Walking on Tightrope: The Challenging Role of Science Advice in Managing the COVID-19 Pandemic in the Philippines

Science advice is an exercise in funambulism. To effectively influence the grand spectacle of politics, science needs to constantly walk on a tightrope, as it carries the weight of objectivity on one hand and the complex, often subjective, demands of the government and public sector on the other. Lean too much on either side and it can easily lose either its credibility in the eyes of the public or its seat in the corridors of power. This struggle is no small feat given that scientists have to “muddle through”—to borrow the words of Charles Lindblom (1959)—a system that is highly bureaucratic and not easily malleable to scientific persuasions. This delicate balancing act is even more critical during major disasters such as the ongoing COVID-19 pandemic. The trail that SARS-COV-2 leaves behind has all the ingredients of a challenging crisis: its impacts are massive and unprecedented, it requires urgent action, and it comes with a good deal of uncertainty. While it is not exactly a black swan event, it is pretty much a major perturbation that makes a perfect ground for science to assert its authority as a provider and arbiter of scientific evidence

Acute physical exercise improves shifting in adolescents at school: evidence for a dopaminergic contribution

The executive function of shifting between mental sets demands cognitive flexibility. Based on evidence that physical exercise fostered cognition, we tested whether acute physical exercise can improve shifting in an unselected sample of adolescents. Genetic polymorphisms were analyzed to gain more insight into possibly contributing neurophysiological processes. We examined 297 students aged between 13 and 17 years in their schools. Physical exercise was manipulated by an intense incremental exercise condition using bicycle ergometers and a control condition which involved watching an infotainment cartoon while sitting calm. The order of conditions was counterbalanced between participants. Shifting was assessed by a switching task after both conditions. Acute intense physical exercise significantly improved shifting as indicated by reduced switch costs. Exercise-induced performance gains in switch costs were predicted by a single nucleotide polymorphism (SNP) targeting the Dopamine Transporter (DAT1/SLCA6A3) gene suggesting that the brain dopamine system contributed to the effect. The results demonstrate the potential of acute physical exercise to improve cognitive flexibility in adolescents. The field conditions of the present approach suggest applications in schools

Clinical significance of VEGF-A, -C and -D expression in esophageal malignancies

Vascular endothelial growth factors ( VEGF)- A, - C and - D are members of the proangiogenic VEGF family of glycoproteins. VEGF-A is known to be the most important angiogenic factor under physiological and pathological conditions, while VEGF-C and VEGF-D are implicated in the development and sprouting of lymphatic vessels, so called lymphangiogenesis. Local tumor progression, lymph node metastases and hematogenous tumor spread are important prognostic factors for esophageal carcinoma ( EC), one of the most lethal malignancies throughout the world. We found solid evidence in the literature that VEGF expression contributes to tumor angiogenesis, tumor progression and lymph node metastasis in esophageal squamous cell carcinoma ( SCC), and many authors could show a prognostic value for VEGF-assessment. In adenocarcinoma (AC) of the esophagus angiogenic properties are acquired in early stages, particularly in precancerous lesions like Barrett's dysplasia. However, VEGF expression fails to give prognostic information in AC of the esophagus. VEGF-C and VEGF-D were detected in SCC and dysplastic lesions, but not in normal mucosa of the esophagus. VEGF-C expression might be associated with lymphatic tumor invasion, lymph node metastases and advanced disease in esophageal SCC and AC. Therapeutic interference with VEGF signaling may prove to be a promising way of anti-angiogenic co-treatment in esophageal carcinoma. However, concrete clinical data are still pending

Assessing the impacts of solar electrification program in rural schools: Experiences from the field

Electricity drives development. It increases productivity, enables efficiency, and generally improves the overall quality of life. Its impact in various sectors cannot be overemphasized, particularly in the education sector. This article highlights the experiences of nine rural public schools in the Philippines as beneficiaries of a solar electrification program. It analyzes the impacts of access to electricity by looking at how the experience of the students changed, the innovations introduced in teaching, and the modifications made to administrative operations. The findings highlight that the more direct impact of electrification is the provision of a better environment for learning. It also highlights other positive externalities as well as unintended consequences of having access to electricity. The article argues that although electrification has helped expand the opportunities for other stakeholders to get involved in improving education in rural areas, social buy-in needs to be continually secured and reinforced as well as strategic collaboration to be established to leverage the limited resources of the schools together with the willingness of the community to provide additional support towards sustaining the program. Keywords: solar electrification; rural public schools; impacts; educatio

VEGF is upregulated by hypoxia-induced mitogenic factor via the PI-3K/Akt-NF-κB signaling pathway

BACKGROUND: Hypoxia-induced mitogenic factor (HIMF) is developmentally regulated and plays an important role in lung pathogenesis. We initially found that HIMF promotes vascular tubule formation in a matrigel plug model. In this study, we investigated the mechanisms which HIMF enhances expression of vascular endothelial growth factor (VEGF) in lung tissues and epithelial cells. METHODS: Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, VEGF expression was examined by immunohistochemical staining and Western blot. The promoter-luciferase reporter assay, RT-PCR, and Western blot were performed to examine the effects of HIMF on VEGF expression in mouse lung epithelial cell line MLE-12. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK and IκBα were examined by luciferase assay and Western blot, respectively. RESULTS: Intratracheal instillation of HIMF protein resulted in significant increase of VEGF, mainly localized to airway epithelial and alveolar type II cells. Deletion of NF-κB binding sites within VEGF promoter abolished HIMF-induced VEGF expression in MLE-12 cells, suggesting that activation of NF-κB is essential for VEGF upregulation induced by HIMF. Stimulation of lung epithelial cells by HIMF resulted in phosphorylation of IKK and IκBα, leading to activation of NF-κB. In addition, HIMF strongly induced Akt phosphorylation, and suppression of Akt activation by specific inhibitors and dominant negative mutants for PI-3K, and IKK or IκBα blocked HIMF-induced NF-κB activation and attenuated HIMF-induced VEGF production. CONCLUSION: These results suggest that HIMF enhances VEGF production in mouse lung epithelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis

Vascular Endothelial Growth Factor (VEGF) isoform expression and activity in human and murine lung injury

<p>Abstract</p> <p>Background</p> <p>The properties of vascular endothelial growth factor (VEGF) as a potent vascular permogen and mitogen have led to investigation of its potential role in lung injury. Alternate spliced VEGF transcript generates several isoforms with potentially differing functions. The purpose of this study was to determine VEGF isoform expression and source in normal and ARDS subjects and investigate the expression and regulation of VEGF isoforms by human alveolar type 2 (ATII) cells.</p> <p>Methods</p> <p>VEGF protein expression was assessed immunohistochemically in archival normal and ARDS human lung tissue. VEGF isoform mRNA expression was assessed in human and murine lung tissue. Purified ATII cells were cultured with proinflammatory cytokines prior to RNA extraction/cell supernatant sampling/proliferation assay.</p> <p>Measurements and Main Results</p> <p>VEGF was expressed on alveolar epithelium, vascular endothelium and alveolar macrophages in normal and ARDS human lung tissue. Increases in VEGF expression were detected in later ARDS in comparison to both normal subjects and early ARDS (p < 0.001). VEGF₁₂₁, VEGF₁₆₅and VEGF₁₈₉isoform mRNA expression increased in later ARDS (p < 0.05). The ratio of soluble to cell-associated isoforms was lower in early ARDS than normal subjects and later ARDS and also in murine lung injury. ATII cells constitutionally produced VEGF₁₆₅and VEGF₁₂₁protein which was increased by LPS (p < 0.05). VEGF₁₆₅upregulated ATII cell proliferation (p < 0.001) that was inhibited by soluble VEGF receptor 1 (<it>sflt</it>) (p < 0.05).</p> <p>Conclusion</p> <p>These data demonstrate that changes in VEGF isoform expression occur in ARDS which may be related to their production by and mitogenic effect on ATII cells; with potentially significant clinical consequences.</p

IL-17A Expression Is Localised to Both Mononuclear and Polymorphonuclear Synovial Cell Infiltrates

This study examines the expression of IL-17A-secreting cells within the inflamed synovium and the relationship to in vivo joint hypoxia measurements.IL-17A expression was quantified in synovial tissue (ST), serum and synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and serum levels were measured by MSD-plex assays. Dual immunofluorescence for IL-17A was quantified in ST CD15+ cells (neutrophils), Tryptase+ (mast cells) and CD4+ (T cells). Synovial tissue oxygen (tpO(2)) levels were measured under direct visualisation at arthroscopy. Synovial infiltration was assessed using immunohistochemistry for cell specific markers. Peripheral blood mononuclear and polymorphonuclear cells were isolated and exposed to normoxic or 3% hypoxic conditions. IL-17A and IL-6 were quantified as above in culture supernatants.IL-17A expression was localised to mononuclear and polymorphonuclear (PMN) cells in inflamed ST. Dual immunoflourescent staining co-localised IL-17A expression with CD15+ neutrophils Tryptase+ mast cells and CD4+T cells. % IL-17A positivity was highest on CD15+ neutrophils, followed by mast cells and then CD4+T-cells. The number of IL-17A-secreting PMN cells significantly correlated with sublining CD68 expression (r = 0.618, p<0.01). IL-17A SF levels correlated with IL-6 SF levels (r = 0.675, p<0.01). Patients categorized according to tp0(2)< or >20 mmHg, showed those with low tp0(2)<20 mmHg had significantly higher IL-17A+ mononuclear cells with no difference observed for PMNs. Exposure of mononuclear and polymorphonuclear cells to 3% hypoxia, significantly induced IL-6 in mononuclear cells, but had no effect on IL-17A expression in mononuclear and polymorphonuclear cells.This study demonstrates IL-17A expression is localised to several immune cell subtypes within the inflamed synovial tissue, further supporting the concept that IL-17A is a key mediator in inflammatory arthritis. The association of hypoxia with Il-17A expression appears to be indirect, probably through hypoxia-induced pro-inflammatory pathways and leukocyte influx within the joint microenvironment

Interleukin-10 Promotes Pathological Angiogenesis by Regulating Macrophage Response to Hypoxia during Development

Aberrant angiogenesis in the eye is the most common cause of blindness. The current study examined the role of interleukin-10 (IL-10) in ischemia-induced pathological angiogenesis called neovascularization during postnatal development. IL-10 deficiency resulted in significantly reduced pathological retinal angiogenesis. In contrast to the choroicapillaris where IL-10 interferes with macrophage influx, IL-10 did not prevent anti-angiogenic macrophages from migrating to the retina in response to hypoxia. Instead, IL-10 promoted retinal angiogenesis by altering macrophage angiogenic function, as macrophages from wild-type mice demonstrated increased vascular endothelial growth factor (VEGF) and nitric oxide (NO) compared to IL-10 deficient macrophages. IL-10 appears to directly affect macrophage responsiveness to hypoxia, as macrophages responded to hypoxia with increased levels of IL-10 and STAT3 phosphorylation as opposed to IL-10 deficient macrophages. Also, IL-10 deficient macrophages inhibited the proliferation of vascular endothelial cells in response to hypoxia while wild-type macrophages failed to do so. These findings suggest that hypoxia guides macrophage behavior to a pro-angiogenic phenotype via IL-10 activated pathways

The Blazar TXS 0506+056 Associated with a High-energy Neutrino: Insights into Extragalactic Jets and Cosmic-Ray Acceleration

A neutrino with energy ∼290 TeV, IceCube-170922A, was detected in coincidence with the BL Lac object TXS 0506+056 during enhanced gamma-ray activity, with chance coincidence being rejected at ∼3σ level. We monitored the object in the very-high-energy (VHE) band with the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes for ∼41 hr from 1.3 to 40.4 days after the neutrino detection. Day-timescale variability is clearly resolved. We interpret the quasi-simultaneous neutrino and broadband electromagnetic observations with a novel one-zone lepto-hadronic model, based on interactions of electrons and protons co-accelerated in the jet with external photons originating from a slow-moving plasma sheath surrounding the faster jet spine. We can reproduce the multiwavelength spectra of TXS 0506+056 with neutrino rate and energy compatible with IceCube-170922A, and with plausible values for the jet power of . The steep spectrum observed by MAGIC is concordant with internal γγ absorption above ∼100 GeV entailed by photohadronic production of a ∼290 TeV neutrino, corroborating a genuine connection between the multi-messenger signals. In contrast to previous predictions of predominantly hadronic emission from neutrino sources, the gamma-rays can be mostly ascribed to inverse Compton upscattering of external photons by accelerated electrons. The X-ray and VHE bands provide crucial constraints on the emission from both accelerated electrons and protons. We infer that the maximum energy of protons in the jet comoving frame can be in the range ∼1014 – 1018 eV.Peer Reviewe