The incidence of brain trauma caused by road injuries: Results from the Global Burden of Disease Study 2019.

BACKGROUND: Road collisions are a significant source of traumatic brain injury (TBI). We aimed to determine the pattern of road injury related TBI (RI-TBI) incidence, as well as its temporal trends. METHODS: We collected detailed information on RI-TBI between 1990 and 2019, derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPCs) of RI-TBI age standardized incidence rate (ASIR), by sex, region, and cause of road injuries, were assessed to quantify the temporal trends of RI-TBI burden. RESULTS: Globally, incident cases of RI-TBI increased 68.1% from 6,900,000 in 1990 to 11,600,000 in 2019. The overall ASIR increased by an average of 0.43% (95% CI 0.30%-0.56%) per year during this period. The ASIR of RI-TBI due to cyclist, motorcyclist and other road injuries increased between 1990 and 2019; the corresponding EAPCs were 0.56 (95% CI 0.37-0.75), 1.60 (95% CI 1.35-1.86), and 0.75 (95% CI 0.59-0.91), respectively. In contrast, the ASIR of RI-TBI due to motor vehicle and pedestrian decreased with an EAPC of -0.12 and -0.14 respectively. The changing pattern for RI-TBI was heterogeneous across countries and regions. The most pronounced increases were observed in Mexico (EAPC = 3.74), followed by China (EAPC = 2.45) and Lesotho (EAPC = 1.91). CONCLUSIONS: RI-TBI remains a major public health concern worldwide, although road safety legislations have contributed to the decreasing incidence in some countries. We found an unfavorable trend in several countries with a relatively low socio-demographic index, suggesting that much more targeted and specific approaches should be adopted in these areas to forestall the increase in RI-TBI.

Diagnostic performance of VEGF-D for lymphangioleiomyomatosis: a meta-analysis.

OBJECTIVE: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. METHODS: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. RESULTS: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. CONCLUSIONS: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

Diagnostic performance of VEGF-D for lymphangioleiomyomatosis: a meta-analysis / Desempenho diagnóstico do VEGF-D para linfangioleiomiomatose: meta-análise

ABSTRACT Objective: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

RESUMO Objetivo: O VEGF-D é um potencial biomarcador para linfangioleiomiomatose (LAM); entretanto, seu desempenho diagnóstico ainda não foi sistematicamente estudado. Métodos: Foram realizadas buscas nos bancos de dados PubMed, EMBASE, Scopus, Web of Science e Cochrane Library para identificar estudos primários sobre o VEGF-D com relação ao diagnóstico de LAM. A qualidade dos estudos foi avaliada por meio da ferramenta Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). As estimativas sumárias de acurácia diagnóstica foram combinadas utilizando um modelo bivariado de efeitos aleatórios. Análises de subgrupo e de sensibilidade foram realizadas para explorar possíveis heterogeneidades. O sistema Grading of Recommendations Assessment, Development, and Evaluation (GRADE) foi aplicado para avaliar a qualidade das evidências e indicar a força das recomendações. Resultados: Dez estudos envolvendo 945 pacientes eram de alto risco em qualidade, segundo a ferramenta QUADAS-2. Os parâmetros diagnósticos combinados foram indicados da seguinte forma: sensibilidade = 0,82 (IC95%: 0,71-0,90); especificidade = 0,98 (IC95%: 0,94-0,99); e OR diagnóstica = 197 (IC95%: 66-587). A ASC da análise summary ROC foi de 0,98. As análises de subgrupo e de sensibilidade revelaram que o desempenho global não foi substancialmente afetado pela composição do grupo controle, valor de corte pré-especificado, país de origem ou diferentes valores de corte (p > 0,05 para todos). Uma forte recomendação para a dosagem de VEGF-D sérico para auxiliar no diagnóstico de LAM foi feita de acordo com o sistema GRADE. Conclusões: O VEGF-D parece ter grandes implicações potenciais para o diagnóstico de LAM na prática clínica em virtude da excelente especificidade e sensibilidade subótima.

Allocation of pharmaceutical resources in maternal and child healthcare institutions during the COVID-19 pandemic.

Since the outbreak of a cluster of patients with pneumonia of unknown cause in Wuhan, Hubei Province, China, in December 2019, the disease was later officially named coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), quickly spreading globally. Pregnant women and children are particularly vulnerable during disasters and emergencies. Comprehensive and applicable emergency preparedness and response are definitely important methods to prevent and contain the COVID-19 pandemic. The rational allocation of pharmaceutical resources plays an important role in the medical emergency plan. This paper aimed to share experiences for the allocation of pharmaceutical resources in hospitals focusing primarily on women and children during the COVID-19 pandemic.

Partial replacement of inorganic phosphorus (P) by organic manure reshapes phosphate mobilizing bacterial community and promotes P bioavailability in a paddy soil.

The optimization of more sustainable fertilization practice to relieve phosphorus (P) resource scarcity and increase P fertilizer utilization, a better understanding of the regulatory roles of microbes in P mobilization is urgently required to reduce P input. The genes phoD and pqqC are responsible for regulating organic and inorganic P mobilization, respectively. Using high-throughput sequencing, the corresponding bacterial communities harbored by these genes were determined. We conducted a 4-year rice-rice-crop rotation to investigate the responses of phoD- and pqqC-harboring bacterial communities to the partial replacement of inorganic P fertilizer by organic manure with reduced P input. The results showed that a combination of organic and inorganic fertilization maintained high rice yield, and also produced a more complex and stable phosphate mobilizing bacterial community, which contributed to phosphatase activities more than their gene abundances in the model analysis. Compared with the conventional mineral fertilization, organic-inorganic fertilization with the reduced P input slightly increased pqqC gene abundance while significantly enhanced the abundance of phoD-harboring bacteria, especially the genera Bradyrhizobium and Methylobacterium known as potential organic P mineralizers which can maintain high rice production. Moreover, the increased pH was the most impactful factor for the phoD- and pqqC-harboring bacterial communities, by promoting microbial P turnover and greatly increasing bioavailable P pools (H2O-Pi and NaHCO3-Pi, NaOH-Pi) in this P-deficient paddy soil. Hence, our study demonstrated that the partial replacement of mineral P with organic manure could reshape the inorganic phosphate solubilizing and alkaline-phosphomonoesterase encoding bacterial communities towards more resilient and effective to the high P utilization and productivity over intense cultivation, providing insights into the potential of soil microbes in the efficient management of agricultural P fertilization.

Allocation of pharmaceutical resources in maternal and child healthcare institutions during the COVID-19 pandemic

SUMMARY Since the outbreak of a cluster of patients with pneumonia of unknown cause in Wuhan, Hubei Province, China, in December 2019, the disease was later officially named coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), quickly spreading globally. Pregnant women and children are particularly vulnerable during disasters and emergencies. Comprehensive and applicable emergency preparedness and response are definitely important methods to prevent and contain the COVID-19 pandemic. The rational allocation of pharmaceutical resources plays an important role in the medical emergency plan. This paper aimed to share experiences for the allocation of pharmaceutical resources in hospitals focusing primarily on women and children during the COVID-19 pandemic.

RESUMO Desde o aparecimento de um aglomerado de doentes com pneumonia de causa desconhecida em Wuhan, província de Hubei, China, em dezembro de 2019, a doença foi mais tarde oficialmente nomeada doença do coronavírus 2019 (Covid-19), causada pelo novo vírus da síndrome respiratória aguda grave coronavírus (Sars-CoV-2), que rapidamente se espalhou em nível mundial. As mulheres grávidas e as crianças são particularmente vulneráveis durante catástrofes e emergâncias. A preparação e a resposta de emergência abrangentes e aplicáveis são métodos definitivamente importantes para prevenir e conter a pandemia de Covid-19. A alocação racional dos recursos farmacêuticos desempenha um papel importante no plano de emergência médica. Este documento objetivou compartilhar experiências para a alocação de recursos farmacêuticos em hospitais focando principalmente mulheres e crianças durante a pandemia de Covid-19.

An anterior neurovascular interval approach to coronal shear fractures of the distal humerus: a prospective clinical study with short- to mid-term follow-up.

OBJECT: To explore the treatment effect of the anterior medial neurovascular interval approach to coronal shear fractures of the distal humerus. METHODS: This prospective study included two female patients who were 30-64 years old, with a mean age of 47 years. Fractures were caused by falling from a bicycle. The time between the injury and operation was 1-2 days, with a mean time interval of 1.5 days. Two patients with coronal shear fracture of the distal humerus were treated with open reduction and internal fixation using anterior neurovascular interval approach. RESULTS: There were no intraoperative and postoperative neurological and vascular complications or infections, and the fracture was united. At 12 months after the surgery, the patient returned to work without pain, and with a normal range of motion for elbow and forearm rotation. The X-rays revealed excellent fracture union, no signs of heterotopic ossification, and no traumatic arthritis. According to Mayo's evaluation standards for elbow function, a score of 100 is excellent. CONCLUSIONS: The application of the anterior neurovascular interval approach of the elbow in the treatment of shear fracture of the articular surface of the distal humerus, particularly the trochlea of the humerus, can reduce the stripping of the soft tissue.

An anterior neurovascular interval approach to coronal shear fractures of the distal humerus: a prospective clinical study with short- to mid-term follow-up

SUMMARY OBJECT: To explore the treatment effect of the anterior medial neurovascular interval approach to coronal shear fractures of the distal humerus. METHODS: This prospective study included two female patients who were 30-64 years old, with a mean age of 47 years. Fractures were caused by falling from a bicycle. The time between the injury and operation was 1-2 days, with a mean time interval of 1.5 days. Two patients with coronal shear fracture of the distal humerus were treated with open reduction and internal fixation using anterior neurovascular interval approach. RESULTS: There were no intraoperative and postoperative neurological and vascular complications or infections, and the fracture was united. At 12 months after the surgery, the patient returned to work without pain, and with a normal range of motion for elbow and forearm rotation. The X-rays revealed excellent fracture union, no signs of heterotopic ossification, and no traumatic arthritis. According to Mayo's evaluation standards for elbow function, a score of 100 is excellent. CONCLUSIONS: The application of the anterior neurovascular interval approach of the elbow in the treatment of shear fracture of the articular surface of the distal humerus, particularly the trochlea of the humerus, can reduce the stripping of the soft tissue.

RESUMO OBJETIVO: Explorar o efeito do tratamento com uma abordagem anterior do intervalo neurovascular médio para fraturas de cisalhamento coronal da porção distal do úmero. METODOLOGIA: Este estudo prospectivo incluiu duas pacientes do sexo feminino de 30-64 anos de idade, com idade média de 47 anos. As fraturas foram causadas por quedas de bicicleta. O tempo entre a lesão e a operação foi de 1-2 dias, com um intervalo de tempo médio de 1,5 dias. Duas pacientes com cisalhamento coronal da porção distal do úmero foram tratadas com redução aberta e fixação interna utilizando a abordagem anterior do intervalo neurovascular. RESULTADOS: Não houve complicações neurológicas e vasculares intra e pós-operatórias, nem complicações ou infecções, e a fratura foi unida. Após 12 meses da cirurgia, as pacientes retornaram ao trabalho sem dor e com uma amplitude normal de movimento de rotação do antebraço e cotovelo. Os raios-X revelaram excelente união das fraturas, sem sinais de ossificação heterotópica e sem artrite traumática. De acordo com as diretrizes da clínica Mayo para avaliação da função do cotovelo, uma pontuação de 100 é considerada excelente. CONCLUSÃO: A aplicação da abordagem anterior do intervalo neurovascular do cotovelo no tratamento de uma fratura de cisalhamento da superfície articular da porção distal do úmero, especificamente da tróclea do úmero, pode reduzir o desgaste do tecido mole.

Standard method for detecting Bombyx mori nucleopolyhedrovirus disease-resistant silkworm varieties

ABSTRACT Bombyx mori nucleopolyhedrovirus (BmNPV) disease is one of the most serious silkworm diseases, and it has caused great economic losses to the sericulture industry. So far, the disease has not been controlled effectively by therapeutic agents. Breeding resistant silkworm varieties breeding may be an effective way to improve resistance to BmNPV and reduce economic losses. A precise resistance-detection method will help to accelerate the breeding process. For this purpose, here we described the individual inoculation method (IIM). Details of the IIM include pathogen BmNPV preparation, mulberry leaf size, pathogen volume, rearing conditions, course of infection, and breeding conditions. Finally, a resistance comparison experiment was performed using the IIM and the traditional group inoculation method (GIM). The incidence of BmNPV infection and the within-group variance results showed that the IIM was more precise and reliable than the GIM.

Impulsivity, Rejection Sensitivity, and Reactions to Stressors in Borderline Personality Disorder.

This research investigated baseline impulsivity, rejection sensitivity, and reactions to stressors in individuals with borderline personality disorder compared to healthy individuals and those with avoidant personality disorder. The borderline group showed greater impulsivity than the avoidant and healthy groups both in a delay-discounting task with real monetary rewards and in self-reported reactions to stressors; moreover, these findings could not be explained by co-occurring substance use disorders. Distress reactions to stressors were equally elevated in both personality disorder groups (relative to the healthy group). The borderline and avoidant groups also reported more maladaptive reactions to a stressor of an interpersonal vs. non-interpersonal nature, whereas the healthy group did not. Finally, self-reported impulsive reactions to stressors were associated with baseline impulsivity in the delay-discounting task, and greater self-reported reactivity to interpersonal than non-interpersonal stressors was associated with rejection sensitivity. This research highlights distinct vulnerabilities contributing to impulsive behavior in borderline personality disorder.

Hyperhomocysteinemia potentiates hyperglycemia-induced inflammatory monocyte differentiation and atherosclerosis.

Hyperhomocysteinemia (HHcy) is associated with increased diabetic cardiovascular diseases. However, the role of HHcy in atherogenesis associated with hyperglycemia (HG) remains unknown. To examine the role and mechanisms by which HHcy accelerates HG-induced atherosclerosis, we established an atherosclerosis-susceptible HHcy and HG mouse model. HHcy was established in mice deficient in cystathionine ß-synthase (Cbs) in which the homocysteine (Hcy) level could be lowered by inducing transgenic human CBS (Tg-hCBS) using Zn supplementation. HG was induced by streptozotocin injection. Atherosclerosis was induced by crossing Tg-hCBS Cbs mice with apolipoprotein E-deficient (ApoE(-/-)) mice and feeding them a high-fat diet for 2 weeks. We demonstrated that HHcy and HG accelerated atherosclerosis and increased lesion monocytes (MCs) and macrophages (MØs) and further increased inflammatory MC and MØ levels in peripheral tissues. Furthermore, Hcy-lowering reversed circulating mononuclear cells, MC, and inflammatory MC and MC-derived MØ levels. In addition, inflammatory MC correlated positively with plasma Hcy levels and negatively with plasma s-adenosylmethionine-to-s-adenosylhomocysteine ratios. Finally, l-Hcy and d-glucose promoted inflammatory MC differentiation in primary mouse splenocytes, which was reversed by adenoviral DNA methyltransferase-1. HHcy and HG, individually and synergistically, accelerated atherosclerosis and inflammatory MC and MØ differentiation, at least in part, via DNA hypomethylation.

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.

We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.

Identification and expression analysis of four 14-3-3 genes during fruit ripening in banana (Musa acuminata L. AAA group, cv. Brazilian).

To investigate the regulation of 14-3-3 proteins in banana (Musa acuminata L. AAA group, cv. Brazilian) fruit postharvest ripening, four cDNAs encoding 14-3-3 proteins were isolated from banana and designated as Ma-14-3-3a, Ma-14-3-3c, Ma-14-3-3e, and Ma-14-3-3i, respectively. Amino acid sequence alignment showed that the four 14-3-3 proteins shared a highly conserved core structure and variable C-terminal as well as N-terminal regions with 14-3-3 proteins from other plant species. Phylogenetic analysis revealed that the four 14-3-3 genes belong to the non-ε groups. They were differentially and specifically expressed in various tissues. Real-time RT-PCR analysis indicated that these four genes function differentially during banana fruit postharvest ripening. Three genes, Ma-14-3-3a, Ma-14-3-3c, and Ma-14-3-3e, were significantly induced by exogenous ethylene treatment. However, gene function differed in naturally ripened fruits. Ethylene could induce Ma-14-3-3c expression during postharvest ripening, but expression patterns of Ma-14-3-3a and Ma-14-3-3e suggest that these two genes appear to be involved in regulating ethylene biosynthesis during fruit ripening. No obvious relationship emerged between Ma-14-3-3i expression in naturally ripened and 1-MCP (1-methylcyclopropene)-treated fruit groups during fruit ripening. These results indicate that the 14-3-3 proteins might be involved in various regulatory processes of banana fruit ripening. Further studies will mainly focus on revealing the detailed biological mechanisms of these four 14-3-3 genes in regulating banana fruit postharvest ripening.

Mexicanolides from the seeds of a Krishna mangrove, Xylocarpus moluccensis.

Two new mexicanolides, named xylomexicanolides A and B, were isolated from the seeds of an Indian mangrove, Xylocarpus moluccensis, together with four known limonoids, khayasin, angolensic acid methyl ester, khayasin T, and 2'S-methylbutanoylproceranolide. The structures of these limonoids were established on the basis of spectroscopic data. The (13)C-NMR data of khayasin were reported for the first time. Khayasin was found to exhibit marked insecticidal activity against the fifth instar larvae of Brontispa longissima (GESTRO) at a concentration of 10 mg/l.

Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction.

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg(-1) day(-1)) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.