Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy.

Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.

The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.

Harnessing the Noncanonical Keap1-Nrf2 Pathway for Human Cytomegalovirus Control.

Host-derived cellular pathways can provide an unfavorable environment for virus replication. These pathways have been a subject of interest for herpesviruses, including the betaherpesvirus human cytomegalovirus (HCMV). Here, we demonstrate that a compound, ARP101, induces the noncanonical sequestosome 1 (SQSTM1)/p62-Keap1-Nrf2 pathway for HCMV suppression. ARP101 increased the levels of both LC3 II and SQSTM1/p62 and induced phosphorylation of p62 at the C-terminal domain, resulting in its increased affinity for Keap1. ARP101 treatment resulted in Nrf2 stabilization and translocation into the nucleus, binding to specific promoter sites and transcription of antioxidant enzymes under the antioxidant response element (ARE), and HCMV suppression. Knockdown of Nrf2 recovered HCMV replication following ARP101 treatment, indicating the role of the Keap1-Nrf2 axis in HCMV inhibition by ARP101. SQSTM1/p62 phosphorylation was not modulated by the mTOR kinase or casein kinase 1 or 2, indicating ARP101 engages other kinases. Together, the data uncover a novel antiviral strategy for SQSTM1/p62 through the noncanonical Keap1-Nrf2 axis. This pathway could be further exploited, including the identification of the responsible kinases, to define the biological events during HCMV replication. IMPORTANCE Antiviral treatment for human cytomegalovirus (HCMV) is limited and suffers from the selection of drug-resistant viruses. Several cellular pathways have been shown to modulate HCMV replication. The autophagy receptor sequestosome 1 (SQSTM1)/p62 has been reported to interact with several HCMV proteins, particularly with components of HCMV capsid, suggesting it plays a role in viral replication. Here, we report on a new and unexpected role for SQSTM1/p62, in HCMV suppression. Using a small-molecule probe, ARP101, we show SQSTM1/p62 phosphorylation at its C terminus domain initiates the noncanonical Keap1-Nrf2 axis, leading to transcription of genes under the antioxidant response element, resulting in HCMV inhibition in vitro. Our study highlights the dynamic nature of SQSTM1/p62 during HCMV infection and how its phosphorylation activates a new pathway that can be exploited for antiviral intervention.

Long stem revision versus short stem revision with plate osteosynthesis for Vancouver type B2 periprosthetic femoral fracture: a comparative study of eighty five cases.

PURPOSE: Periprosthetic femoral fractures (PPFs) around the hip are challenging complications in orthopaedic surgery, particularly Vancouver type B2 (VTB2) fractures. The surgical management of these fractures is crucial and depends on various factors. Cementless short taper stem with plate osteosynthesis is an alternative surgical technique. This study aims to compare the outcomes of this surgical technique with revision arthroplasty (RA) with long stem in the treatment of VTB2 PPFs. METHODS: This retrospective study was conducted in a single medical institute from February 2010 to May 2019. Patients who had received either total hip arthroplasty or bipolar hemiarthroplasty and subsequently developed a VTB2 PPF were included; patients who sustained intra-operative fractures or received a cemented stem previously were excluded from the analysis. The patients were divided into two groups: group I received RA with cementless long stem, while group II underwent RA with cementless short taper stem with plate osteosynthesis. Demographic data, radiographic and functional outcomes, and complications were analyzed between the two groups. RESULTS: A total of 85 patients diagnosed with VTB2 PPFs were included in the study. There were no significant differences between the two groups in terms of demographic data, including age, gender, mean follow-up times, estimated blood loss, and operative times. The radiographic results showed that there was no significant difference in the incidence of subsidence and implant stability between the two groups. However, group II tended to have less subsidence and periprosthetic osteolysis. Patients in group II had significantly better functional scores (mean Harris hip score: post-operative: 60.2 in group I and 66.7 in group ii; last follow-up: 77.4 in group 1 and 83.2 in group II (both p < 0.05)). There were no significant differences in the overall complication rate, including infection, dislocation, re-fracture, and revision surgery, between the two groups. CONCLUSIONS: Both surgical techniques, cementless long stem and cementless short taper stem with plate osteosynthesis, are effective in the treatment of Vancouver B2 PPFs, with no significant differences in outcomes or complications. However, patients in cementless short taper stem with plate osteosynthesis had better functional scores at both post-operative and the last follow-up.

Comparative Analysis of the Chloroplast Genomes of Eight Species of the Genus Lirianthe Spach with Its Generic Delimitation Implications.

Based on Sima and Lu's system of the family Magnoliaceae, the genus Lirianthe Spach s. l. includes approximately 25 species, each with exceptional landscaping and horticultural or medical worth. Many of these plants are considered rare and are protected due to their endangered status. The limited knowledge of species within this genus and the absence of research on its chloroplast genome have greatly impeded studies on the relationship between its evolution and systematics. In this study, the chloroplast genomes of eight species from the genus Lirianthe were sequenced and analyzed, and their phylogenetic relationships with other genera of the family Magnoliaceae were also elucidated. The results showed that the chloroplast genome sizes of the eight Lirianthe species ranged from 159,548 to 159,833 bp. The genomes consisted of a large single-copy region, a small single-copy region, and a pair of inverted repeat sequences. The GC content was very similar across species. Gene annotation revealed that the chloroplast genomes contained 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes, totaling 130 genes. Codon usage analysis indicated that codon usage was highly conserved among the eight Lirianthe species. Repeat sequence analysis identified 42-49 microsatellite sequences, 16-18 tandem repeats, and 50 dispersed repeats, with microsatellite sequences being predominantly single-nucleotide repeats. DNA polymorphism analysis revealed 10 highly variable regions located in the large single-copy and small single-copy regions, among which rpl32-trnL, petA-psbJ, and trnH-psbA were the recommended candidate DNA barcodes for the genus Lirianthe species. The inverted repeat boundary regions show little variation between species and are generally conserved. The result of phylogenetic analysis confirmed that the genus Lirianthe s. l. is a monophyletic taxon and the most affinal to the genera, Talauma and Dugandiodendron, in Sima and Lu's system and revealed that the genus Lirianthe s. s. is paraphyletic and the genus Talauma s. l. polyphyletic in Xia's system, while Magnolia subsection Gwillimia is paraphyletic and subsection Blumiana polyphyletic in Figlar and Nooteboom's system. Morphological studies found noticeable differences between Lirianthe species in aspects including leaf indumentum, stipule scars, floral orientation, tepal number, tepal texture, and fruit dehiscence. In summary, this study elucidated the chloroplast genome evolution within Lirianthe and laid a foundation for further systematic and taxonomic research on this genus.

The Association between Red Blood Cell Distribution Width and Mortality Risk after Hip Fracture: A Meta-Analysis.

Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.

The temporal characteristics of the disruption of gut microbiota, serum metabolome, and cytokines by silica exposure in wistar rats.

Silicosis is one of the most frequent, rapidly developing, and lethal types of pneumoconiosis. However, our understanding of the underlying mechanisms of its pathogenesis and progress remains unclear. We investigated the fundamental processes of silicosis incidence and progression using a combination of lung function testing, histopathology, 16 S rRNA, untargeted metabolomics, and cytokine chips at different exposure times (4 or 8 weeks). The results show that silica exposure damages lung tissue reduces lung function, and increases with time. Cytokines with time-specific properties were found in lung lavage fluid: IFN-γ (4 weeks; P＜0.05), TNF-α, M-CSF, GM-CSF (8 weeks; P＜0.01). In addition, silica exposure for different periods interferes to varying degrees with the metabolism of lipids. The composition of the intestinal microbiota changed with increasing exposure time and there were time-specific: Allobaculum, Turicibacter、Jeotgalicoccu、Coprococcus 1 (4 weeks; P＜0.05), Ruminococcaceae NK4A214 group、Ruminiclostridium 5 (8 weeks; P＜0.05). We found strong associations between cytokines, gut microbiota changes, and metabolic disturbances at different exposure times. These results suggest that time-specific changes in crosstalk among cytokines, the gut microbiota, and metabolites may be a potential mechanism for silica-induced lung injury.

First report of Phytopythium vexans causing root rot on Macadamia integrifolia in China.

Soil-borne plant-pathogenic Phytopythium spp. can cause root rot and damping off on important plant species, resulting in serious economic loss. A survey in October 2021 identified soil-borne diseases occurring on Macadamia integrifolia in Yunnan Province, China. Microbes were isolated from necrotic roots of 23 trees with root rot symptoms by growing on cornmeal-based oomycete-selective 3P (Haas 1964) and P5APR (Jeffers and Martin, 1986) media at 24ºC in the dark for 7 days. Of the 56 single-hyphal isolates obtained, 18 were morphologically similar to Phytopythium vexans (van der Plaats-Niterink 1981; de Cock et al. 2015). Isolates LC04 and LC051 were selected for molecular analyses. The internal transcribed spacer (ITS) region and the cytochrome c oxidase subunit II (CoxII) gene were PCR-amplified using universal primers ITS1/ITS4 (White et al. 1990) and oomycete-specific primers Cox2-F/Cox2-RC4 (Choi et al. 2015), respectively. The PCR products were sequenced with the amplification primers and sequences were lodged in Genbank (Accession no. OM346742, OM415989 for ITS, OM453644, OM453643 for CoxII for isolates LC04 and LC051, respectively). The top BLAST hit in the Genbank nr database for all four sequences was Phytopythium vexans (>99% identity). A maximum-likelihood phylogenetic tree was constructed with analogous concatenated ITS and CoxII sequences from either type or voucher specimens of 13 Phytopythium species in the same phylogenetic clade as P. vexans (Table 1; Bala et. al 2010). Isolates LC04 and LC051 grouped most closely to P. vexans, with LC051 basal and sister to LC04 and P. vexans voucher specimen CBS119.80 with 100% support (Fig. 1). Millet seed inoculated with agar pieces colonized by P. vexans LC04 and LC51 was used to fulfill Koch's postulates (Li et al. 2015) in a completely randomized experimental design. Four 6-month-old M. integrifolia var. Keaau (660) seedlings were transplanted into pasteurized commercial potting mix containing 0.5% (w/w) inoculum. Plants were grown in free draining pots and watered once a day. At 14 days post-inoculation, roots were discolored compared to control plants inoculated with millet seed mixed with agar plugs lacking P. vexans (Fig. 2). By 30 days post-inoculation, infected roots were discolored with obvious decay and reduction in root system size. Control plants were symptomless. P. vexans was successfully re-isolated from two lesioned roots from each plant. The infection experiment was done twice, demonstrating that P. vexans LC04 and LC51 caused root disease on M. integrifolia. P. vexans causes root rot, damping-off, crown rot, stem rot or patch canker on economically important trees in many parts of the world, including seven plant species in China (Farr and Rossman 2022). This is the first report of pathogenic P. vexans on M. integrifolia in China. Reports of pathogenic P. vexans on multiple hosts in several parts of the world suggest it should be considered a quarantine risk and included in risk mitigation or pest management plans that include other species of Phytopythium, or species of Pythium or Phytophthora, to which P. vexans has many similarities (de Cock et al. 2015).

Association between adhesive capsulitis and thyroid disease: a meta-analysis.

HYPOTHESIS: Adhesive capsulitis (AC) is a common clinical condition of the shoulders without a clear pathophysiology or etiology. Although thyroid disease has been linked to AC, an appropriate understanding of the disease and its epidemiological evidence are lacking. This metaanalysis investigated the association of AC with thyroid disease and identified which manifestations of thyroid disease contribute to the risk of AC. MATERIALS AND METHODS: The databases of PubMed, Embase, and Scopus were searched for literature retrieval up to September 20, 2022. Articles evaluating the association between AC and any type of thyroid disease were enrolled. Data from studies reporting the prevalence and its 95% confidence interval (CI) were pooled. Subgroup analysis was performed on the different manifestations of thyroid disease. We explored heterogeneity with sensitivity analyses and publication bias with funnel plots and Egger's tests. A trim and fill analysis was conducted if publication bias was found. RESULTS: Results: In total, 10 case-control studies comprising a total of 127,967 patients were included. The prevalence of thyroid disease was significantly higher in patients with AC (odds ratio [OR] = 1.87, 95% CI: 1.37-2.57, P < .0001) than in patients without AC. The results of subgroup analysis indicated significantly higher rates of hypothyroidism (OR = 1.92, 95% CI: 1.09-3.39, P = .02) and subclinical hypothyroidism (OR = 2.56, 95% CI: 1.81-3.63, P < .00001), but not hyperthyroidism (OR = 1.42, 95% CI: 0.63-3.22, P = .40), among patients with AC than among those without AC. CONCLUSIONS: Our meta-analysis demonstrated that thyroid disease, especially when presenting as hypothyroidism or subclinical hypothyroidism, is associated with an increased risk of AC. Evidence for an association between hyperthyroidism and AC was not found, although this may be due to the lack of related studies. Further research on the pathogeneses of and relationship between these two diseases is warranted.

Association of Coffee and Tea Intake with Bone Mineral Density and Hip Fracture: A Meta-Analysis.

Background and Objectives: Osteoporosis is characterized by low bone mass and high bone fragility. Findings regarding the association of coffee and tea intake with osteoporosis have been inconsistent. We conducted this meta-analysis to investigate whether coffee and tea intake is associated with low bone mineral density (BMD) and high hip fracture risk. Materials and Methods: PubMed, MEDLINE, and Embase were searched for relevant studies published before 2022. Studies on the effects of coffee/tea intake on hip fracture/BMD were included in our meta-analysis, whereas those focusing on specific disease groups and those with no relevant coffee/tea intake data were excluded. We assessed mean difference (MD; for BMD) and pooled hazard ratio (HR; for hip fracture) values with 95% confidence interval (CI) values. The cohort was divided into high- and low-intake groups considering the thresholds of 1 and 2 cups/day for tea and coffee, respectively. Results: Our meta-analysis included 20 studies comprising 508,312 individuals. The pooled MD was 0.020 for coffee (95% CI, -0.003 to 0.044) and 0.039 for tea (95% CI, -0.012 to 0.09), whereas the pooled HR was 1.008 for coffee (95% CI, 0.760 to 1.337) and 0.93 for tea (95% CI, 0.84 to 1.03). Conclusions: Our meta-analysis results suggest that daily coffee or tea consumption is not associated with BMD or hip fracture risk.

Effect of different injection rates and doses of contrast medium on the image quality of computed tomographic angiography in African grey parrots (Psittacus erithacus).

BACKGROUND: Atherosclerosis is a common cardiovascular disease in parrots but the antemortem diagnosis is challenging. In human medicine, computed tomography angiography (CTA) has been used widely for the diagnosis of atherosclerosis. By adjusting the injection rate and total dose of contrast medium, the image quality can be improved. To test the effects of different injection conditions on the image quality of major arteries, 10 African grey parrots (Psittacus erithacus) were used. Three injection rates (0.3, 0.4, 0.5 mL/s) and three doses (740, 370, 222 mg of iodine/bird) were tested while the other variables of the studies were fixed. RESULT: A higher injection dose led to a significantly higher attenuation, image noise and diameter, with a lower signal-to-noise ratio and contrast-to-noise ratio of the six major arteries. The 370 mg of iodine/bird group showed significantly better subjective image quality. Furthermore, with increasing injection rates, the prevalence of heterogeneity decreased. However, we found an increased risk of injection failure for the 0.5 mL/s groups. CONCLUSION: We recommend a combination of 370 mg of iodine/bird with 0.4 mL/s for clinical use to achieve better image quality for CTA.

Comparative pathology of the nasal epithelium in K18-hACE2 Tg mice, hACE2 Tg mice, and hamsters infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes severe viral pneumonia and is associated with a high fatality rate. A substantial proportion of patients infected by SARS-CoV-2 suffer from mild hyposmia to complete loss of olfactory function, resulting in anosmia. However, the pathogenesis of the olfactory dysfunction and comparative pathology of upper respiratory infections with SARS-CoV-2 are unknown. We describe the histopathological, immunohistochemical, and in situ hybridization findings from rodent models of SARS-CoV-2 infection. The main histopathological findings in the olfactory epithelia of K8-hACE2 Tg mice, hACE2 Tg mice, and hamsters were varying degrees of inflammatory lesions, including disordered arrangement, necrosis, exfoliation, and macrophage infiltration of the olfactory epithelia, and inflammatory exudation. On the basis of these observations, the nasal epithelia of these rodent models appeared to develop moderate, mild, and severe rhinitis, respectively. Correspondingly, SARS-CoV-2 viral RNA and antigen were mainly identified in the olfactory epithelia and lamina propria. Moreover, viral RNA was abundant in the cerebrum of K18-hACE2 Tg mice, including the olfactory bulb. The K8-hACE2 Tg mouse, hACE2 Tg mouse, and hamster models could be used to investigate the pathology of SARS-CoV-2 infection in the upper respiratory tract and central nervous system. These models could help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.

First report of Neofusicoccum parvum causing leaf spot disease on Macadamia integrifolia in China.

The macadamia industry is developing rapidly in China. A brown leaf spot disease was noted in six Macadamia integrifolia plantations in Lincang, Yunnan, in October 2021. Over 60% of trees sampled had brown leaf spot symptoms, among approx.15,000 trees planted in these areas. Lesions (3 to 5 mm dia.) were small round brown spots with yellow edges. Lesions on severely infected leaves were darker and larger, with irregular shape (8 to 10 mm long, 3 to 6 mm wide). About 10% of diseased leaves had lesions characterized by a shot hole surrounded by a yellow halo. Potential pathogens were isolated from four randomly-selected symptomatic leaves from each of the six plantations by cutting lesion edges into small pieces. The pieces were surface sterilized, placed onto water agar containing 100 ppm aureomycin and incubated for 5 days at 24°C in the dark. Subculturing microbial growth on potato dextrose agar produced single-hyphal isolates with white fluffy aerial mycelia that turned pale olivaceous gray after 4 to 5 days. In four randomly-selected cultures, conidia were single celled, hyaline, spindle shaped to oval, and measured 10.9 to 16.3 µm long and 4.0 to 6.2 µm wide (n = 50). These characteristics matched those of Neofusicoccum parvum (Pavlic et al. 2009). Isolate LC013 was randomly selected as a representative individual for molecular identification. Internal transcribed spacer (ITS; ITS1/ITS4 primers; White et al. 1990), beta-tubulin gene (tub2; BT2A/BT2B primers; Glass and Donaldson 1995) and translation elongation factor 1-alpha gene (tef1-α; EF1-728F/EF2 primers; Carbone and Kohn 1999; O'Donnell et al. 1998) regions were PCR amplified from genomic DNA. Sequences of the products were used to BLAST probe the type specimen nucleotide sequences in GenBank. The LC013 sequences (GenBank accessions OM392021 (ITS); OM453641 (tub2); OM567656 (tef1-α)) had >99% sequence identity with analogous sequences from the type specimen of N. parvum CBS 138823 (accessions AY236943 (ITS); AY236917 (tub2); AY236888 (tef1-α)). Isolate LC013 was sister to N. parvum type strain in a maximum-likelihood (ML) tree constructed from analogous concatenated ITS, tef1-α, and tub2 sequences of 27 species that are phylogenetically closely-related to LC013 based on the ITS single locus ML tree. Koch's postulates were tested twice with two isolates by wounding leaves of four 14-month-old M. integrifolia seedlings with a sterile needle and placing a 5-mm-diameter agar plug containing N. parvum on the wound site. PDA plugs alone were used as uninoculated controls. Leaves were covered with sealed bags to maintain >90% humidity for 24 hours. All plants were kept in the same glasshouse under natural conditions. Leaves of inoculated plants began to discolor at 5 days post-inoculation (dpi). Brown spot symptoms were observed at 9 dpi. Control plants were symptomless. N. parvum was re-isolated from leaf lesions of the infected plants, but not from control plants, thus fulfilling Koch's postulates. N. parvum is an aggressive pathogen that causes severe disease on important tree and woody species, including M. integrifolia (Liddle et al. 2019). In China, it has been reported to cause leaf spot disease on 26 plant species (Farr and Rossman 2022), but this is the first report of N. parvum causing leaf spot disease on M. integrifolia. Further investigation is required to estimate the importance of this pathogen to the macadamia industry in China.

Extracorporeal Shock Wave Therapy Provides Limited Therapeutic Effects on Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis.

Night wrist splinting has been a conservative treatment for carpal tunnel syndrome. The addition of extracorporeal shock wave therapy provides an alternative treatment. However, strong evidence on the clinical effectiveness of extracorporeal shock wave therapy for carpal tunnel syndrome is still lacking. This study aimed to investigate the effectiveness and safety of extracorporeal shock wave therapy compared with treatments of night wrist splints alone for patients with carpal tunnel syndrome. In this systematic review and meta-analysis, no limitation criteria were used for study selection. All available articles that compare the effectiveness between extracorporeal shock wave therapy combined with night wrist splint and night wrist splint alone for treating carpal tunnel syndrome published up to 20 January 2022 were identified from the databases of PubMed, Embase, and Cochrane Central Register of Controlled Trials Central. The primary outcomes were a standard mean difference with a 95% confidence interval on the improvement of symptom severity and functional impairment between the two groups. In an attempt to analyze trends over time in studies that report repeated measurements, an all time-points meta-analysis (ATM) was undertaken. Seven randomized controlled trials with a total of 376 participants were included in this study. Significant improvements in functional impairment and symptom remission were only observed in the extracorporeal shock wave group at four weeks post-treatment. Extracorporeal shock wave therapy did not demonstrate superior efficacy compared to treatment with night wrist splint alone at 8-10 and 12-14 weeks post-treatment, or through the ATM approach. In conclusion, the therapeutic effect of extracorporeal shock wave therapy is transient and mostly nonsignificant compared with using night wrist splint alone. No serious side effects were reported in all included studies. Other conservative treatments to ameliorate carpal tunnel syndrome symptoms are warranted.

Inverse Relationship between Mean Corpuscular Volume and T-Score in Chronic Dialysis Patients.

Background and Objectives: Osteoporosis and anemia are prevalent among chronic kidney disease stage 5D (CKD stage 5D) patients. Osteoblasts are known as the niche cells of hematopoietic stem cells (HSCs) and stimulate HSCs to form blood-cell lineages within bone marrow microenvironments. We hypothesized that an inverse correlation may exist between mean corpuscular volume (MCV), a surrogate for ineffective hematopoiesis, and bone mineral density (BMD) in the CKD stage 5D population. Materials and Methods: This is a cross-sectional designed cohort study evaluating CKD stage 5D patients who have received dialysis therapy for over three months. Baseline clinical characteristics and laboratory data were prospectively collected. The dual-energy X-ray absorptiometry (DXA) method was used to measure BMD at five sites, which were bilateral femoral neck, total hip, and lumbar spine 1-4. The Pearson correlation test was initially adopted, and a multivariate linear regression model was further applied for potential confounder adjustments. Results: From September 2020 to January 2021, a total of 123 CKD stage 5D patients were enrolled. The Pearson correlation test revealed a significant inverse association between MCV and BMD at bilateral femoral neck and lumbar spine. The lowest T-score of the five body sites was determined as the recorded T-score. After adjustments for several potential confounding factors, the multivariate linear regression model found consistent negative associations between T-score and MCV. Conclusions: The present study found significant inverse correlations between MCV and BMD at specific body locations in patients on dialysis. A decreased T-score was also found to be associated with macrocytosis after adjustments for confounding variables. However, direct evidence for the causative etiology was lacking.

Multipronged Programmatic Strategy for Preventing Secondary Fracture and Facilitating Functional Recovery in Older Patients after Hip Fractures: Our Experience in Taipei Municipal Wanfang Hospital.

Background and Objectives: The study assessed the effectiveness of a fracture liaison service (FLS) after 1 year of implementation in improving the outcomes of hip fracture surgery in older adult patients at Taipei Municipal Wanfang Hospital. Materials and Methods: The Wanfang hospital's FLS program was implemented using a multipronged programmatic strategy. The aims were to encourage the screening and treatment of osteoporosis and sarcopenia, to take a stratified care approach for patients with a high risk of poor postoperative outcomes, and to offer home visits for the assessment of environmental hazards of falling, and to improve the patient's adherence to osteoporosis treatment. The clinical data of 117 and 110 patients before and after FLS commencement, respectively, were collected from a local hip fracture registry; the data were analyzed to determine the outcomes 1 year after hip fracture surgery in terms of refracture, mortality, and activities of daily living. Results: The implementation of our FLS significantly increased the osteoporosis treatment rate after hip fracture surgery from 22.8% to 72.3%, significantly decreased the 1-year refracture rate from 11.8% to 4.9%, non-significantly decreased 1-year mortality from 17.9% to 11.8%, and improved functional outcomes 1 year after hip fracture surgery. Conclusions: Implementation of our FLS using the multipronged programmatic strategy effectively improved the outcomes and care quality after hip fracture surgery in the older adult population, offering a successful example as a valuable reference for establishing FLS to improve the outcomes in vulnerable older adults.

Relationship Between Arterial and Intraosseous Pressure in African Grey Parrots (Psittacus erithacus).

The aim of this study was to determine the relationship between arterial pressure and intraosseous (IO) pressure obtained by conventional IO needle in African grey parrots (Psittacus erithacus). Twelve healthy African grey parrots with mean body weight 465.25 g were anesthetized in an induction chamber with 5% isoflurane and 100% oxygen, followed by intubation and connection to a pressure-limited intermittent-flow ventilator. A 24-gauge catheter was placed into the deep radial artery in one wing and a 22-gauge needle was placed into the distal ulnar medullary cavity in the contralateral wing. Both cannulas were connected to a 9-cm noncompliant tube and then linked to a disposable pressure sensor. Pressures and waveforms from both cannulas were recorded for 10 minutes while isoflurane was maintained at 3%. The results showed that the arterial pressure values were normally distributed (P < .05), whereas the IO pressure values were not (P > .05). Arterial and IO pressure were not correlated (P > 0.05), but IO pressure and heart rate were positively correlated (Spearman's rank correlation coefficient, 0.58; P < .05). Multiple characteristics of the IO waveforms were observed, including distinguishable continuous waveforms (n = 8), a single wave crest (n = 4), respiratory variation (n = 7), and a dicrotic notch (n = 3), and IO waveforms were appearing at a similar or delayed point relative to the related arterial waveforms (n = 8). Although IO pressure was not correlated with arterial pressure in the African grey parrots under the study conditions, the positive correlation between IO pressure and heart rate and the IO waveform characteristics suggest that the inflow arterioles likely account for the retained arterial waveform radiating into the IO space. These findings are consistent with those from all previously tested mammals. Therefore, insights into potential future improvements of the measuring techniques and protocols can be reached by thoroughly reviewing the current knowledge on IO pressure in mammals.

[Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain]. / è¶ å£°å¼•å¯¼å† é•œä¸‹é€†è¡Œé˜‘å°¾ç‚Žæ²»ç–—æœ¯åœ¨é˜‘å°¾ç›¸å ³æ ¢æ€§è ¹ç—›æ‚£å„¿ä¸­çš„åº”ç”¨ä»·å€¼.

OBJECTIVES: To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain. METHODS: A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate. RESULTS: Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%). CONCLUSIONS: Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.