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Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA ≥4:6)-matched UCB units. In HK, four patients received four 4-μl injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-μl injections (3.2 million cells). The eight patients were an average of 13 years after C5-T10 SCI. Magnetic resonance diffusion tensor imaging of five patients showed white matter gaps at the injury site before treatment. Two patients had fiber bundles growing across the injury site by 12 months, and the rest had narrower white matter gaps. Motor, walking index of SCI (WISCI), and spinal cord independence measure (SCIM) scores did not change. In KM, five groups of four patients received four 4-μl (1.6 million cells), 8-μl (3.2 million cells), 16-μl injections (6.4 million cells), 6.4 million cells plus 30 mg/kg methylprednisolone (MP), or 6.4 million cells plus MP and a 6-week course of oral lithium carbonate (750 mg/day). KM patients averaged 7 years after C3-T11 SCI and received 3–6 months of intensive locomotor training. Before surgery, only two patients walked 10 m with assistance and did not need assistance for bladder or bowel management before surgery. The rest could not walk or do their bladder and bowel management without assistance. At about a year (41–87 weeks), WISCI and SCIM scores improved: 15/20 patients walked 10 m (p = 0.001) and 12/20 did not need assistance for bladder management (p = 0.001) or bowel management (p = 0.002). Five patients converted from complete to incomplete (two sensory, three motor; p = 0.038) SCI. We conclude that UCB-MNC transplants and locomotor training improved WISCI and SCIM scores. We propose further clinical trials.

عصر الأزتك : أمة الشمس والأرض-ديفيد كاراسكو، سكوت سيشونز يركز هذا الكتاب على الحياة اليومية للأزتك، خاصة أولئك الذين أقاموا داخل جزيرة تينوتشيتلان وحولها. كما يقدم لنا الكتاب فكرة واضحة عن الوجه الإنساني لهذا الشعب، الذي تساءل شعراؤه عن مصاير قلوبهم وجهد مواطنوه لإقامة صداقات دائمة ونظر آباؤه وأمهاته إلى أبنائهم بوصفهم (عقودا ثمينة) كما حيا أبناؤه الشمس عند شروقها وقتلوا أثناء الحروب وهم على يقين بأنهم، رغم دفنهم في باطن الأرض، أو نثر رماد أجسادهم فوق تراب الوطن، فإنهم سيخلدون في بيت الإله الشمس. ويسعى هذا الكتاب لعقد مقاربة جديدة للعلاقات المركبة بين الممارسات الثقافية والنظام الاجتماعي والأساطير والرموز الدينية.

Background Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally, and a number of treatment and preventive strategies have been tried for years. Lifestyle modification programs have been widely implemented as a primary prevention strategy to reduce the burden of CVDs. However, their effectiveness in patients with established CVD in monitoring modifiable risk factors is controversial and requires further investigation. Methods A comprehensive search was conducted in PubMed, Cochrane, Science Direct, and LILACS without date and language restrictions. All randomized controlled trials (RCT) comparing the effectiveness of lifestyle modification and/ or optimization of drug therapies among patients with established cardiovascular disease were included. The primary outcomes were changes in systolic blood pressure and low-density lipoprotein cholesterol. Secondary outcomes included changes in total cholesterol, diastolic blood pressure, and medication adherence. Meta-analysis results were reported as standardized mean difference (SMD) or risk ratio (RR) and 95% confidence intervals (CI). Sub-analyses examined programs that included both lifestyle modification and drug optimization or type of intervention alone if a minimum of three trials were identified. The quality of evidence was evaluated using GRADE and trial sequential analyses. Results Sixteen trials including 4450 participants were included in testing programs focused on both lifestyle modification and drug optimisation (seven RCTs) and lifestyle modification alone (nine RCTs). Overall the programs significantly reduced systolic blood pressure (SMD =  − 0.30, 95% CI − 0.43 to − 0.17, P  < 0.001), diastolic blood pressure (SMD =  − 0.18, 95% CI − 0.28 to − 0.08 P  < 0.001), total cholesterol (SMD =  − 0.28, 95% CI − 0.49 to − 0.07, P  = 0.009); however, the quality of evidence was rated as low. Conclusion Lifestyle modification and medication optimization interventions had a significant effect on monitoring blood pressure and serum cholesterol; however, the provision of the firm conclusion is less optimal with current evidence as the quality of evidence was low. Systematic review registration The systematic review and meta-analysis protocol was registered in PROSPERO CRD42024523078.

Background Adequate facemask ventilation during induction of anaesthesia is a key aspect of patient safety. Difficulties can therefore be life-threatening for the patient. Case presentation The case presented here illustrates a rare cause of an orbital fistula that led to a serious problem during facemask ventilation and demonstrates why team communication is so important. Conclusions Preparatory errors in patient assessment and anaesthetic preparation were identified as sources of error.

The unspliced HIV-1 full-length RNA (HIV-1 RNA) is packaged into virions as the genome and is translated to generate viral structural proteins and enzymes. To serve these functions, HIV-1 RNA must be exported from the nucleus to the cytoplasm. It was recently suggested that export pathways used by HIV-1 RNA could affect its cytoplasmic transport mechanisms and distribution. In the current report, we examined the HIV-1 RNA transport mechanism by following the movement of individual RNAs and identifying the distribution of RNA using in situ hybridization. Our results showed that whether exported by the CRM1 or NXF1 pathway, HIV-1 RNAs mainly use diffusion for cytoplasmic travel. Furthermore, HIV-1 RNAs exported using the CRM1 or NXF1 pathway are well mixed in the cytoplasm and do not display export pathway-specific clustering near centrosomes. Thus, the export pathways used by HIV-1 RNAs do not alter the cytoplasmic transport mechanisms or distribution. HIV-1 full-length RNA (referred to as HIV-1 RNA here) serves as the viral genome in virions and as a template for Gag/Gag-Pol translation. We previously showed that HIV-1 RNA, which is exported via the CRM1 pathway, travels in the cytoplasm mainly through diffusion. A recent report suggested that the export pathway used by retroviral RNA could affect its cytoplasmic transport mechanism and localization. HIV-1 RNA export is directed by the viral protein Rev and the cis -acting element, Rev response element (RRE). When Rev/RRE is replaced with the constitutive transport element (CTE) from Mason-Pfizer monkey virus (MPMV), HIV-1 RNA is exported through the NXF1 pathway. To determine the effects of the export pathway on HIV-1 RNA, we tracked individual RNAs and found that the vast majority of cytoplasmic HIV-1 RNAs travel by diffusion regardless of the export pathway. However, CTE-containing HIV-1 RNA diffuses at a rate slower than that of RRE-containing HIV-1 RNA. Using in situ hybridization, we analyzed the subcellular localizations of HIV-1 RNAs in cells expressing a CTE-containing and an RRE-containing provirus. We found that these two types of HIV-1 RNAs have similar subcellular distributions. HIV-1 RNA exported through the NXF1 pathway was suggested to cluster near centrosomes. To investigate this possibility, we measured the distances between individual RNAs to the centrosomes and found that HIV-1 RNAs exported through different pathways do not exhibit significantly different distances to centrosomes. Therefore, HIV-1 RNAs exported through CRM1 and NXF1 pathways use the same RNA transport mechanism and exhibit similar cytoplasmic distributions. IMPORTANCE The unspliced HIV-1 full-length RNA (HIV-1 RNA) is packaged into virions as the genome and is translated to generate viral structural proteins and enzymes. To serve these functions, HIV-1 RNA must be exported from the nucleus to the cytoplasm. It was recently suggested that export pathways used by HIV-1 RNA could affect its cytoplasmic transport mechanisms and distribution. In the current report, we examined the HIV-1 RNA transport mechanism by following the movement of individual RNAs and identifying the distribution of RNA using in situ hybridization. Our results showed that whether exported by the CRM1 or NXF1 pathway, HIV-1 RNAs mainly use diffusion for cytoplasmic travel. Furthermore, HIV-1 RNAs exported using the CRM1 or NXF1 pathway are well mixed in the cytoplasm and do not display export pathway-specific clustering near centrosomes. Thus, the export pathways used by HIV-1 RNAs do not alter the cytoplasmic transport mechanisms or distribution.

Background Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration. Methods We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m 2 ). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV. Results With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS ( p  = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p  = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p  = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p  = 0.003) and PFS (3.6 vs. 8.4 months, p <0.0001). DXM did not reduce OS in patients who received TMZ and BEV concurrently with RT (22.9 vs 22.8 months, p  = 0.4818). On multivariable analysis, DXM use predicted an unfavorable OS hazard ratio (HR) = 1.72, p  = 0.045). Conclusions Our results with TMZ, BEV, and RT are similar to previous studies in terms of PFS and OS. DXM use during RT with concurrent TMZ correlated with reduced OS and PFS unless BEV was administered.

This article presents a musical interface that enables the sonification of data from the human microbiota, the trillions of microorganisms that inhabit the human body, into sound and music. The project is concerned with public engagement in science, particularly the life sciences, and developing cultivation technologies that take advantage of the ubiquitous and accessible nature of the human microbiota. In this article we examine the collaboration between team members proficient in musical composition and those with expertise in biology, sonification, and data visualization, producing an individualized piece of music designed to capture basic biological data and user attention. Although this system, called Biota Beats, sonifies ubiquitous data for educational science projects, it also establishes a connection between individuals and their bodies and between a community and its context through interactive music experiences, while attempting to make the science of the human microbiome more accessible. The science behind standardizing sonified data for scientific, human analysis is still in development (in comparison to charts, graphs, spectrograms, or other types of data visualization). So a more artistic approach, using the framework of musical genres and their associated themes and motifs, is a convenient and previously established way to capitalize on how people naturally perceive sound. Further, to forge a creative connection between the human microbiota and the music genre, a philosophical shift is necessary, that of viewing the human body and the digital audio workstation as ubiquitous computers.

Although combination antiretroviral therapy (ART) blocks HIV replication, it is not curative because infected CD4+ T cells that carry intact, infectious proviruses persist. Understanding the behavior of clones of infected T cells is important for understanding the stability of the reservoir; however, the stabilities of clones of infected T cells in persons on long-term ART are not well defined. We determined the relative stabilities of clones of infected and uninfected CD4+ T cells over time intervals of one to four years in three individuals who had been on ART for 9–19 years. The largest clones of uninfected T cells were larger than the largest clones of infected T cells. Clones of infected CD4+ T cells were more stable than clones of uninfected CD4+ T cells of a similar size. Individual clones of CD4+ T cells carrying intact, infectious proviruses can expand, contract, or remain stable over time.

Patients with recurrent glioblastoma (GBM) have limited treatment options. This study determined whether patients with recurrent GBM treated with initial radiation/temozolomide (TMZ) and reirradiation using fractionated stereotactic radiotherapy (FSRT) had improved outcomes. We identified 95 patients with recurrent GBM, 50 of whom underwent FSRT at recurrence and 45 who had systemic treatment only (control). The median total FSRT dose at the time of GBM recurrence was 30 Gy in five fractions of the gadolinium-enhanced tumor only. With a median follow-up of 18 months, the progression-free survival (PFS) and overall survival (OS) following initial GBM diagnosis were longer in the reirradiation group compared to the control group (13.5 vs. 7.5 months [p=0.001] and 24.6 vs. 12.6 months [p<0.001], respectively). For patients who underwent reirradiation, the median time interval between the end of the initial radiation and reirradiation was 15.2 months. The median OS after GBM recurrence was longer in the reirradiation group versus the control group (9.9 vs. 3.5 months [p<0.001]), with a one-year OS survival rate of 22%. The hazard ratio for death of patients in the reirradiation group was 0.31 [0.19-0.50]. The reirradiation group had a higher percentage of patients who received bevacizumab (BEV, 62.0% vs. 28.9%, p=0.002) and a lower percentage of patients whose TMZ was discontinued due to toxicity (8.0% vs. 28.9%, p=0.017) compared to the control group. Reirradiation utilizing FSRT was associated with improved PFS and OS after GBM recurrence compared to the control group who did not receive additional irradiation.