The long-term risks of uninephrectomy in the living-related kidney donors are of concern. We studied the outcome in living-related allograft donors after donation who have been followed up at ...Princess Margaret Hospital from 1980 to 1996 by comparing renal function, blood pressure and proteinuria.
Ninety-one allograft donors, aged from 19 to 59 years (mean 36.61 ±7.63 years; 43 males and 48 females) were followed up for 1 to 17 years (mean 5.5 ±2.5 years). After nephrectomy, serum creatinine rose by 46.2% from baseline 81.3 ±13.0 μmol/L to 118.9 ±32.9 μmol/L at 3 months (p < 0.001). In 58 of the 91 patients who were followed up for more than 3 years, serum creatinine decreased to 99.7 ±13.2 μmol/L (p < 0.05) at the end of the study period as compared with serum creatinine at 3-month follow-up. Creatinine clearance also decreased from 107.6 ±24.0 ml/min before nephrectomy to 78.8 ±15.7 ml/min at 1-year follow-up (p < 0.001). Then it became 79.8 ±18.3 ml/min at the latest follow-up (p = 0.599). Systolic blood pressure increased from 114.2 ±8.6 mmHg before nephrectomy to 120.0 ±10.4 mmHg (p < 0.001) at the latest follow-up after nephrectomy. Meanwhile, the diastolic blood pressure rose from 71.1 ±7.2 mmHg at baseline to 73.1 ±8.3 mmHg at the end of the study period (p = 0.091). The mean arterial blood pressure increased from 85.5 ±7.0 mmHg to 88.7 ±8.1 mmHg at the latest follow-up (p > 0.005). Proteinuria increased from 65 ±55 mg/day to 96 ±55 mg/day at the latest follow-up (p = 0.142).
In conclusion, there was no progression of renal dysfunction in renal allograft donor after nephrectomy. Serum creatinine even improved significantly at the end of the study period as compared with that at 3-month postnephrectomy. Systolic blood pressure and mean arterial blood pressure had a small increment at the latest follow-up. The prevalence of hypertension was 4.4%. Moreover, proteinuria did not show a significant increase after donation.
The field of cancer genomics and transcriptomics has evolved from targeted profiling to swift sequencing of individual tumor genome and transcriptome. The steady growth in genome, epigenome, and ...transcriptome datasets on a genome-wide scale has significantly increased our capability in capturing signatures that represent both the intrinsic and extrinsic biological features of tumors. These biological differences can help in precise molecular subtyping of cancer, predicting tumor progression, metastatic potential, and resistance to therapeutic agents. In this review, we summarized the current development of genomic, methylomic, transcriptomic, proteomic and metabolic signatures in the field of cancer research and highlighted their potentials in clinical applications to improve diagnosis, prognosis, and treatment decision in cancer patients.
Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. ...Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.
Lycium Barbarum Polysaccharides (LBP) are the active components of Wolfberry (a traditional Chinese medicine) which has long been used for improving visual function. This study aims to investigate ...localized changes of retinal function in a partial optic nerve transection (PONT) model, and effects of LBP on visual function. The multifocal electroretinograms (mfERG) were obtained from 30 eyes of 30 Sprague-Dawley rats. The rats were divided into 6 groups (five treatment groups and one control group). Starting from the first day of the experiment, the rats in the (PONT+LBP) group and the (LBP) group were dosed with LBP; rats in the (PONT+PBS (phosphate buffered saline)) group and the (PBS) group were dosed with PBS via nasogastric tube every day until euthanized. The dorsal part of the optic nerve was transected in the (PONT), (PONT+LBP) and (PONT+PBS) groups at the end of week 1 (day 7 after LBP or PBS feeding began). The mfERG was measured at three time points: week 2, week 3 and week 5. Significant reduction of P1 and PhNR amplitudes of the mfERG were observed in all retinal regions a week after PONT. Feeding with LBP prior to PONT preserved retinal function. All mfERG responses returned to the normal range in the superior retina, which corresponds to the transected dorsal region of the optic nerve, while most of the inferior retinal responses were significantly increased at week 4 after PONT. The ventral part of the retina had secondary degeneration which was not only limited to the ganglion cell layer, but is a widespread effect affecting the outer retina. LBP altered the functional reduction caused by PONT by regulating the signal from the outer retina.
Background & Aims Little is known about the efficacy of H2 -receptor antagonists in preventing recurrence of aspirin-related peptic ulcers. We compared the efficacy of high-dose famotidine with that ...of pantoprazole in preventing recurrent symptomatic ulcers/erosions. Methods We performed a randomized, double-blind, controlled trial of 160 patients with aspirin-related peptic ulcers/erosions, with or without a history of bleeding. Patients were given either famotidine (40 mg, morning and evening) or pantoprazole (20 mg in the morning and placebo in the evening). All patients continued to receive aspirin (80 mg daily). The primary end point was recurrent dyspeptic or bleeding ulcers/erosions within 48 weeks. Results A total of 130 patients (81.1%) completed the study; 13 of 65 patients in the famotidine group reached the primary end point (20.0%; 95% one-sided confidence interval CI for the risk difference, 0.1184–1.0) compared with 0 of 65 patients in the pantoprazole group ( P < .0001, 95% one-sided CI for the risk difference, 0.1184–1.0). Gastrointestinal bleeding was significantly more common in the famotidine group than the pantoprazole group (7.7% 5/65 vs 0% 0/65; 95% one-sided CI for the risk difference, 0.0226–1.0; P = .0289), as was recurrent dyspepsia caused by ulcers/erosions (12.3% 8/65 vs 0% 0/65; 95% one-sided CI for the risk difference, 0.0560–1.0; P = .0031). No patients had ulcer perforation or obstruction. Conclusions In patients with aspirin-related peptic ulcers/erosions, high-dose famotidine therapy is inferior to pantoprazole in preventing recurrent dyspeptic or bleeding ulcers/erosions.
Few data are available about the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission.
To investigate whether hand hygiene and use of facemasks prevents ...household transmission of influenza.
Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893)
Households in Hong Kong.
407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.
Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.
Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.
Sixty (8%) contacts in the 259 households had RT-PCR-confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR-confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 95% CI, 0.13 to 0.87). Adherence to interventions varied.
The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.
Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.
Centers for Disease Control and Prevention.
SARS-CoV-2 has evolved rapidly into several genetic clusters. However, data on mutations during the course of infection are scarce. This study aims to determine viral genome diversity in serial ...samples of COVID-19 patients.
Targeted deep sequencing of the spike gene was performed on serial respiratory specimens from COVID-19 patients using nanopore and Illumina sequencing. Sanger sequencing was then performed to confirm the single nucleotide polymorphisms.
A total of 28 serial respiratory specimens from 12 patients were successfully sequenced using nanopore and Illumina sequencing. A 75-year-old patient with severe disease had a mutation, G22017T, identified in the second specimen. The frequency of G22017T increased from ≤5% (nanopore: 3.8%; Illumina: 5%) from the first respiratory tract specimen (sputum) to ≥60% (nanopore: 67.7%; Illumina: 60.4%) in the second specimen (saliva; collected 2 days after the first specimen). The difference in G22017T frequency was also confirmed by Sanger sequencing. G22017T corresponds to W152L amino acid mutation in the spike protein which was only found in <0.03% of the sequences deposited into a public database. Spike amino acid residue 152 is located within the N-terminal domain, which mediates the binding of a neutralizing antibody.
A spike protein amino acid mutation W152L located within a neutralizing epitope has appeared naturally in a patient. Our study demonstrated that monitoring of serial specimens is important in identifying hotspots of mutations, especially those occurring at neutralizing epitopes which may affect the therapeutic efficacy of monoclonal antibodies.
To investigate (1) the effects of indoor incense burning upon cognition over 3 years; (2) the associations between indoor incense burning with the brain's structure and functional connectivity of the ...default mode network (DMN); and (3) the interactions between indoor incense burning and vascular disease markers upon cognitive functions. Community older adults without stroke or dementia were recruited (n = 515). Indoor incense use was self-reported as having burnt incense at home ≥ weekly basis over the past 5 years. Detailed neuropsychological battery was administered at baseline (n = 227) and the Montreal Cognitive Assessment at baseline and year 3 (n = 515). MRI structural measures and functional connectivity of the DMN were recorded at baseline. Demographic and vascular risk factors and levels of outdoor pollutants were treated as covariates. Indoor incense burning was associated with reduced performance across multiple cognitive domains at baseline and year 3 as well as decreased connectivity in the DMN. It interacted with diabetes mellitus, hyperlipidemia and white matter hyperintensities to predict poorer cognitive performance. Indoor incense burning is (1) associated with poorer cognitive performance over 3 years; (2) related to decreased brain connectivity; and (3) it interacts with vascular disease to predispose poor cognitive performance.
Viral genomic surveillance is vital for understanding the transmission of COVID-19. In Hong Kong, breakthrough outbreaks have occurred in July (third wave) and November (fourth wave) 2020. We used ...whole viral genome analysis to study the characteristics of these waves.
We analyzed 509 SARS-CoV-2 genomes collected from Hong Kong patients between 22nd January and 29th November, 2020. Phylogenetic and phylodynamic analyses were performed, and were interpreted with epidemiological information.
During the third and fourth waves, diverse SARS-CoV-2 genomes were identified among imported infections. Conversely, local infections were dominated by a single lineage during each wave, with 96.6% (259/268) in the third wave and 100% (73/73) in the fourth wave belonging to B.1.1.63 and B.1.36.27 lineages, respectively. While B.1.1.63 lineage was imported 2 weeks before the beginning of the third wave, B.1.36.27 lineage has circulated in Hong Kong for 2 months prior to the fourth wave. During the fourth wave, 50.7% (37/73) of local infections in November was identical to the viral genome from an imported case in September. Within B.1.1.63 or B.1.36.27 lineage in our cohort, the most common non-synonymous mutations occurred at the helicase (nsp13) gene.
Although stringent measures have prevented most imported cases from spreading in Hong Kong, a single lineage with low-level local transmission in October and early November was responsible for the fourth wave. A superspreading event or lower temperature in November may have facilitated the spread of the B.1.36.27 lineage.
Richard and Carol Yu, Michael Tong, and the Government Consultancy Service (see acknowledgments for full list).
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome ...of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil MMF, lopinavir/ritonavir, and interferon- beta 1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon- beta 1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores arrowdown50.9%-95.0% and arrowdownweight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung (arrowdown0.59-1.06 log10 copies/glyceraldehyde 3-phosphate dehydrogenase GAPDH; P < .050) and extrapulmonary (arrowdown0.11-1.29 log10 copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads (arrowup0.15-0.54 log10 copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0-33% (lopinavir/ritonavir-treated and interferon- beta 1b-treated). Lopinavir/ritonavir and interferon- beta 1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used.
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