellular calcium ions and enters Caco‐2 and IEC‐6 cells, and promotes calcium uptake through TRPV6 calcium channels. The present study is of great importance for developing kefir‐derived metal ion‐binding peptides as functional nutraceutical additives.
Proposed mechanism of action of KFP‐1 for promoting calcium influx in intestinal epithelial cells. Based on the experimental data, it is hypothesized that KFP‐1 increased of intracellular calcium uptake in Caco‐2 cell through TRPV6 calcium channel, but not L‐type VGCC. Therefore, KFP‐1 can transmit dietary calcium from the luminal space of intestinal tract to the circulation system.
Human papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia ...(HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new SN group) and those who had undergone conization without hysterectomy (surveillance previous SP group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need.
What's new?
High‐grade cervical intraepithelial neoplasia (HG‐CIN), a cervical carcinoma precursor, frequently is caused by high‐risk human papillomavirus (hr‐HPV) infection. HG‐CIN can be treated by cervical conization, though the procedure does not eradicate hr‐HPV, potentially enabling CIN recurrence. Here, in Taiwanese patients, investigation of HPV genotype changes in relation to HG‐CIN status after conization shows that 77.4 percent of patients with recurrent CIN 2 grade or worse (CIN2+) after conization had persistent type‐specific HPV infections. Vaccination against the remaining high‐risk HPVs prevented recurrent CIN2+ in only 8.3 percent of patients, revealing an unmet need for effective therapeutic vaccines.
Background
Robot-assisted gastrectomy (RAG) has been increasingly used for the treatment of advanced gastric cancer (AGC), and many advantages over laparoscopy-assisted gastrectomy (LAG) have been ...reported. However, its postgastrectomy complications still under investigation and the results remain controversial. This study aimed to objectively assess the incidence and severity of complications following RAG vs. LAG using Clavien–Dindo (C–D) classification and to identify risk factors related to complications.
Methods
Five hundred and twenty-seven patients with AGC who underwent RAG or LAG between January 2016 and May 2018 were enrolled in this study. Complications were categorized according to the C–D classification. The complications following RAG and LAG were compared using one-to-one propensity score matching (PSM) analysis and subgroup analyses. Logistic regression analyses were performed to identify risk factors related to complications.
Results
RAG was performed in 251 patients (47.6%) and LAG in 276 patients (52.4%). Before PSM, the RAG group had a smaller tumour size (
P
= 0.004) and less patients with previous abdominal operation (
P
= 0.013). After PSM, a well-balanced cohort of 446 patients (223 in each group) was further analyzed. Of interest, the incidence of overall and severe complications (C–D grade ≥ IIIa) following the RAG group were significantly fewer than the LAG group (overall, 24.5% vs. 18.8%,
P
< 0.001; severe, 8.9% vs. 17.5%,
P
= 0.002). Subgroup analyses showed statistically significant difference were also observed in most stratified parameters. Multivariable analysis identified age ≥ 65 years, total gastrectomy, stage T3–T4a, stage II–III, and operation time ≥ 250 min as independent predictors of overall complications. Additionally, age ≥ 65 years, stage II–III, and operation time ≥ 250 min were confirmed as independent risk factors for severe complications.
Conclusions
RAG with D2 lymphadenectomy is feasible and safe for the treatment of AGC in terms of the lower incidence and severity of complications.
Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of 1-week amphotericin B ...deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV-CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV-CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + Azole (OR = 1.1E-12, 95% CIs = 1.3E-41 to 0.06) comparing to AmphB + 5-FC. The current NMA provides evidence that AmphB + 5-FC + Azole are superior to all the investigated treatments for induction regimen in HIV-CM patients.
Objective
This study aims to develop an artificial intelligence‐based method to screen patients with left ventricular ejection fraction (LVEF) of 50% or lesser using electrocardiogram (ECG) data ...alone.
Methods
Convolutional neural network (CNN) is a class of deep neural networks, which has been widely used in medical image recognition. We collected standard 12‐lead ECG and transthoracic echocardiogram (TTE) data including the LVEF value. Then, we paired the ECG and TTE data from the same individual. For multiple ECG‐TTE pairs from a single individual, only the earliest data pair was included. All the ECG‐TTE pairs were randomly divided into the training, validation, or testing data set in a ratio of 9:1:1 to create or evaluate the CNN model. Finally, we assessed the screening performance by overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value.
Results
We retrospectively enrolled a total of 26 786 ECG‐TTE pairs and randomly divided them into training (n = 21 732), validation (n = 2 530), and testing data set (n = 2 530). In the testing set, the CNN algorithm showed an overall accuracy of 73.9%, sensitivity of 69.2%, specificity of 70.5%, positive predictive value of 70.1%, and negative predictive value of 69.9%.
Conclusion
Our results demonstrate that a well‐trained CNN algorithm may be used as a low‐cost and noninvasive method to identify patients with left ventricular dysfunction.
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